Recent advances in the development of new transgenic animal technology.

PubMed

Miao, Xiangyang

2013-03-01

Transgenic animal technology is one of the fastest growing biotechnology areas. It is used to integrate exogenous genes into the animal genome by genetic engineering technology so that these genes can be inherited and expressed by offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors in the production of transgenic animals. A variety of transgenic technologies are available. Each has its own advantages and disadvantages and needs further study because of unresolved technical and safety issues. Further studies will allow transgenic technology to explore gene function, animal genetic improvement, bioreactors, animal disease models, and organ transplantation. This article reviews the recently developed animal transgenic technologies, including the germ line stem cell-mediated method to improve efficiency, gene targeting to improve accuracy, RNA interference-mediated gene silencing technology, zinc-finger nuclease gene targeting technology and induced pluripotent stem cell technology. These new transgenic techniques can provide a better platform to develop transgenic animals for breeding new animal varieties and promote the development of medical sciences, livestock production, and other fields.

Regulatory Forum Opinion Piece*: Use and Utility of Animal Models of Disease for Nonclinical Safety Assessment: A Pharmaceutical Industry Survey.

PubMed

Morgan, Sherry J; Couch, Jessica; Guzzie-Peck, Peggy; Keller, Douglas A; Kemper, Ray; Otieno, Monicah A; Schulingkamp, Robert J; Jones, Thomas W

2017-04-01

An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies. The survey determined that the majority of companies used AMDs during drug discovery primarily as a means for proactively assessing potential nonclinical safety issues prior to the conduct of toxicology studies, followed closely by the use of AMDs to better understand toxicities associated with exaggerated pharmacology in traditional toxicology models or to derisk issues when the target is only expressed in the disease state. In contrast, the survey results indicated that the use of AMDs in development is infrequent, being used primarily to investigate nonclinical safety issues associated with targets expressed only in disease states and/or in response to requests from global regulatory authorities.

76 FR 60503 - Guidance for Industry on Target Animal Safety and Effectiveness Protocol Development and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... regarding how and when data collection forms and standard operating procedures should be included with the... topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or...

Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).

PubMed

Olson, Brian M; Bradley, Eric S; Sawicki, Thomas; Zhong, Weixiong; Ranheim, Erik A; Bloom, Jordan E; Colluru, Viswa T; Johnson, Laura E; Rekoske, Brian T; Eickhoff, Jens C; McNeel, Douglas G

2017-05-01

The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-throughput screening and small animal models, where are we?

PubMed Central

Giacomotto, Jean; Ségalat, Laurent

2010-01-01

Current high-throughput screening methods for drug discovery rely on the existence of targets. Moreover, most of the hits generated during screenings turn out to be invalid after further testing in animal models. To by-pass these limitations, efforts are now being made to screen chemical libraries on whole animals. One of the most commonly used animal model in biology is the murine model Mus musculus. However, its cost limit its use in large-scale therapeutic screening. In contrast, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the fish Danio rerio are gaining momentum as screening tools. These organisms combine genetic amenability, low cost and culture conditions that are compatible with large-scale screens. Their main advantage is to allow high-throughput screening in a whole-animal context. Moreover, their use is not dependent on the prior identification of a target and permits the selection of compounds with an improved safety profile. This review surveys the versatility of these animal models for drug discovery and discuss the options available at this day. PMID:20423335

USDA’s Corner

USDA-ARS?s Scientific Manuscript database

The 17a-methyltestosterone Target Animal Safety study with tilapia was completed early this summer and we are finalizing the QA audit with an ‘in-life study’ report. We are also assisting AADAP with compiling a draft of the Final Study Report for FDA. We will present findings with respect to acute...

Alternatives to in vivo Tests to Detect Endocrine Disrupting Chemicals (EDCs) in Fish and Amphibians

EPA Science Inventory

A significant amount of current research in risk assessment of chemicals is targeted to evaluate alternative test methods that may reduce, replace or refine the use of animals, while ensuring human and environmental health and safety. In 2009, the US EPA began implementation of t...

Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics.

PubMed

Vater, Axel; Klussmann, Sven

2015-01-01

Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three Spiegelmer candidates: emapticap pegol (NOX-E36; anti-CCL2), olaptesed pegol (NOX-A12; anti-CXCL12) and lexaptepid pegol (NOX-H94; anti-hepcidin), underwent regulatory safety studies, demonstrated good safety profiles in healthy volunteers and were taken into Phase IIa studies in patients. Proof-of-concept for emapticap pegol has recently been demonstrated in diabetic nephropathy patients. Furthermore, promising interim Phase IIa data of olaptesed pegol and lexapteptid pegol also suggest efficacy in the respective patient populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

9 CFR 113.41 - Calf safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Calf safety test. 113.41 Section 113.41 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.41 Calf safety test. The calf safety test provided in this section shall be conducted when...

9 CFR 113.45 - Sheep safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sheep safety test. 113.45 Section 113.45 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.45 Sheep safety test. The sheep safety test provided in this section shall be conducted when...

9 CFR 113.41 - Calf safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Calf safety test. 113.41 Section 113.41 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.41 Calf safety test. The calf safety test provided in this section shall be conducted when...

9 CFR 113.45 - Sheep safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sheep safety test. 113.45 Section 113.45 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.45 Sheep safety test. The sheep safety test provided in this section shall be conducted when...

The present and future of opioid analgesics in small animal practice.

PubMed

Simon, B T; Steagall, P V

2017-08-01

Opioids are the cornerstone for the treatment of acute pain in small animal patients. This is primarily because of their remarkable safety profile, high efficacy, and benefit of reversibility. There have been some significant advances in our knowledge on opioid pharmacology and clinical usage in companion animal medicine. This review discusses the progression of opioid use in small animal practice providing current misconceptions and controversies in light of routes of administration. Potential targets for research and drug development and novel therapies are discussed in addition to the concepts of glial cell modulators, individual variability, and opioid tolerance and hyperalgesia. The future brings an interesting perspective with the application of pharmacogenetics and individualized pain management in canine and feline practice. © 2016 John Wiley & Sons Ltd.

9 CFR 113.39 - Cat safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cat safety tests. 113.39 Section 113.39 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Seed Virus is tested for safety. (1) The test animals shall be determined to be susceptible to the...

Hazard identification and risk assessment for biologics targeting the immune system.

PubMed

Weir, Andrea B

2008-01-01

Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed with minimum risks to patients.

Animal-assisted interventions: A national survey of health and safety policies in hospitals, eldercare facilities, and therapy animal organizations.

PubMed

Linder, Deborah E; Siebens, Hannah C; Mueller, Megan K; Gibbs, Debra M; Freeman, Lisa M

2017-08-01

Animal-assisted intervention (AAI) programs are increasing in popularity, but it is unknown to what extent therapy animal organizations that provide AAI and the hospitals and eldercare facilities they work with implement effective animal health and safety policies to ensure safety of both animals and humans. Our study objective was to survey hospitals, eldercare facilities, and therapy animal organizations on their AAI policies and procedures. A survey of United States hospitals, eldercare facilities, and therapy animal organizations was administered to assess existing health and safety policies related to AAI programs. Forty-five eldercare facilities, 45 hospitals, and 27 therapy animal organizations were surveyed. Health and safety policies varied widely and potentially compromised human and animal safety. For example, 70% of therapy animal organizations potentially put patients at risk by allowing therapy animals eating raw meat diets to visit facilities. In general, hospitals had stricter requirements than eldercare facilities. This information suggests that there are gaps between the policies of facilities and therapy animal organizations compared with recent guidelines for animal visitation in hospitals. Facilities with AAI programs need to review their policies to address recent AAI guidelines to ensure the safety of animals and humans involved. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Examining the nexus between domestic violence and animal abuse in a national sample of service providers.

PubMed

Krienert, Jessie L; Walsh, Jeffrey A; Matthews, Kevin; McConkey, Kelly

2012-01-01

Companion animals play a complex role in families impacted by violence. An outlet of emotional support for victims, the family pet often becomes a target for physical abuse. Results from a comprehensive e-survey of domestic violence shelters nationwide (N = 767) highlight both improvements and existing gaps in service provision for domestic violence victims and their pets. Quantitative and qualitative data noted frequently encountered obstacles to successful shelter seeking by abuse victims with companion animals including a lack of availability, funding, space, and reliable programming. Although results indicate an overall improvement in organizational awareness, fewer than half of surveyed shelters include intake questions about animals. Continued awareness and an expansion of services is needed to create viable safety planning strategies and reliable alternatives for women with companion animals in order to improve the likelihood that abuse victims will seek escape and refuge for themselves, their children, and their pets.

Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

PubMed

Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

2017-11-01

The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice.

PubMed

DeTolla, L; Sanchez, R; Khan, E; Tyler, B; Guarnieri, M

2014-01-01

Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine.

Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

PubMed Central

DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

2014-01-01

Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

Investigation of nutriactive phytochemical - gamma-oryzanol in experimental animal models.

PubMed

Szcześniak, K A; Ostaszewski, P; Ciecierska, A; Sadkowski, T

2016-08-01

Gamma-oryzanol (GO) is an abundant dietary antioxidant that is considered to have beneficial effects in cardiovascular disease, cancer and diabetes. Other potential properties of GO include inhibition of gastric acid secretion and decreased post-exercise muscle fatigue. GO is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil, a byproduct of rice processing. GO has been studied by many researchers over the last three decades. In particular, the utility of GO supplementation has been documented in numerous animal models. A large variety of species was examined, and various experimental methodologies and targets were applied. The aim of this study was to summarize the body of research on GO supplementation in animals and to examine possible mechanisms of GO action. Furthermore, while the safety of GO supplementation in animals has been well documented, studies demonstrating pharmacokinetics, pharmacodynamics and efficiency are less clear. The observed differences in these findings are also discussed. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Estimation of concentration of radionuclides in skeletal muscle from blood, based on the data from abandoned animals in Fukushima.

PubMed

Fukuda, Tomokazu

2018-06-01

The damage caused by the earthquake on 11 March, 2011 resulted in a serious nuclear accident in Japan. Due to the damage to the Fukushima Daiichi Nuclear Power Plant (FNPP), large amounts of radioactive substances were released into the environment. In particular, one of the largest safety concerns is radioactive cesium ( 134 Cs and 137 Cs). Due to the FNPP nuclear accident, a 20 km area was restricted from human activity, and various types of domestic animals were left in the zone. We collected the organs and tissues from sacrificed animals to obtain scientific data to evaluate the internal deposition of radioactive compounds. At first, we found there is a strong correlation between blood 137 Cs and organ 137 Cs with data from 44 cattle, indicating that skeletal muscle is the target organ of deposition of radioactive cesium. Second, we analyzed the relationship between blood 137 Cs and muscle 137 Cs within relatively lower radioactive concentration, suggesting that estimation of concentration of 137 Cs is possible from blood concentration of 137 Cs. Finally, we developed computer software to estimate the muscle 137 Cs concentration from blood samples. Our study contributes to the food safety of livestock products. © 2018 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

9 CFR 390.7 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Appeals. 390.7 Section 390.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... (departmental regulations, 7 CFR 1.14) and addressed as follows: Administrator, Food Safety and Inspection...

9 CFR 392.5 - Filing procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Filing procedures. 392.5 Section 392.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND..., Food Safety and Inspection Service, Room 2534 South Building, 1400 Independence Ave., SW., Washington...

[New advances in animal transgenic technology].

PubMed

Sun, Zhen-Hong; Miao, Xiang-Yang; Zhu, Rui-Liang

2010-06-01

Animal transgenic technology is one of the fastest growing biotechnology in the 21st century. It is used to integrate foreign genes into the animal genome by genetic engineering technology so that foreign genes can be expressed and inherited to the offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors on preparation of transgenic animals. A variety of transgenic techniques are available, each of which has its own advantages and disadvantages and still needs further study because of unresolved technical and safety issues. With the in-depth research, the transgenic technology will have broad application prospects in the fields of exploration of gene function, animal genetic improvement, bioreactor, animal disease models, organ transplantation and so on. This article reviews the recently developed animal gene transfer techniques, including germline stem cell mediated method to improve the efficiency, gene targeting to improve the accuracy, RNA interference (RNAi)-mediated gene silencing technology, and the induced pluripotent stem cells (iPS) transgenic technology. The new transgenic techniques can provide a better platform for the study of trans-genic animals and promote the development of medical sciences, livestock production, and other fields.

The role of veterinary services in animal health and food safety surveillance, and coordination with other services.

PubMed

Bellemain, V

2013-08-01

The control of animal health and food safety has undergone profound changes and is now seen in terms of a global approach, 'from the stable to the table'. The risks themselves have also evolved, principally due to changing practices, and this, coupled with increased knowledge and changes in consumer demands, has led to a more global conception of production chains. In terms of official controls, targeted control of the final food product has gradually been replaced by control of the production processes and an integrated approach to hazards throughout the production chain. This, in turn, has resulted in a new division of responsibilities among the producers (farmers), the manufacturers and the administration; namely, Veterinary Services. The areas in which veterinarians are involved have gradually been extended from animal production to all levels of the food production chain. Animal health interventions on farms are comparable to interventions in agri-food companies. Both are, or should be, included in veterinary training and education. To meet new challenges, the current trend is for Veterinary Services to be responsible for, or coordinate, sanitary interventions from the stable to the table. Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of the resources available.

9 CFR 392.1 - Scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scope and purpose. 392.1 Section 392.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... contains provisions governing the submission of petitions for rulemaking to the Food Safety and Inspection...

Canadian regulatory requirements for recombinant fish vaccines.

PubMed

Sethi, M S; Gifford, G A; Samagh, B S

1997-01-01

In Canada, veterinary biological products derived by using conventional and new techniques of biotechnology are licensed and regulated under the Health of Animals Act and Regulations. Biological products include vaccines, bacterins, bacterin-toxoids and diagnostic kits which are used for the prevention, treatment or diagnosis of infectious diseases in all species of animals, including fish. Veterinary biologicals are licensed on the basis of fulfillment of four criteria: purity, potency, safety and efficacy. A risk-based approach is used to evaluate the safety of the product in target species, as well as non-target species, humans and the environment. On the basis of biological characteristics, biotechnology derived veterinary biologicals have been divided into two broad categories, high and low risk products. The paper describes the regulatory framework for the licensing of veterinary biologicals in Canada, with emphasis on the regulatory considerations for recombinant fish vaccines. Stages of movement of the product from research in a contained laboratory facility to a fully licensed product for free sale are discussed. The requirements for field testing and environmental assessment involved in these stages are highlighted. Manufacturers and researchers who intend to commercialize experimental vaccines are encouraged to consult with the Veterinary Biologics and Biotechnology Section early in the product development process so that the research data and quality assurance documentation are consistent with regulatory requirements.

Animal-Assisted Interventions in Dutch Nursing Homes: A Survey.

PubMed

Schuurmans, Lonneke; Enders-Slegers, Marie-Jose; Verheggen, Theo; Schols, Jos

2016-07-01

Animal-assisted interventions (AAI) have become more and more popular in nursing homes in the past decade. Various initiatives for using animals in nursing homes have been developed over the years (eg, animal visiting programs, residential companion animals, petting zoos) and, on the whole, the number of nursing homes that refuse animals on their premises has declined. In this survey, we aimed to determine how many Dutch nursing homes offer AAIs, what type of interventions are used, and with what aim. We also focus on the use of underlying health, hygiene, and (animal) safety protocols. Using an online Dutch nursing home database, we invited all listed (457) nursing home organizations in the Netherlands (encompassing a total of 804 nursing home locations) to participate in our digital survey, powered by SurveyMonkey. The survey consisted of a total of 45 questions, divided into general questions about the use of animals in interventions; the targeted client population(s); and specific questions about goals, guidelines, and protocols. The results were analyzed with SPSS Statistics. In the end, 244 surveys, representing 165 organizations, were returned: 125 nursing homes used AAI in one way or another, 40 did not. Nursing homes that did not offer AAI cited allergy and hygiene concerns as the most important reasons. Most nursing homes offering AAI used visiting animals, mostly dogs (108) or rabbits (76). A smaller number of nursing homes had resident animals, either living on the ward or in a meadow outside. Almost all programs involved animal-assisted activities with a recreational purpose; none of the participating nursing homes provided animal assisted therapy with therapeutic goals. Psychogeriatric patients were most frequently invited to participate. A total of 88 nursing homes used alternatives when animals were not an option or not available. The most popular alternative was the use of stuffed animals (83) followed by FurReal Friends robotic toys (14). The sophisticated robot seal Paro was used in 7 nursing homes. A large percentage (80%) of nursing homes that worked with animals did not have AAI-specific health protocols or animal welfare and safety protocols underlying the animal activities or specific selection criteria for the selection of suitable animals. Most of the participating Dutch nursing homes offer AAI in recreational programs (animal-assisted activities) for psychogeriatric clients (using visiting animals, especially dogs). Most nursing homes do not have specific AAI protocols for animal welfare, hygiene, and safety during animal activities, nor do they employ specific selection criteria for participating animals and their handlers. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 390.1 - Scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scope and purpose. 390.1 Section 390.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... November 1, 1996, of the Food Safety and Inspection Service (FSIS), and the procedures by which the public...

Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle.

PubMed

Barrera, J; Brake, D A; Kamicker, B J; Purcell, C; Kaptur, R; Schieber, T; Lechtenberg, K; Miller, T D; Ettyreddy, D; Brough, D E; Butman, B T; Colby, M; Neilan, J G

2018-04-01

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements. © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Risk assessment of coccidostatics during feed cross-contamination: animal and human health aspects.

PubMed

Dorne, J L C M; Fernández-Cruz, M L; Bertelsen, U; Renshaw, D W; Peltonen, K; Anadon, A; Feil, A; Sanders, P; Wester, P; Fink-Gremmels, J

2013-08-01

Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. Eleven different coccidiostats are licensed in the EU for the prevention of coccidiosis in these animal species. According to their chemical nature and main biological activity, these compounds can be grouped as ionophoric (monensin, lasalocid sodium, salinomycin, narasin, maduramicin and semduramicin) or non-ionophoric (robenidine, decoquinate, nicarbazin, diclazuril, and halofuginone) substances. Coccidiostats are used as feed additives, mixed upon request into the compounded feed. During the technical process of commercial feed production, cross-contamination of feed batches can result in the exposure of non-target animals and induce adverse health effects in these animals due to a specific sensitivity of mammalian species as compared to poultry. Residue formation in edible tissues of non-target species may result in unexpected human exposure through the consumption of animal products. This review presents recent risk assessments performed by the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). The health risk to non-target species that would result from the consumption of cross-contaminated feed with coccidostats at levels of 2, 5 or 10% was found to be negligible for most animal species with the exception of salinomycin and monensin in horses because of the particular sensitivity for which toxicity may occur when cross-contamination exceeds 2% and 5% respectively. Kinetic data and tissue analyses showed that residues of coccidiostats may occur in the liver and eggs in some cases. However, the level of residues of each coccidiostat in edible animal tissues remained sufficiently low that the aggregate exposure of consumers would not exceed the established acceptable daily intake (ADI) of each coccidiostat. It could be concluded that technical cross-contamination of animal feeds would not be expected to adversely affect the health of consumers. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk assessment of coccidostatics during feed cross-contamination: Animal and human health aspects

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

Dorne, J.L.C.M., E-mail: jean-lou.dorne@efsa.europa.eu; Fernández-Cruz, M.L.; Bertelsen, U.

Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. Eleven different coccidiostats are licensed in the EU for the prevention of coccidiosis in these animal species. According to their chemical nature and main biological activity, these compounds can be grouped as ionophoric (monensin, lasalocid sodium, salinomycin, narasin, maduramicin and semduramicin) or non-ionophoric (robenidine, decoquinate, nicarbazin, diclazuril, and halofuginone) substances. Coccidiostats are used as feed additives, mixed upon request into the compounded feed. During the technical process of commercial feed production, cross-contamination of feed batches can result in the exposure of non-target animals and induce adversemore » health effects in these animals due to a specific sensitivity of mammalian species as compared to poultry. Residue formation in edible tissues of non-target species may result in unexpected human exposure through the consumption of animal products. This review presents recent risk assessments performed by the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). The health risk to non-target species that would result from the consumption of cross-contaminated feed with coccidostats at levels of 2, 5 or 10% was found to be negligible for most animal species with the exception of salinomycin and monensin in horses because of the particular sensitivity for which toxicity may occur when cross-contamination exceeds 2% and 5% respectively. Kinetic data and tissue analyses showed that residues of coccidiostats may occur in the liver and eggs in some cases. However, the level of residues of each coccidiostat in edible animal tissues remained sufficiently low that the aggregate exposure of consumers would not exceed the established acceptable daily intake (ADI) of each coccidiostat. It could be concluded that technical cross-contamination of animal feeds would not be expected to adversely affect the health of consumers.« less

The commercial impact of pig Salmonella spp. infections in border-free markets during an economic recession

PubMed Central

Evangelopoulou, G.; Kritas, S.; Christodoulopoulos, G.; Burriel, A. R.

2015-01-01

The genus Salmonella, a group of important zoonotic pathogens, is having global economic and political importance. Its main political importance results from the pathogenicity of many of its serovars for man. Serovars Salmonella Enteritidis and Salmonella Typhimurium are currently the most frequently associated to foodborne infections, but they are not the only ones. Animal food products contaminated from subclinically infected animals are a risk to consumers. In border free markets, an example is the EU, these consumers at risk are international. This is why, economic competition could use the risk of consumer infection either to restrict or promote free border trade in animals and their products. Such use of public health threats increases during economic recessions in nations economically weak to effectively enforce surveillance. In free trade conditions, those unable to pay the costs of pathogen control are unable to effectively implement agreed regulations, centrally decided, but leaving their enforcement to individual states. Free trade of animal food products depends largely on the promotion of safety, included in “quality,” when traders target foreign markets. They will overtake eventually the markets of those ineffectively implementing agreed safety regulations, if their offered prices are also attractive for recession hit consumers. Nations unable to effectively enforce safety regulations become disadvantaged partners unequally competing with producers of economically robust states when it comes to public health. Thus, surveillance and control of pathogens like Salmonella are not only quantitative. They are also political issues upon which states base national trade decisions. Hence, the quantitative calculation of costs incurring from surveillance and control of animal salmonelloses, should not only include the cost for public health protection, but also the long term international economic and political costs for an individual state. These qualitative and qualitative costs of man and animal Salmonella infections should be calculated in the light of free trade and open borders. Understandably, accurate calculation of the economic and political costs requires knowledge of the many factors influencing nationally the quality and safety of pork products and internationally free trade. Thus, how Salmonella pig infections affect commerce and public health across open borders depends on a state’s ability to accurately calculate costs for the surveillance and control of animal salmonelloses in general, and pig infections as a particular example. PMID:27047083

MicroRNAs: New Players in Anesthetic-Induced Developmental Neurotoxicity

PubMed Central

Twaroski, Danielle; Bosnjak, Zeljko J.; Bai, Xiaowen

2015-01-01

Growing evidence demonstrates that prolonged exposure to general anesthetics during brain development induces widespread neuronal cell death followed by long-term memory and learning disabilities in animal models. These studies have raised serious concerns about the safety of anesthetic use in pregnant women and young children. However, the underlying mechanisms of anesthetic-induced neurotoxicity are complex and are not well understood. MicroRNAs are endogenous, small, non-coding RNAs that have been implicated to play important roles in many different disease processes by negatively regulating target gene expression. A possible role for microRNAs in anesthetic-induced developmental neurotoxicity has recently been identified, suggesting that microRNA-based signaling might be a novel target for preventing the neurotoxicity. Here we provide an overview of anesthetic-induced developmental neurotoxicity and focus on the role of microRNAs in the neurotoxicity observed in both human stem cell-derived neuron and animal models. Aberrant expression of some microRNAs has been shown to be involved in anesthetic-induced developmental neurotoxicity, revealing the potential of microRNAs as therapeutic or preventive targets against the toxicity. PMID:26146587

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells?

PubMed

Hombach, Andreas A; Abken, Hinrich

2017-02-01

Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30 + hematopoietic stem and progenitor cells while eliminating CD30 + lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

PubMed

Guarnieri, M; Brayton, C; Sarabia-Estrada, R; Tyler, B; McKnight, P; DeTolla, L

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

PubMed Central

Brayton, C.; Sarabia-Estrada, R.; McKnight, P.; DeTolla, L.

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy. PMID:28492060

[Preclinical evaluation of the safety of biotechnology products: specific aspects].

PubMed

Descotes, Jacques; Ravel, Guillaume; Vial, Thierry

2003-01-01

Biotechnology-derived products represent a class of increasingly numerous drugs. One of their major characteristics is extreme diversity, which requires specific approaches for the preclinical evaluation of their safety. The selection of relevant animal species is not easy, as most of these products are human-specific. Thus, only one species will often be used, i.e. primates. As most of these products are large molecules, they can be directly immunogenic. When they are human-specific, no animal model is available to predict the risk. Many biotechnology-derived products have an expected influence on the immune system. This must be taken into account in the preclinical strategy of immunotoxicity evaluation that is now required for every new drug. As conventional toxicity testing is generally limited, safety pharmacology studies should include more than the core battery of assays required by current guidelines in order to complement missing data as much as possible. Because of these particularities, a comprehensive investigation of metabolism and pharmacokinetics is not usually needed. Some products can cross-react with cellular components not intended as therapeutic targets. It is, therefore, essential to rule out the risk of possible cross-reactions that can result in adverse effects. Finally, viral safety is a crucial component of the preclinical safety evaluation of these products. Overall, biotechnology-derived products raise specific issues because of their innovative and original characteristics, and it is difficult to address all these issues if not by using a case-by-case approach.

Potential large animal models for gene therapy of human genetic diseases of immune and blood cell systems.

PubMed

Bauer, Thomas R; Adler, Rima L; Hickstein, Dennis D

2009-01-01

Genetic mutations involving the cellular components of the hematopoietic system--red blood cells, white blood cells, and platelets--manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease.

A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals.

PubMed

Hur, Sun Jin

2017-10-01

The author widely surveyed and analyzed the food safety issues, ethical issues, permits, and approval of animal products from animals cloned by somatic cell nuclear transfer worldwide. As a result of a 2-year survey, the author found that there is no evidence that meat and milk derived from cloned animals or their progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive effects, or allergic reactions. Most countries have not approved meat and milk derived from cloned animals, and their progeny are entering the food supply. To establish the guidelines, the author suggests four principles of safety assessment for meat and milk derived from cloned animals. The four main principles for safety assessment are similarities of chemical composition, adverse reproductive effects, genotoxicity, and allergic reactions under the influence of meat and milk from cloned animals and noncloned counterparts. This principle means that meat and milk derived from a cloned animal are safe if there are no differences in the four safety assessments of meat and milk between cloned animal's progeny and noncloned counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety of fenbendazole in common peafowl (Pavo cristatus).

PubMed

Umar, Sajid; Abbas, Seema; Khan, Muhammad Irfan; Nisa, Qamarun; Younus, Muhammad; Aqil, Kiran; Qayyum, Rizwan; Yaqoob, Muhammad; Ali, Asif; Yaseen, Muhammad Asif; Shah, Muhammad Ali

2018-01-01

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.

76 FR 16795 - The National Antimicrobial Resistance Monitoring System Strategic Plan 2011-2015; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

....fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/default.htm , http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm062630.htm , http://www.fda.gov/AnimalVeterinary/Safety...

Development of a Salmonella cross-protective vaccine for food animal production systems.

PubMed

Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

2015-01-01

Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Verstraete, Frans, E-mail: Frans.Verstraete@ec.europa.eu

Directive 2002/32/EC of 7 May 2002 of the European Parliament and of the Council on undesirable substances in animal feed is the framework for the EU action on undesirable substances in feed. This framework Directive provides: ⁎that products intended for animal feed may enter for use in the Union from third countries, be put into circulation and/or used in the Union only if they are sound, genuine and of merchantable quality and therefore when correctly used do not represent any danger to human health, animal health or to the environment or could adversely affect livestock production. ⁎that in order tomore » protect animal and public health and the environment, maximum levels for specific undesirable substances shall be established where necessary. ⁎for mandatory consultation of a scientific body (EFSA) for all provisions which may have an effect upon public health or animal health or on the environment. ⁎that products intended for animal feed containing levels of an undesirable substance that exceed the established maximum level may not be mixed for dilution purposes with the same, or other, products intended for animal feed and may not be used for the production of compound feed. Based on the provisions and principles laid down in this framework Directive, maximum levels for a whole range of undesirable substances have been established at EU level. During the discussions in view of the adoption of Directive 2002/32/EC, the European Commission made the commitment to review all existing provisions on undesirable substances on the basis of updated scientific risk assessments. Following requests of the European Commission, the Panel on Contaminants in the Food Chain (CONTAM) from the European Food Safety Authority (EFSA) has completed a series of 30 risk assessments undertaken over the last 5 years on undesirable substances in animal feed reviewing the possible risks for animal and human health due to the presence of these substances in animal feed. EU legislation on undesirable substances has undergone recently several changes to take account of these most recent scientific opinions. Furthermore EFSA has assessed the risks for public and animal health following the unavoidable carry-over of coccidiostats into non target feed. Maximum levels for the unavoidable carry-over have been established for the non-target feed and the food of animal origin from non-target animal species.« less

Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

PubMed

Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

2012-03-01

Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

Agency perspectives on food safety for the products of animal biotechnology.

PubMed

Howard, H J; Jones, K M; Rudenko, L

2012-08-01

Animal biotechnology represents one subset of tools among a larger set of technologies for potential use to meet increasing world demands for food. Assisted reproductive technologies (ART) such as artificial insemination and embryo transfer continue to make positive contributions in food animal production. The US Food and Drug Administration (FDA) performed a comprehensive risk assessment to identify potential food consumption or animal health risks associated with animal cloning, an emerging ART. At that time, FDA concluded that animal cloning posed no unique risks either to animal health or to food consumption, and food from animal clones and their sexually reproduced offspring required no additional federal regulation beyond that applicable to conventionally bred animals of the species examined. At this time, no new information has arisen that would necessitate a change in FDA's conclusions on food from animal clones or their sexually reproduced offspring. Use of recombinant DNA technologies to produce genetically engineered (GE) animals represents another emerging technology with potential to impact food animal production. In its regulation of GE animals, FDA follows a cumulative, risk-based approach to address scientific questions related to the GE animals. FDA evaluates data and information on the safety, effectiveness and stability of the GE event. FDA carries out its review at several levels (e.g. molecular biology, animal safety, food safety, environmental safety and claim validation). GE animal sponsors provide data to address risk questions for each level. This manuscript discusses FDA's role in evaluation of animal cloning and GE animals. © 2012 Blackwell Verlag GmbH.

Veterinary pharmacovigilance in India: A need of hour.

PubMed

Kumar, Rishi; Kalaiselvan, Vivekanandan; Verma, Ravendra; Kaur, Ismeet; Kumar, Pranay; Singh, G N

2017-01-01

Veterinary pharmacovigilance (PV) is important for the Medicine which are used for treating disease in animals. It becomes more important when these animals are further used for producing food. Adverse drug reactions (ADRs) have a direct impact on animals and indirect impact on human beings, for example, through milk products, other animal producing food products. Currently, PV program of India is playing a vital role in assessing the safety of medicines in Indian Population. The safety of medicine in animals can be assessed by veterinary PV. The research institutes involved in animal research and veterinary hospitals can be considered as ADR monitoring centers to assess the safety of medicines on animals.

In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

PubMed Central

Lau, Cia-Hin; Suh, Yousin

2017-01-01

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics. PMID:29333255

21 CFR 522.2476 - Trenbolone acetate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... breeding or in dairy animals. Safety and effectiveness have not been established in veal calves. A... animals intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been...

21 CFR 522.2476 - Trenbolone acetate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... breeding or in dairy animals. Safety and effectiveness have not been established in veal calves. A... animals intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been...

21 CFR 522.2476 - Trenbolone acetate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... breeding or in dairy animals. Safety and effectiveness have not been established in veal calves. A... animals intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been...

21 CFR 522.2476 - Trenbolone acetate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... breeding or in dairy animals. Safety and effectiveness have not been established in veal calves. A... animals intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been...

21 CFR 522.2476 - Trenbolone acetate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... breeding or in dairy animals. Safety and effectiveness have not been established in veal calves. A... animals intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been...

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo.

PubMed

Altenburg, Arwen F; van de Sandt, Carolien E; Li, Bobby W S; MacLoughlin, Ronan J; Fouchier, Ron A M; van Amerongen, Geert; Volz, Asisa; Hendriks, Rudi W; de Swart, Rik L; Sutter, Gerd; Rimmelzwaan, Guus F; de Vries, Rory D

2017-08-17

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.

New frontiers in gene targeting and cloning: success, application and challenges in domestic animals and human embryonic stem cells.

PubMed

Denning, Chris; Priddle, Helen

2003-07-01

Until recently, precise modification of the animal genome by gene targeting was restricted to the mouse because germline competent embryonic stem cells are not available in any other mammalian species. Nuclear transfer (NT) technology now provides an alternative route for cell-based transgenesis in domestic species, offering new opportunities in genetic modification. Livestock that produce human therapeutic proteins in their milk, have organs suitable for xenotransplantation, or that could provide resistance to diseases such as spongiform encephalopathies have been produced by NT from engineered, cultured somatic cells. However, improvements in the efficiency of somatic cell gene targeting and a greater understanding of the reprogramming events that occur during NT are required for the routine application of what is currently an inefficient process. The ability to reprogramme and genetically manipulate cells will also be crucial for full exploitation of human embryonic stem (hES) cells, which offer unparalleled opportunities in human health and biotechnology. Particularly pertinent are directed differentiation of hES lines to specific cell lineages, production of cells that evade the patient's immune system and ensuring the safety of ensuing transplants. This review will discuss some of the successes, applications and challenges facing gene targeting in livestock and hES cells.

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

PubMed

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

A Template Analysis of Intimate Partner Violence Survivors' Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention.

PubMed

Collins, Elizabeth A; Cody, Anna M; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R; Williams, James Herbert

2018-03-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors' health and safety.

A Template Analysis of Intimate Partner Violence Survivors’ Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention

PubMed Central

Collins, Elizabeth A.; Cody, Anna M.; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R.; Williams, James Herbert

2018-01-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors’ health and safety. PMID:29332521

77 FR 38751 - Codification of Animal Testing Policy

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

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

9 CFR 392.3 - Required information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Required information. 392.3 Section 392.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.3 Required...

9 CFR 392.7 - Comments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Comments. 392.7 Section 392.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.7 Comments. (a) Any interested...

9 CFR 391.4 - Laboratory services rate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Laboratory services rate. 391.4 Section 391.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES...

9 CFR 391.5 - Laboratory accreditation fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Laboratory accreditation fees. 391.5 Section 391.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES...

Transgenic maize event TC1507: Global status of food, feed, and environmental safety

PubMed Central

Baktavachalam, Gajendra B; Delaney, Bryan; Fisher, Tracey L; Ladics, Gregory S; Layton, Raymond J; Locke, Mary EH; Schmidt, Jean; Anderson, Jennifer A; Weber, Natalie N; Herman, Rod A; Evans, Steven L

2015-01-01

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-Ø15Ø7–1) or the Herculex®# I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued. PMID:26018138

Transgenic maize event TC1507: Global status of food, feed, and environmental safety.

PubMed

Baktavachalam, Gajendra B; Delaney, Bryan; Fisher, Tracey L; Ladics, Gregory S; Layton, Raymond J; Locke, Mary Eh; Schmidt, Jean; Anderson, Jennifer A; Weber, Natalie N; Herman, Rod A; Evans, Steven L

2015-01-01

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-Ø15Ø7-1) or the Herculex®(#) I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued.

A perspective on the safety of cosmetic products: a position paper of the American Council on Science and Health.

PubMed

Ross, Gilbert

2006-01-01

Over the years, some activist groups have targeted cosmetics as possible human health threats, claiming that cosmetic ingredients are not adequately tested for safety and may pose risks to consumers. The groups allege that industry practices related to safety testing are flawed, that there is little government oversight, and that cosmetics contain cancer-causing chemicals and other toxicants. A critical review of the scientific data related to these claims indicates the following: (1) Industry has the primary responsibility to ensure that all ingredients, preservatives, and coformulants used in products are safe for their intended uses. (2) The U.S. Food and Drug Administration (FDA) has regulatory oversight of the cosmetic industry. Its authority includes the banning or restriction of ingredients for safety reasons. (3) The Cosmetic Ingredient Review (CIR), an independent, scientific review board, critically evaluates chemical ingredients used in cosmetics and publishes the results of its findings in the peer-reviewed literature. (4) Health-related allegations about cosmetic ingredients are generally based on the results of high-dose laboratory testing in animals and have little relevance for humans. As true now as when Paracelsus said it in the 16th century, "It is the dose that makes the poison." (5) The health-related allegations involving specific chemicals (e.g., phthalates, parabens, and 1,3-butadiene) fail to consider important scientific studies and recent regulatory conclusions about these chemicals, which have found that they are not hazardous. (6) Animal and human physiology differ in crucial ways, further invalidating simplistic attempts to extrapolate rodent testing to human health risks. The cosmetic industry should be encouraged to publish more of its toxicity studies and safety evaluations, which would aid in dispelling the uncertainty that some consumers have about cosmetic safety.

9 CFR 113.39 - Cat safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Cat safety tests. 113.39 Section 113... Procedures § 113.39 Cat safety tests. The safety tests provided in this section shall be conducted when... recommended for use in cats. (a) The cat safety test provided in this paragraph shall be used when the Master...

The new Israeli feed safety law: challenges in relation to animal and public health.

PubMed

Barel, Shimon; Elad, Dani; Cuneah, Olga; Shimshoni, Jakob A

2017-03-01

The Israeli feed safety legislation, which came to prominence in the early 1970s, has undergone a major change from simple feed safety and quality regulations to a more holistic concept of control of feed safety and quality throughout the whole feed production chain, from farm to the end user table. In February 2014, a new law was approved by the Israeli parliament, namely the Control of Animal Feed Law, which is expected to enter into effect in 2017. The law is intended to regulate the production and marketing of animal feed, guaranteeing the safety and quality of animal products throughout the production chain. The responsibility on the implementation of the new feed law was moved from the Plant Protection Inspection Service to the Veterinary Services and Animal Health. In preparation for the law's implementation, we have characterized the various sources and production lines of feed for farm and domestic animals in Israel and assessed the current feed safety challenges in terms of potential hazards or undesirable substances. Moreover, the basic requirements for feed safety laboratories, which are mandatory for analyzing and testing for potential contaminants, are summarized for each of the contaminants discussed. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

9 CFR 392.8 - Expedited review.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... health by removing or reducing foodborne pathogens or other potential food safety hazards that might be... reduce or remove foodborne pathogens or other potential food safety hazards that are likely to be present...

9 CFR 300.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Purpose. 300.1 Section 300.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... of the Food Safety and Inspection Service (FSIS), an agency of the United States Department of...

9 CFR 391.1 - Scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scope and purpose. 391.1 Section 391.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY...

9 CFR 390.8 - Agency response to requests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Agency response to requests. 390.8 Section 390.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC...

9 CFR 592.10 - Authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Authority. 592.10 Section 592.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... this part. The Food Safety Inspection Service and its officers and employees shall not be liable in...

9 CFR 392.6 - Public display.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Public display. 392.6 Section 392.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.6 Public display. (a) All...

9 CFR 300.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Purpose. 300.1 Section 300.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... of the Food Safety and Inspection Service (FSIS), an agency of the United States Department of...

9 CFR 390.6 - Fee schedule.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Fee schedule. 390.6 Section 390.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.6 Fee...

9 CFR 391.3 - Overtime and holiday rate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Overtime and holiday rate. 391.3 Section 391.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES...

9 CFR 392.2 - Definition of petition.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Definition of petition. 392.2 Section 392.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.2 Definition of...

Reduced salmonella fecal shedding in swine administered porcine granulocyte-colony stimulating factor (G-CSF)

USDA-ARS?s Scientific Manuscript database

Salmonella colonization of food animals is a concern for animal health, food safety and public health. Key objectives of pre-harvest food safety programs are to detect asymptomatic Salmonella carriage in food animals, reduce colonization, and prevent transmission of Salmonella to other animals and ...

9 CFR 392.9 - Availability of additional guidance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Availability of additional guidance. 392.9 Section 392.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.9 Availability of additional guidance....

9 CFR 392.9 - Availability of additional guidance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Availability of additional guidance. 392.9 Section 392.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.9 Availability of additional guidance....

9 CFR 390.2 - Published materials.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Published materials. 390.2 Section 390.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.2 Published materials. FSIS rules and...

9 CFR 390.2 - Published materials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Published materials. 390.2 Section 390.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.2 Published materials. FSIS rules and...

9 CFR 390.3 - Indexes, reference guide, and handbook.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Indexes, reference guide, and handbook. 390.3 Section 390.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC...

9 CFR 390.2 - Published materials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Published materials. 390.2 Section 390.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.2 Published materials. FSIS rules and...

9 CFR 392.9 - Availability of additional guidance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Availability of additional guidance. 392.9 Section 392.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.9 Availability of additional guidance....

9 CFR 391.5 - Laboratory accreditation fees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Laboratory accreditation fees. 391.5 Section 391.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.5...

9 CFR 391.5 - Laboratory accreditation fees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Laboratory accreditation fees. 391.5 Section 391.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.5...

9 CFR 390.2 - Published materials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Published materials. 390.2 Section 390.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.2 Published materials. FSIS rules and...

9 CFR 391.5 - Laboratory accreditation fees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Laboratory accreditation fees. 391.5 Section 391.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.5...

9 CFR 391.5 - Laboratory accreditation fees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Laboratory accreditation fees. 391.5 Section 391.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.5...

9 CFR 392.9 - Availability of additional guidance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Availability of additional guidance. 392.9 Section 392.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.9 Availability of additional guidance....

Application of Model Animals in the Study of Drug Toxicology

NASA Astrophysics Data System (ADS)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

PubMed

Marx, Tennille K; Glávits, Róbert; Endres, John R; Palmer, Philip A; Clewell, Amy E; Murbach, Timothy S; Hirka, Gábor; Pasics, Ilona

2016-11-01

Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2016.

Microbiological Safety of Animal Wastes Processed by Physical Heat Treatment: An Alternative To Eliminate Human Pathogens in Biological Soil Amendments as Recommended by the Food Safety Modernization Act.

PubMed

Chen, Zhao; Jiang, Xiuping

2017-03-01

Animal wastes have high nutritional value as biological soil amendments of animal origin for plant cultivation in sustainable agriculture; however, they can be sources of some human pathogens. Although composting is an effective way to reduce pathogen levels in animal wastes, pathogens may still survive under certain conditions and persist in the composted products, which potentially could lead to fresh produce contamination. According to the U.S. Food and Drug Administration Food Safety Modernization Act, alternative treatments are recommended for reducing or eliminating human pathogens in raw animal manure. Physical heat treatments can be considered an effective method to inactivate pathogens in animal wastes. However, microbial inactivation in animal wastes can be affected by many factors, such as composition of animal wastes, type and physiological stage of the tested microorganism, and heat source. Following some current processing guidelines for physical heat treatments may not be adequate for completely eliminating pathogens from animal wastes. Therefore, this article primarily reviews the microbiological safety and economic value of physically heat-treated animal wastes as biological soil amendments.

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity.

PubMed

Amacher, David E

2010-05-15

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other "omics" technologies can provide added selectivity and sensitivity in preclinical drug safety testing.

Safety of Microbubbles and Transcranial Ultrasound in Rabbits

NASA Astrophysics Data System (ADS)

Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

2007-05-01

The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

Role of Animal Models in Coronary Stenting.

PubMed

Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

2016-02-01

Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

Can stress in farm animals increase food safety risk?

PubMed

Rostagno, Marcos H

2009-09-01

All farm animals will experience some level of stress during their lives. Stress reduces the fitness of an animal, which can be expressed through failure to achieve production performance standards, or through disease and death. Stress in farm animals can also have detrimental effects on the quality of food products. However, although a common assumption of a potential effect of stress on food safety exists, little is actually known about how this interaction may occur. The aim of this review was to examine the current knowledge of the potential impact of stress in farm animals on food safety risk. Colonization of farm animals by enteric pathogens such as Escherichia coli O157:H7, Salmonella, and Campylobacter, and their subsequent dissemination into the human food chain are a major public health and economic concern for the food industries. This review shows that there is increasing evidence to demonstrate that stress can have a significant deleterious effect on food safety through a variety of potential mechanisms. However, as the impact of stress is difficult to precisely determine, it is imperative that the issue receives more research attention in the interests of optimizing animal welfare and minimizing losses in product yield and quality, as well as to food safety risks to consumers. While there is some evidence linking stress with pathogen carriage and shedding in farm animals, the mechanisms underlying this effect have not been fully elucidated. Understanding when pathogen loads on the farm are the highest or when animals are most susceptible to infection will help identifying times when intervention strategies for pathogen control may be most effective, and consequently, increase the safety of food of animal origin.

9 CFR 390.5 - Request for records.

Code of Federal Regulations, 2010 CFR

2010-01-01

....5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION... Coordinator (FOIA Request), Food Safety and Inspection Service, Department of Agriculture, Washington, DC...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

A Historical View and Vision into the Future of the Field of Safety Pharmacology.

PubMed

Bass, Alan S; Hombo, Toshiyasu; Kasai, Chieko; Kinter, Lewis B; Valentin, Jean-Pierre

2015-01-01

Professor Gerhard Zbinden recognized in the 1970s that the standards of the day for testing new candidate drugs in preclinical toxicity studies failed to identify acute pharmacodynamic adverse events that had the potential to harm participants in clinical trials. From his vision emerged the field of safety pharmacology, formally defined in the International Conference on Harmonization (ICH) S7A guidelines as "those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above." Initially, evaluations of small-molecule pharmacodynamic safety utilized efficacy models and were an ancillary responsibility of discovery scientists. However, over time, the relationship of these studies to overall safety was reflected by the regulatory agencies who, in directing the practice of safety pharmacology through guidance documents, prompted transition of responsibility to drug safety departments (e.g., toxicology). Events that have further shaped the field over the past 15 years include the ICH S7B guidance, evolution of molecular technologies leading to identification of new therapeutic targets with uncertain toxicities, introduction of data collection using more sophisticated and refined technologies, and utilization of transgenic animal models probing critical scientific questions regarding novel targets of toxicity. The collapse of the worldwide economy in the latter half of the first decade of the twenty-first century, continuing high rates of compound attrition during clinical development and post-approval and sharply increasing costs of drug development have led to significant strategy changes, contraction of the size of pharmaceutical organizations, and refocusing of therapeutic areas of investigation. With these changes has come movement away from dedicated internal safety pharmacology capability to utilization of capabilities within external contract research organizations. This movement has created the opportunity for the safety pharmacology discipline to come "full circle" and return to the drug discovery arena (target identification through clinical candidate selection) to contribute to the mitigation of the high rate of candidate drug failure through better compound selection decision making. Finally, the changing focus of science and losses in didactic training of scientists in whole animal physiology and pharmacology have revealed a serious gap in the future availability of qualified individuals to apply the principles of safety pharmacology in support of drug discovery and development. This is a significant deficiency that at present is only partially met with academic and professional society programs advancing a minimal level of training. In summary, with the exception that the future availability of suitably trained scientists is a critical need for the field that remains to be effectively addressed, the prospects for the future of safety pharmacology are hopeful and promising, and challenging for those individuals who want to assume this responsibility. What began in the early part of the new millennium as a relatively simple model of testing to assure the safety of Phase I clinical subjects and patients from acute deleterious effects on life-supporting organ systems has grown with experience and time to a science that mobilizes the principles of cellular and molecular biology and attempts to predict acute adverse events and those associated with long-term treatment. These challenges call for scientists with a broad range of in-depth scientific knowledge and an ability to adapt to a dynamic and forever changing industry. Identifying individuals who will serve today and training those who will serve in the future will fall to all of us who are committed to this important field of science.

9 CFR 417.2 - Hazard Analysis and HACCP Plan.

Code of Federal Regulations, 2012 CFR

2012-01-01

... more food safety hazards that are reasonably likely to occur, based on the hazard analysis conducted in... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Hazard Analysis and HACCP Plan. 417.2 Section 417.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

9 CFR 417.2 - Hazard Analysis and HACCP Plan.

Code of Federal Regulations, 2014 CFR

2014-01-01

... more food safety hazards that are reasonably likely to occur, based on the hazard analysis conducted in... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Hazard Analysis and HACCP Plan. 417.2 Section 417.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

9 CFR 417.2 - Hazard Analysis and HACCP Plan.

Code of Federal Regulations, 2011 CFR

2011-01-01

... more food safety hazards that are reasonably likely to occur, based on the hazard analysis conducted in... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Hazard Analysis and HACCP Plan. 417.2 Section 417.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

9 CFR 417.2 - Hazard Analysis and HACCP Plan.

Code of Federal Regulations, 2013 CFR

2013-01-01

... more food safety hazards that are reasonably likely to occur, based on the hazard analysis conducted in... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Hazard Analysis and HACCP Plan. 417.2 Section 417.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

9 CFR 417.2 - Hazard Analysis and HACCP Plan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... more food safety hazards that are reasonably likely to occur, based on the hazard analysis conducted in... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Hazard Analysis and HACCP Plan. 417.2 Section 417.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

9 CFR 392.2 - Definition of petition.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Definition of petition. 392.2 Section 392.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.2 Definition of petition. For purposes of this part, a ...

9 CFR 390.7 - Appeals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Appeals. 390.7 Section 390.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.7 Appeals. (a) If the request for information or for a...

9 CFR 391.3 - Overtime and holiday rates.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Overtime and holiday rates. 391.3 Section 391.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.3 Overtime...

9 CFR 390.5 - Request for records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Request for records. 390.5 Section 390.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.5 Request for records. (a) The FOIA...

9 CFR 390.4 - Facilities for inspection and copying.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Facilities for inspection and copying. 390.4 Section 390.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.4 Facilities for...

9 CFR 392.1 - Scope and purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Scope and purpose. 392.1 Section 392.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.1 Scope and purpose. This part contains provisions governing the...

9 CFR 392.8 - Expedited review.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Expedited review. 392.8 Section 392.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.8 Expedited review. (a) A petition will receive expedited review by...

9 CFR 392.5 - Filing procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Filing procedures. 392.5 Section 392.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.5 Filing procedures. (a) Any interested person may file a petition...

9 CFR 390.8 - Agency response to requests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Agency response to requests. 390.8 Section 390.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.8 Agency response to requests. (a)...

9 CFR 392.8 - Expedited review.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Expedited review. 392.8 Section 392.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.8 Expedited review. (a) A petition will receive expedited review by...

9 CFR 391.1 - Scope and purpose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Scope and purpose. 391.1 Section 391.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.1 Scope and purpose....

9 CFR 392.3 - Required information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Required information. 392.3 Section 392.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.3 Required information. To be considered by FSIS, a petition...

9 CFR 390.7 - Appeals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Appeals. 390.7 Section 390.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.7 Appeals. (a) If the request for information or for a...

9 CFR 392.2 - Definition of petition.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Definition of petition. 392.2 Section 392.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.2 Definition of petition. For purposes of this part, a ...

9 CFR 390.5 - Request for records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Request for records. 390.5 Section 390.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.5 Request for records. (a) The FOIA...

9 CFR 391.3 - Overtime and holiday rates.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Overtime and holiday rates. 391.3 Section 391.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.3 Overtime...

9 CFR 390.6 - Fee schedule.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Fee schedule. 390.6 Section 390.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.6 Fee schedule. Department regulations provide for...

9 CFR 390.6 - Fee schedule.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Fee schedule. 390.6 Section 390.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.6 Fee schedule. Department regulations provide for...

9 CFR 392.6 - Public display.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Public display. 392.6 Section 392.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.6 Public display. (a) All rulemaking petitions filed with FSIS, along...

9 CFR 392.1 - Scope and purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Scope and purpose. 392.1 Section 392.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.1 Scope and purpose. This part contains provisions governing the...

9 CFR 392.8 - Expedited review.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Expedited review. 392.8 Section 392.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.8 Expedited review. (a) A petition will receive expedited review by...

9 CFR 392.6 - Public display.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Public display. 392.6 Section 392.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.6 Public display. (a) All rulemaking petitions filed with FSIS, along...

9 CFR 390.3 - Indexes, reference guide, and handbook.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Indexes, reference guide, and handbook. 390.3 Section 390.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.3 Indexes, reference...

9 CFR 392.7 - Comments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Comments. 392.7 Section 392.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.7 Comments. (a) Any interested person may submit written comments on a...

9 CFR 390.7 - Appeals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Appeals. 390.7 Section 390.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.7 Appeals. (a) If the request for information or for a...

9 CFR 390.1 - Scope and purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Scope and purpose. 390.1 Section 390.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.1 Scope and purpose. This part is issued...

9 CFR 392.5 - Filing procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Filing procedures. 392.5 Section 392.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.5 Filing procedures. (a) Any interested person may file a petition...

9 CFR 390.5 - Request for records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Request for records. 390.5 Section 390.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.5 Request for records. (a) The FOIA...

9 CFR 391.1 - Scope and purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Scope and purpose. 391.1 Section 391.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.1 Scope and purpose....

9 CFR 390.1 - Scope and purpose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Scope and purpose. 390.1 Section 390.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.1 Scope and purpose. This part is issued...

9 CFR 391.2 - Basetime rate.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Basetime rate. 391.2 Section 391.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.2 Basetime rate. (a) For...

9 CFR 391.2 - Basetime rate.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Basetime rate. 391.2 Section 391.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.2 Basetime rate. (a) For...

9 CFR 390.8 - Agency response to requests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Agency response to requests. 390.8 Section 390.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.8 Agency response to requests. (a)...

9 CFR 390.8 - Agency response to requests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Agency response to requests. 390.8 Section 390.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.8 Agency response to requests. (a)...

9 CFR 392.7 - Comments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Comments. 392.7 Section 392.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.7 Comments. (a) Any interested person may submit written comments on a...

9 CFR 390.7 - Appeals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Appeals. 390.7 Section 390.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.7 Appeals. (a) If the request for information or for a...

9 CFR 390.3 - Indexes, reference guide, and handbook.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Indexes, reference guide, and handbook. 390.3 Section 390.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.3 Indexes, reference...

9 CFR 392.7 - Comments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Comments. 392.7 Section 392.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.7 Comments. (a) Any interested person may submit written comments on a...

9 CFR 392.8 - Expedited review.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Expedited review. 392.8 Section 392.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.8 Expedited review. (a) A petition will receive expedited review by...

9 CFR 392.3 - Required information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Required information. 392.3 Section 392.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.3 Required information. To be considered by FSIS, a petition...

9 CFR 390.8 - Agency response to requests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Agency response to requests. 390.8 Section 390.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.8 Agency response to requests. (a)...

9 CFR 390.1 - Scope and purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Scope and purpose. 390.1 Section 390.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.1 Scope and purpose. This part is issued...

9 CFR 392.7 - Comments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Comments. 392.7 Section 392.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.7 Comments. (a) Any interested person may submit written comments on a...

9 CFR 391.4 - Laboratory services rate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Laboratory services rate. 391.4 Section 391.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.4 Laboratory...

9 CFR 391.3 - Overtime and holiday rates.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Overtime and holiday rates. 391.3 Section 391.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.3 Overtime...

9 CFR 391.1 - Scope and purpose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Scope and purpose. 391.1 Section 391.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.1 Scope and purpose....

9 CFR 392.1 - Scope and purpose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Scope and purpose. 392.1 Section 392.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.1 Scope and purpose. This part contains provisions governing the...

9 CFR 391.3 - Overtime and holiday rate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Overtime and holiday rate. 391.3 Section 391.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.3 Overtime an...

9 CFR 392.5 - Filing procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Filing procedures. 392.5 Section 392.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.5 Filing procedures. (a) Any interested person may file a petition...

9 CFR 390.4 - Facilities for inspection and copying.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Facilities for inspection and copying. 390.4 Section 390.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.4 Facilities for...

9 CFR 392.5 - Filing procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Filing procedures. 392.5 Section 392.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.5 Filing procedures. (a) Any interested person may file a petition...

9 CFR 390.4 - Facilities for inspection and copying.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Facilities for inspection and copying. 390.4 Section 390.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.4 Facilities for...

9 CFR 390.6 - Fee schedule.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Fee schedule. 390.6 Section 390.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.6 Fee schedule. Department regulations provide for...

9 CFR 392.2 - Definition of petition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Definition of petition. 392.2 Section 392.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.2 Definition of petition. For purposes of this part, a ...

9 CFR 392.6 - Public display.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Public display. 392.6 Section 392.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.6 Public display. (a) All rulemaking petitions filed with FSIS, along...

9 CFR 390.3 - Indexes, reference guide, and handbook.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Indexes, reference guide, and handbook. 390.3 Section 390.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.3 Indexes, reference...

9 CFR 390.4 - Facilities for inspection and copying.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Facilities for inspection and copying. 390.4 Section 390.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.4 Facilities for...

9 CFR 390.5 - Request for records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Request for records. 390.5 Section 390.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.5 Request for records. (a) The FOIA...

9 CFR 392.2 - Definition of petition.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Definition of petition. 392.2 Section 392.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.2 Definition of petition. For purposes of this part, a ...

9 CFR 390.1 - Scope and purpose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Scope and purpose. 390.1 Section 390.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.1 Scope and purpose. This part is issued...

9 CFR 390.6 - Fee schedule.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Fee schedule. 390.6 Section 390.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.6 Fee schedule. Department regulations provide for...

9 CFR 392.3 - Required information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Required information. 392.3 Section 392.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.3 Required information. To be considered by FSIS, a petition...

9 CFR 391.2 - Basetime rate.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Basetime rate. 391.2 Section 391.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.2 Basetime rate. (a) For...

9 CFR 391.1 - Scope and purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Scope and purpose. 391.1 Section 391.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FEES AND CHARGES FOR INSPECTION SERVICES AND LABORATORY ACCREDITATION § 391.1 Scope and purpose....

9 CFR 392.1 - Scope and purpose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Scope and purpose. 392.1 Section 392.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.1 Scope and purpose. This part contains provisions governing the...

9 CFR 392.3 - Required information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Required information. 392.3 Section 392.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.3 Required information. To be considered by FSIS, a petition...

9 CFR 392.6 - Public display.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Public display. 392.6 Section 392.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.6 Public display. (a) All rulemaking petitions filed with FSIS, along...

9 CFR 390.3 - Indexes, reference guide, and handbook.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Indexes, reference guide, and handbook. 390.3 Section 390.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION § 390.3 Indexes, reference...

Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

PubMed Central

Curtin, François; Perron, Hervé; Kromminga, Arno; Porchet, Hervé; Lang, Alois B

2015-01-01

Monoclonal antibodies (mAbs) play an increasing important role in the therapeutic armamentarium against multiple sclerosis (MS), an inflammatory and degenerative disorder of the central nervous system. Most of the mAbs currently developed for MS are immunomodulators blocking the inflammatory immune process. In contrast with mAbs targeting immune function, GNbAC1, a humanized IgG4 mAb, targets the multiple sclerosis associated retrovirus envelope (MSRV-Env) protein, an upstream factor in the pathophysiology of MS. MSRV-Env protein is of endogenous retroviral origin, expressed in MS brain lesions, and it is pro-inflammatory and toxic to the remyelination process, by preventing the differentiation of oligodendrocyte precursor cells. We present the preclinical and early clinical development results of GNbAC1. The specificity of GNbAC1 for its endogenous retroviral target is described. Efficacy of different mAb versions of GNbAC1 were assessed in MSRV-Env induced experimental allergic encephalitis (EAE), an animal model of MS. Because the target MSRV-Env is not expressed in animals, no relevant animal model exists for a proper in vivo toxicological program. An off-target 2-week toxicity study in mice was thus performed, and it showed an absence of safety risk. Additional in vitro analyses showed an absence of complement or antibody-dependent cytotoxicity as well as a low level of cross-reactivity to human tissues. The first-in-man clinical study in 33 healthy subjects and a long-term clinical study in 10 MS patients showed that GNbAC1 is well tolerated in humans without induction of immunogenicity and that it induces a pharmacodynamic response on MSRV biomarkers. These initial results suggest that the mAb GNbAC1 could be a safe long-term treatment for patients with MS with a unique therapeutic mechanism of action. PMID:25427053

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 391.2 - Base time rate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Base time rate. 391.2 Section 391.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... ACCREDITATION § 391.2 Base time rate. The base time rate for inspection services provided pursuant to §§ 350.7...

9 CFR 390.9 - Communications with State and other Federal government agencies.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Communications with State and other Federal government agencies. 390.9 Section 390.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION §...

9 CFR 390.9 - Communications with State and other Federal government agencies.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Communications with State and other Federal government agencies. 390.9 Section 390.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION §...

9 CFR 390.9 - Communications with State and other Federal government agencies.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Communications with State and other Federal government agencies. 390.9 Section 390.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION §...

9 CFR 390.9 - Communications with State and other Federal government agencies.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Communications with State and other Federal government agencies. 390.9 Section 390.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC INFORMATION §...

9 CFR 391.2 - Base time rate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Base time rate. 391.2 Section 391.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND... ACCREDITATION § 391.2 Base time rate. The base time rate for inspection services provided pursuant to §§ 350.7...

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy.

PubMed

Zarogoulidis, P; Hohenforst-Schmidt, W; Darwiche, K; Krauss, L; Sparopoulou, D; Sakkas, L; Gschwendtner, A; Huang, H; Turner, F J; Freitag, L; Zarogoulidis, K

2013-10-01

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

The role of the pharmaceutical animal health industry in post-marketing surveillance of resistance.

PubMed

Lens, S

1993-06-01

The pharmaceutical animal health industry must be committed to the total life cycle of products, i.e. during both the pre- and post-marketing period. Support of antibacterial agents during the postmarketing period is not restricted to maintaining a well-established distribution and promotion system. Care has to be taken continuously to maintain and/or improve the quality, safety (for user, target animal and environment) and clinical efficacy. The pharmaceutical industry contributes to this by: 1. Introducing antibacterials in different animal species for the most effective disease condition only and by ensuring the veterinary profession is informed about relevant findings on: a. the mechanism of action; b. pharmacodynamic properties; c. pharmacokinetic properties (plasma, target tissue); d. clinical efficacy data and in vitro sensitivity data; e. valid species-specific MIC breakpoints; f. precise dose and treatment regime. 2. Updating on a regular basis on: a. new findings on the mechanism of action (in vitro and in vivo); b. the optimal use program in the light of changes in animal husbandry, farm management and epidemiology on national and international level; c. adjustment of species-specific MIC breakpoints when necessary. 3. Providing continuous information in collaboration with animal health laboratories about: a. clinical field surveillance for efficacy (national, international); b. in vitro sensitivity/resistance surveillance (national, international); c. use of in vitro data to support prediction of in vivo efficacy. Surveillance of resistance, in vitro, is therefore part of a package of information needed on a routine basis by the pharmaceutical industry to allow the best possible use of antibacterials and to minimize induction of resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Multispectral laser-induced fluorescence imaging system for large biological samples

NASA Astrophysics Data System (ADS)

Kim, Moon S.; Lefcourt, Alan M.; Chen, Yud-Ren

2003-07-01

A laser-induced fluorescence imaging system developed to capture multispectral fluorescence emission images simultaneously from a relatively large target object is described. With an expanded, 355-nm Nd:YAG laser as the excitation source, the system captures fluorescence emission images in the blue, green, red, and far-red regions of the spectrum centered at 450, 550, 678, and 730 nm, respectively, from a 30-cm-diameter target area in ambient light. Images of apples and of pork meat artificially contaminated with diluted animal feces have demonstrated the versatility of fluorescence imaging techniques for potential applications in food safety inspection. Regions of contamination, including sites that were not readily visible to the human eye, could easily be identified from the images.

Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

PubMed

Van Voorhis, Wesley C; Doggett, J Stone; Parsons, Marilyn; Hulverson, Matthew A; Choi, Ryan; Arnold, Samuel L M; Riggs, Michael W; Hemphill, Andrew; Howe, Daniel K; Mealey, Robert H; Lau, Audrey O T; Merritt, Ethan A; Maly, Dustin J; Fan, Erkang; Ojo, Kayode K

2017-09-01

Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

9 CFR 300.2 - FSIS responsibilities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 300.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Secretary of Agriculture and Under Secretary for Food Safety have delegated to the Administrator of the Food Safety and Inspection Service the responsibility for exercising the functions of the Secretary of...

9 CFR 390.4 - Facilities for inspection and copying.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 390.4 Section 390.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND PUBLIC... Coordinator (FOIA), Food Safety and Inspection Service, Department of Agriculture, Washington, DC 20250-3700 ...

9 CFR 300.2 - FSIS responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 300.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Secretary of Agriculture and Under Secretary for Food Safety have delegated to the Administrator of the Food Safety and Inspection Service the responsibility for exercising the functions of the Secretary of...

9 CFR 317.5 - Generically approved labeling.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 317.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE..., without such labeling being submitted for approval to the Food Safety and Inspection Service in Washington... particular. (2) The Food Safety and Inspection Service shall select samples of generically approved labeling...

Drug development: from concept to marketing!

PubMed

Tamimi, Nihad A M; Ellis, Peter

2009-01-01

Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.

Determination of sulfonamides in animal tissues by modified QuEChERS and liquid chromatography tandem mass spectrometry.

PubMed

Wen, Ching-Hsuan; Lin, Shu-Ling; Fuh, Ming-Ren

2017-03-01

In this study, the salting-out solvent extraction and dispersive solid-phase extraction (dSPE) clean-up steps in QuEChERS (quick, easy, cheap, effective, rugged, and safe) method were optimized to reduce matrix effect and efficiently extract target sulfonamides from a variety of edible animal tissues. The extracted sulfonamides were then analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Good extraction recoveries (74.0-100.3% in five different sources of animal tissues; n=3) with acceptable matrix effect (<10%, except for liver samples) were obtained using the proposed method. For the first time, a commercial ND-lipids cartridge was used to remove hydrophobic matrix components from fat-rich animal tissues in the clean-up step of QuEChERS. In addition, good linearity (0.125-12.5ngg -1 ) was observed using matrix-matched calibration (in beef). Limits of detection (LODs) were estimated at 0.01-0.03ngg -1 in beef, pork, and chicken samples. For beef tripe and pig liver samples, the LODs were in the range of 0.02-0.04ngg -1 . Good intra-day/inter-day precision (1.0-10.5%/0.4-8.0%) and accuracy (95.2-107.2%/97.8-102.1%) were also achieved using the modified QuEChERS for sample pretreatment. The applicability of the modified QuEChERS-LC-MS/MS method was demonstrated by determining the occurrence of target sulfonamides in various edible animal tissues for potential food safety analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Pathway Based Toxicology and Fit-for-Purpose Assays.

PubMed

Clewell, Rebecca A; McMullen, Patrick D; Adeleye, Yeyejide; Carmichael, Paul L; Andersen, Melvin E

The field of toxicity testing for non-pharmaceutical chemicals is in flux with multiple initiatives in North America and the EU to move away from animal testing to mode-of-action based in vitro assays. In this arena, there are still obstacles to overcome, such as developing appropriate cellular assays, creating pathway-based dose-response models and refining in vitro-in vivo extrapolation (IVIVE) tools. Overall, it is necessary to provide assurances that these new approaches are adequately protective of human and ecological health. Another major challenge for individual scientists and regulatory agencies is developing a cultural willingness to shed old biases developed around animal tests and become more comfortable with mode-of-action based assays in human cells. At present, most initiatives focus on developing in vitro alternatives and assessing how well these alternative methods reproduce past results related to predicting organism level toxicity in intact animals. The path forward requires looking beyond benchmarking against high dose animal studies. We need to develop targeted cellular assays, new cell biology-based extrapolation models for assessing regions of safety for chemical exposures in human populations, and mode-of-action-based approaches which are constructed on an understanding of human biology. Furthermore, it is essential that assay developers have the flexibility to 'validate' against the most appropriate mode-of-action data rather than against apical endpoints in high dose animal studies. This chapter demonstrates the principles of fit-for-purpose assay development using pathway-targeted case studies. The projects include p53-mdm2-mediated DNA-repair, estrogen receptor-mediated cell proliferation and PPARα receptor-mediated liver responses.

Food additives: an ethical evaluation.

PubMed

Mepham, Ben

2011-01-01

Food additives are an integral part of the modern food system, but opinion polls showing most Europeans have worries about them imply an urgent need for ethical analysis of their use. The existing literature on food ethics, safety assessment and animal testing. Food additives provide certain advantages in terms of many people's lifestyles. There are disagreements about the appropriate application of the precautionary principle and of the value and ethical validity of animal tests in assessing human safety. Most consumers have a poor understanding of the relative benefits and risks of additives, but concerns over food safety and animal testing remain high. Examining the impacts of food additives on consumer sovereignty, consumer health and on animals used in safety testing should allow a more informed debate about their appropriate uses.

Estimating the Public Health Impact of Setting Targets at the European Level for the Reduction of Zoonotic Salmonella in Certain Poultry Populations

PubMed Central

Messens, Winy; Vivas-Alegre, Luis; Bashir, Saghir; Amore, Giusi; Romero-Barrios, Pablo; Hugas, Marta

2013-01-01

In the European Union (EU), targets are being set for the reduction of certain zoonotic Salmonella serovars in different animal populations, including poultry populations, within the framework of Regulation (EC) No. 2160/2003 on the control of zoonoses. For a three-year transitional period, the EU targets were to cover only Salmonella Enteritidis and S. Typhimurium (and in addition S. Hadar, S. Infantis and S. Virchow for breeding flocks of Gallus gallus). Before the end of that transitional period, the revision of the EU targets was to be considered, including the potentially addition of other serovars with public health significance to the permanent EU targets. This review article aims at providing an overview of the assessments carried out by the Scientific Panel on Biological Hazards of the European Food Safety Authority in the field of setting targets for Salmonella in poultry populations (breeding flocks of Gallus gallus, laying flocks of Gallus gallus, broiler flocks of Gallus gallus and flocks of breeding and fattening turkeys) and their impact in subsequent changes in EU legislation. PMID:24157508

9 CFR 390.10 - Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls. 390.10 Section 390.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND...

9 CFR 390.10 - Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls. 390.10 Section 390.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND...

9 CFR 390.10 - Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls. 390.10 Section 390.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND...

9 CFR 390.10 - Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Availability of Lists of Retail Consignees during Meat or Poultry Product Recalls. 390.10 Section 390.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF INFORMATION AND...

Deep Sequencing of Plant and Animal DNA Contained within Traditional Chinese Medicines Reveals Legality Issues and Health Safety Concerns

PubMed Central

Coghlan, Megan L.; Haile, James; Houston, Jayne; Murray, Dáithí C.; White, Nicole E.; Moolhuijzen, Paula; Bellgard, Matthew I.; Bunce, Michael

2012-01-01

Traditional Chinese medicine (TCM) has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES) legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS) of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus) and Saiga antelope (Saiga tatarica). Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety especially when plant reference databases become better established. PMID:22511890

9 CFR 317.5 - Generically approved labeling.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 317.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... the Food Safety and Inspection Service in Washington or the field, provided the labeling is in..., and is not otherwise false or misleading in any particular. (2) The Food Safety and Inspection Service...

9 CFR 317.5 - Generically approved labeling.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 317.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... the Food Safety and Inspection Service in Washington or the field, provided the labeling is in..., and is not otherwise false or misleading in any particular. (2) The Food Safety and Inspection Service...

9 CFR 317.5 - Generically approved labeling.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 317.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... the Food Safety and Inspection Service in Washington or the field, provided the labeling is in..., and is not otherwise false or misleading in any particular. (2) The Food Safety and Inspection Service...

9 CFR 317.5 - Generically approved labeling.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 317.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... the Food Safety and Inspection Service in Washington or the field, provided the labeling is in..., and is not otherwise false or misleading in any particular. (2) The Food Safety and Inspection Service...

Cardiac AAV9-S100A1 gene therapy rescues postischemic heart failure in a preclinical large animal model

PubMed Central

Pleger, Sven T.; Shan, Changguang; Ksienzyk, Jan; Bekeredjian, Raffi; Boekstegers, Peter; Hinkel, Rabea; Schinkel, Stefanie; Leuchs, Barbara; Ludwig, Jochen; Qiu, Gang; Weber, Christophe; Kleinschmidt, Jürgen A.; Raake, Philip; Koch, Walter J.; Katus, Hugo A.; Müller, Oliver J.; Most, Patrick

2014-01-01

As a prerequisite to clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated viral (AAV) S100A1 gene therapy in a preclinical, large animal model of heart failure. S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and various animal models, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium Ca2+ handling in acutely and chronically failing hearts in small animal models. We induced heart failure in domestic pigs by balloon-occlusion of the left circumflex coronary artery, resulting in myocardial infarction. After 2 weeks, when the pigs displayed significant left ventricular contractile dysfunction, we administered through retrograde coronary venous delivery, AAV9-S100A1 to the left ventricular non-infarcted myocardium. AAV9-luciferase and saline treatment served as control. At 14 weeks, both control groups showed significantly decreased myocardial S100A1 protein expression along with progressive deterioration of cardiac performance and left ventricular remodeling. AAV9-S100A1 treatment prevented and reversed this phenotype by restoring cardiac S100A1 protein levels. S100A1 treatment normalized cardiomyocyte Ca2+ cycling, sarcoplasmic reticulum calcium handling and energy homeostasis. Transgene expression was restricted to cardiac tissue and extra-cardiac organ function was uncompromised indicating a favorable safety profile. This translational study shows the pre-clinical feasibility, long-term therapeutic effectiveness and a favorable safety profile of cardiac AAV9-S100A1 gene therapy in a preclinical model of heart failure. Our study presents a strong rational for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure. PMID:21775667

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

Catalytic Properties and Biomedical Applications of Cerium Oxide Nanoparticles

PubMed Central

Walkey, Carl; Das, Soumen; Seal, Sudipta; Erlichman, Joseph; Heckman, Karin; Ghibelli, Lina; Traversa, Enrico; McGinnis, James F.; Self, William T.

2014-01-01

Cerium oxide nanoparticles (Nanoceria) have shown promise as catalytic antioxidants in the test tube, cell culture models and animal models of disease. However given the reactivity that is well established at the surface of these nanoparticles, the biological utilization of Nanoceria as a therapeutic still poses many challenges. Moreover the form that these particles take in a biological environment, such as the changes that can occur due to a protein corona, are not well established. This review aims to summarize the existing literature on biological use of Nanoceria, and to raise questions about what further study is needed to apply this interesting catalytic material to biomedical applications. These questions include: 1) How does preparation, exposure dose, route and experimental model influence the reported effects of Nanoceria in animal studies? 2) What are the considerations to develop Nanoceria as a therapeutic agent in regards to these parameters? 3) What biological targets of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are relevant to this targeting, and how do these properties also influence the safety of these nanomaterials? PMID:26207185

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

PubMed

Balls, Michael; Clothier, Richard

2010-10-01

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

Modern science for better quality control of medicinal products "Towards global harmonization of 3Rs in biologicals": The report of an EPAA workshop.

PubMed

Schutte, Katrin; Szczepanska, Anna; Halder, Marlies; Cussler, Klaus; Sauer, Ursula G; Stirling, Catrina; Uhlrich, Sylvie; Wilk-Zasadna, Iwona; John, David; Bopst, Martin; Garbe, Joerg; Glansbeek, Harrie L; Levis, Robin; Serreyn, Pieter-Jan; Smith, Dean; Stickings, Paul

2017-07-01

This article summarizes the outcome of an international workshop organized by the European Partnership for Alternative Approaches to Animal Testing (EPAA) on Modern science for better quality control of medicinal products: Towards global harmonization of 3Rs in biologicals. As regards the safety testing of biologicals, the workshop participants agreed to actively encourage the deletion of abnormal toxicity tests and target animal batch safety tests from all relevant legal requirements and guidance documents (country-specific guidelines, pharmacopoeia monographs, WHO recommendations). To facilitate the global regulatory acceptance of non-animal methods for the potency testing of, e.g., human diphtheria and tetanus vaccines and veterinary swine erysipelas vaccines, international convergence on the scientific principles of the use of appropriately validated in vitro assays for replacing in vivo methods was identified as an overarching goal. The establishment of scientific requirements for new assays was recognized as a further means to unify regulatory approaches in different jurisdictions. It was recommended to include key regulators and manufacturers early in the corresponding discussions. Manufacturers and responsible expert groups, e.g. at the European Directorate for the Quality of Medicines and Health Care of the Council of Europe or the European Medicines Agency, were invited to consider leadership for international collaboration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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.

A Potent Oncolytic Herpes Simplex Virus for Therapy of Advanced Prostate Cancer

DTIC Science & Technology

2005-07-01

DNA replication in the targeted cells. As oncolytic HSV can only initiate - viral replication in tumor cells, this restricts the syncytial formation from virus infection to malignant cells only. Therefore fusogenic oncolytic HSV should be no more toxic than its parental construct. Nonetheless, we proposed in the year 2 of this funded project to conduct extensive studies in animal models to confirm its safety in vivo. The results obtained so far from these experiments have demonstrated that the fusogenic oncolytic HSV is indeed not significantly more toxic than the

Safety Precautions for Science.

ERIC Educational Resources Information Center

Folks, John; And Others

Safety information is discussed and outlined in this guide. Areas include: (1) general laboratory safety rules; (2) general rules and guidelines for animals in the elementary classroom; (3) general guidelines for the physical sciences; (4) general rules for using animals in investigations, with specifics on the care and handling of mammals,…

Assessing Student Attitudes toward Animal Welfare, Resource Use, and Food Safety.

ERIC Educational Resources Information Center

Nordstrom, Patricia A.; Richards, Martha J.; Wilson, Lowell L.; Coe, Brenda L.; Fivek, Marianne L.; Brown, Michele B.

2000-01-01

Students participating in the Pennsylvania Governor's School for Agricultural Sciences (n=192) studied animal welfare, resource use, and food safety. They ranked food safety as a primary concern. Students with and without agricultural backgrounds showed positive changes in knowledge and perception of issues after the course. (SK)

9 CFR 390.9 - Communications with State and other Federal government agencies.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Federal government agencies. 390.9 Section 390.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS FREEDOM OF...) The Administrator of the Food Safety and Inspection Service (FSIS), or designee, may authorize the...

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach

PubMed Central

Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

2017-01-01

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. PMID:28494844

21 CFR 522.2477 - Trenbolone acetate and estradiol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... subcutaneously in ear only. Do not use in animals intended for subsequent breeding or in dairy animals. Safety... intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been established in... not use in calves to be processed for veal. (3) Pasture cattle (slaughter, stocker, and feeder steers...

21 CFR 522.2477 - Trenbolone acetate and estradiol.

Code of Federal Regulations, 2012 CFR

2012-04-01

... subcutaneously in ear only. Do not use in animals intended for subsequent breeding or in dairy animals. Safety... intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been established in... not use in calves to be processed for veal. (3) Pasture cattle (slaughter, stocker, and feeder steers...

21 CFR 522.2477 - Trenbolone acetate and estradiol.

Code of Federal Regulations, 2013 CFR

2013-04-01

... subcutaneously in ear only. Do not use in animals intended for subsequent breeding or in dairy animals. Safety... intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been established in... not use in calves to be processed for veal. (3) Pasture cattle (slaughter, stocker, and feeder steers...

21 CFR 522.2477 - Trenbolone acetate and estradiol.

Code of Federal Regulations, 2011 CFR

2011-04-01

... subcutaneously in ear only. Do not use in animals intended for subsequent breeding or in dairy animals. Safety... intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been established in... not use in calves to be processed for veal. (3) Pasture cattle (slaughter, stocker, and feeder steers...

21 CFR 522.2477 - Trenbolone acetate and estradiol.

Code of Federal Regulations, 2014 CFR

2014-04-01

... subcutaneously in ear only. Do not use in animals intended for subsequent breeding or in dairy animals. Safety... intended for subsequent breeding or in dairy animals. Safety and effectiveness have not been established in... not use in calves to be processed for veal. (3) Pasture cattle (slaughter, stocker, and feeder steers...

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

PubMed

Li, Nan; Weng, Dong; Wang, Shan-Mei; Zhang, Yuan; Chen, Shan-Shan; Yin, Zhao-Fang; Zhai, Jiali; Scoble, Judy; Williams, Charlotte C; Chen, Tao; Qiu, Hui; Wu, Qin; Zhao, Meng-Meng; Lu, Li-Qin; Mulet, Xavier; Li, Hui-Ping

2017-11-01

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

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

Amacher, David E.

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intendedmore » human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other 'omics' technologies can provide added selectivity and sensitivity in preclinical drug safety testing.« less

Nanotech: propensity in foods and bioactives.

PubMed

Kuan, Chiu-Yin; Yee-Fung, Wai; Yuen, Kah-Hay; Liong, Min-Tze

2012-01-01

Nanotechnology is seeing higher propensity in various industries, including food and bioactives. New nanomaterials are constantly being developed from both natural biodegradable polymers of plant and animal origins such as polysaccharides and derivatives, peptides and proteins, lipids and fats, and biocompatible synthetic biopolyester polymers such as polylactic acid (PLA), polyhydroxyalkonoates (PHA), and polycaprolactone (PCL). Applications in food industries include molecular synthesis of new functional food compounds, innovative food packaging, food safety, and security monitoring. The relevance of bioactives includes targeted delivery systems with improved bioavailability using nanostructure vehicles such as association colloids, lipid based nanoencapsulator, nanoemulsions, biopolymeric nanoparticles, nanolaminates, and nanofibers. The extensive use of nanotechnology has led to the need for parallel safety assessment and regulations to protect public health and adverse effects to the environment. This review covers the use of biopolymers in the production of nanomaterials and the propensity of nanotechnology in food and bioactives. The exposure routes of nanoparticles, safety challenges, and measures undertaken to ensure optimal benefits that outweigh detriments are also discussed.

Biosonar behaviour of free-ranging porpoises.

PubMed

Akamatsu, Tomonari; Wang, Ding; Wang, Kexiong; Naito, Yasuhiko

2005-04-22

Detecting objects in their paths is a fundamental perceptional function of moving organisms. Potential risks and rewards, such as prey, predators, conspecifics or non-biological obstacles, must be detected so that an animal can modify its behaviour accordingly. However, to date few studies have considered how animals in the wild focus their attention. Dolphins and porpoises are known to actively use sonar or echolocation. A newly developed miniature data logger attached to a porpoise allows for individual recording of acoustical search efforts and inspection distance based on echolocation. In this study, we analysed the biosonar behaviour of eight free-ranging finless porpoises (Neophocaena phocaenoides) and demonstrated that these animals inspect the area ahead of them before swimming silently into it. The porpoises inspected distances up to 77 m, whereas their swimming distance without using sonar was less than 20 m. The inspection distance was long enough to ensure a wide safety margin before facing real risks or rewards. Once a potential prey item was detected, porpoises adjusted their inspection distance from the remote target throughout their approach.

Retinoid-related orphan receptor γ (RORγ) adult induced knockout mice develop lymphoblastic lymphoma.

PubMed

Liljevald, Maria; Rehnberg, Maria; Söderberg, Magnus; Ramnegård, Marie; Börjesson, Jenny; Luciani, Donatella; Krutrök, Nina; Brändén, Lena; Johansson, Camilla; Xu, Xiufeng; Bjursell, Mikael; Sjögren, Anna-Karin; Hornberg, Jorrit; Andersson, Ulf; Keeling, David; Jirholt, Johan

2016-11-01

RORγ is a nuclear hormone receptor which controls polarization of naive CD4 + T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORγ has therapeutic potential for autoimmune diseases; however, this mechanism may potentially carry target-related safety risks, as mice deficient in Rorc, the gene encoding RORγ, develop T-cell lymphoma with 50% frequency. Due to the requirement of RORγ during development, the Rorc knockout (KO) animals lack secondary lymphoid organs and have a dysregulation in the generation of CD4+ and CD8+ T cells. We wanted to extend the evaluation of RORγ deficiency to address the question whether lymphomas, similar to those observed in the Rorc KO, would develop in an animal with an otherwise intact adult immune system. Accordingly, we designed a conditional RORγ knockout mouse (Rorc CKO) where the Rorc locus could be deleted in adult animals. Based on these studies we can confirm that these animals also develop lymphoma in a similar time frame as embryonic Rorc knockouts. This study also suggests that in animals where the gene deletion is incomplete, the thymus undergoes a rapid selection process replacing Rorc deficient cells with remnant thymocytes carrying a functional Rorc locus and that subsequently, these animals do not develop lymphoblastic lymphoma. Copyright © 2016 Elsevier B.V. All rights reserved.

76 FR 13638 - Ensuring the Safety of Imported Foods and Animal Feed: Comparability of Food Safety Systems and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Practices of Foreign Countries; Public Hearing; Request for Comments AGENCY: Food and Drug Administration... regulators in other countries regarding the regulatory policies, practices, and programs they currently use to ensure the safety of foods and animal feed imported into their countries. In a separate notice...

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

PubMed

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

2012-06-01

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

Veterinary Safety's Conflicts in the EAEU

ERIC Educational Resources Information Center

Kalymbek, Bakytzhan; Shulanbekova, Gulmira K.; Madiyarova, Ainur S.; Mirambaeva, Gulnaz Zh.

2016-01-01

This article is devoted to the problem of veterinary safety of the countries under the Eurasian Economic Union. Animal health's measures are provided in order to prevent the entry and spread of infectious animal diseases, including common to humans and animals, as well as goods not conforming to the common veterinary and sanitary requirements.…

The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

PubMed

Sze, N N; Wong, S C; Lee, C Y

2014-12-01

In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation of Bioreactor and Human-on-a-Chip Devices for Chemical Safety Assessment.

PubMed

Rebelo, Sofia P; Dehne, Eva-Maria; Brito, Catarina; Horland, Reyk; Alves, Paula M; Marx, Uwe

2016-01-01

Equipment and device qualification and test assay validation in the field of tissue engineered human organs for substance assessment remain formidable tasks with only a few successful examples so far. The hurdles seem to increase with the growing complexity of the biological systems, emulated by the respective models. Controlled single tissue or organ culture in bioreactors improves the organ-specific functions and maintains their phenotypic stability for longer periods of time. The reproducibility attained with bioreactor operations is, per se, an advantage for the validation of safety assessment. Regulatory agencies have gradually altered the validation concept from exhaustive "product" to rigorous and detailed process characterization, valuing reproducibility as a standard for validation. "Human-on-a-chip" technologies applying micro-physiological systems to the in vitro combination of miniaturized human organ equivalents into functional human micro-organisms are nowadays thought to be the most elaborate solution created to date. They target the replacement of the current most complex models-laboratory animals. Therefore, we provide here a road map towards the validation of such "human-on-a-chip" models and qualification of their respective bioreactor and microchip equipment along a path currently used for the respective animal models.

Evaluation of Biodistribution and Safety of Adenovirus Vectors Containing Group B Fibers after Intravenous Injection into Baboons

PubMed Central

NI, SHAOHENG; BERNT, KATHRIN; GAGGAR, ANUJ; LI, ZONG-YI; KIEM, HANS-PETER; LIEBER, ANDRÉ

2005-01-01

Vectors containing group B adenovirus (Ad) fibers are able to efficiently transduce gene therapy targets that are refractory to infection with standard Ad serotype 5 (Ad5) vectors, including malignant tumor cells, hematopoietic stem cells, and dendritic cells. Preliminary studies in mice indicate that, after intravenous injection, B-group fiber-containing Ads do not efficiently transduce most organs and cause less acute toxicity than Ad5 vectors. However, biodistribution and safety studies in mice are of limited value because the mouse analog of the B-group Ad receptor, CD46, is expressed only in the testis, whereas in humans, CD46 is expressed on all nucleated cells. Unlike mice, baboons have CD46 expression patterns and levels that closely mimic those in humans. We conducted a biodistribution and toxicity study of group B Ad fiber-containing vectors in baboons. Animals received phosphate-buffered saline, Ad5-bGal (a first-generation Ad5 vector), or B-group fiber-containing Ads (Ad5/35-bGal and Ad5/11-bGal) at a dose of 2 × 1012 VP/kg, and vector biodistribution and safety was analyzed over 3 days. The amount of Ad5/35-bGal and Ad5/11-bGal vector genomes was in most tissues one to three orders of magnitude below that of Ad5. Significant Ad5/35- and Ad5/11-mediated transgene (β-galactosidase) expression was seen only in the marginal zone of splenic follicles. Compared with the animal that received Ad5-bGal, all animals injected with B-group fiber-containing Ad vectors had lower elevations in serum proinflammatory cytokine levels. Gross and histopathology were normal in animals that received B-group Ad fiber-containing Ads, in contrast to the Ad5-infused animal, which showed widespread endothelial damage and inflammation. In a further study, a chimeric Ad5/35 vector carrying proapoptotic TRAIL and Ad E1A genes under tumor-specific regulation was well tolerated in a 30-day toxicity study. No major clinical, serologic, or pathologic abnormalities were noticed in this animal. OVERVIEW SUMMARY B-group Ad fiber-containing vectors are promising tools for gene therapy, for example, for the treatment of metastatic cancer or cardiovascular diseases, or for vaccination/immunotherapy. However, only a few studies of vectors containing B-group Ad fibers in mice have been conducted so far, and little is known about the mechanisms and effects of B-group Ad vector delivery in vivo. Before these vectors can be considered for clinical application, this knowledge gap must be filled. We performed biodistribution and safety studies after intravenous injection of chimeric Ad5 vectors containing Ad35 and Ad11 fibers into baboons. Our study suggests that Ad vectors possessing B-group Ad fibers have a better safety profile after intravenous injection than do conventional Ad5-based vectors. PMID:15960598

Plant-based vaccines for Alzheimer's disease: an overview.

PubMed

Rosales-Mendoza, Sergio; Rubio-Infante, Néstor; Zarazúa, Sergio; Govea-Alonso, Dania O; Martel-Gallegos, Guadalupe; Moreno-Fierros, Leticia

2014-03-01

Plants are considered advantageous platforms for biomanufacturing recombinant vaccines. This constitutes a field of intensive research and some plant-derived vaccines are expected to be marketed in the near future. In particular, plant-based production of immunogens targeting molecules with implications on the pathology of Alzheimer's has been explored over the last decade. These efforts involve targeting amyloid beta and β-secretase with several immunogen configurations that have been evaluated in test animals. The results of these developments are analyzed in this review. Perspectives on the topic are identified, such as exploring additional antigen configurations and adjuvants in order to improve immunization schemes, characterizing in detail the elicited immune responses, and immunological considerations in the achievement of therapeutic humoral responses via mucosal immunization. Safety concerns related to these therapies will also be discussed.

Liver-Directed Lentiviral Gene Therapy in a Dog Model of Hemophilia B

PubMed Central

Bartholomae, Cynthia C.; Volpin, Monica; Della Valle, Patrizia; Sanvito, Francesca; Sergi Sergi, Lucia; Gallina, Pierangela; Benedicenti, Fabrizio; Bellinger, Dwight; Raymer, Robin; Merricks, Elizabeth; Bellintani, Francesca; Martin, Samia; Doglioni, Claudio; D’Angelo, Armando; VandenDriessche, Thierry; Chuah, Marinee K.; Schmidt, Manfred; Nichols, Timothy; Montini, Eugenio; Naldini, Luigi

2017-01-01

We investigated the safety and efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B, and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We show that gene therapy using lentiviral vectors targeting expression of a canine factor IX transgene to hepatocytes was well-tolerated and provided stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we show that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be useful for the treatment of hemophilia. PMID:25739762

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

PubMed

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.

An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food

PubMed Central

Majdinasab, Marjan; Yaqub, Mustansara; Rahim, Abdur; Catanante, Gaelle; Hayat, Akhtar; Marty, Jean Louis

2017-01-01

Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food. PMID:28837093

Pre-clinical and Clinical Safety Studies of CMX-2043: A Cytoprotective Lipoic Acid Analogue for Ischaemia–Reperfusion Injury

PubMed Central

Kates, Steven A; Lader, Alan S; Casale, Ralph; Beeuwkes, Reinier

2014-01-01

CMX-2043 is an α-lipoic acid analogue targeted to reduction of cellular injury and organ damage due to ischaemia–reperfusion injury (IRI). It has been shown to be effective in a rat model of cardiac IRI. The studies here reported evaluate its safety and pharmacokinetic profile in preparation for human clinical studies in procedures associated with IRI. Safety and tolerability were tested in standard pre-clinical in vitro and animal models and in a Phase 1 human clinical trial. CMX-2043 did not bind to a wide range of receptors and specific targets at approximately 4 μg/mL (10 μM). It was not mutagenic by Ames assay, did not produce chromosome aberrations in Chinese hamster ovary (CHO) cells, and was negative for clastogenic potential. Toxicological studies in rats including both single and 14-day repeat intravenous doses and in dogs (single intravenous dose) with a 2-week recovery period were conducted. The NOAEL in rats and dogs was 30 and >10 mg/kg, respectively. No serious adverse events were reported in a placebo-controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity in the pre-clinical studies and the absence of adverse events in the Phase 1 trial have supported investigation of CMX-2043 in a human efficacy trial. PMID:24751172

Percutaneous irreversible electroporation for breast tissue and breast cancer: safety, feasibility, skin effects and radiologic-pathologic correlation in an animal study.

PubMed

Li, Sheng; Chen, Fei; Shen, Lujun; Zeng, Qi; Wu, Peihong

2016-08-05

To study the safety, feasibility and skin effects of irreversible electroporation (IRE) for breast tissue and breast cancer in animal models. Eight pigs were used in this study. IRE was performed on the left breasts of the pigs with different skin-electrode distances, and the right breasts were used as controls. The electrodes were placed 1-8 mm away from the skin, with an electrode spacing of 1.5-2 cm. Imaging and pathological examinations were performed at specific time points for follow-up evaluation. Vital signs, skin damage, breast tissue changes and ablation efficacy were also closely observed. Eight rabbit models with or without VX2 breast tumor implantations were used to further assess the damage caused by and the repair of thin skin after IRE treatment for breast cancer. Contrast-enhanced ultrasound and elastosonography were used to investigate ablation efficacy and safety. During IRE, the color of the pig breast skin reversibly changed. When the skin-electrode distance was 3 mm, the breast skin clearly changed, becoming white in the center and purple in the surrounding region during IRE. One small purulent skin lesion was detected several days after IRE. When the skin-electrode distance was 5-8 mm, the breast skin became red during IRE. However, the skin architecture was normal when evaluated using gross pathology and hematoxylin-eosin staining. When the skin-electrode distance was 1 mm, skin atrophy and yellow glabrescence occurred in the rabbit breasts after IRE. When the skin-electrode distance was ≥5 mm, there was no skin damage in the rabbit model regardless of breast cancer implantation. After IRE, complete ablation of the targeted breast tissue or cancer was confirmed, and apoptosis was detected in the target tissue and outermost epidermal layer. In the ablated breasts of the surviving animals, complete mammary regeneration with normal skin and hair was observed. Furthermore, no massive fibrosis or mass formation were detected on ultrasound or through hematoxylin-eosin staining. After IRE, the skin architecture was well preserved when the skin-electrode distance was ≥5 mm. Moreover, breast regeneration occurred without mass formation or obvious fibrosis.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequentmore » challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.« less

International trade standards for commodities and products derived from animals: the need for a system that integrates food safety and animal disease risk management.

PubMed

Thomson, G R; Penrith, M-L; Atkinson, M W; Thalwitzer, S; Mancuso, A; Atkinson, S J; Osofsky, S A

2013-12-01

A case is made for greater emphasis to be placed on value chain management as an alternative to geographically based disease risk mitigation for trade in commodities and products derived from animals. The geographic approach is dependent upon achievement of freedom in countries or zones from infectious agents that cause so-called transboundary animal diseases, while value chain-based risk management depends upon mitigation of animal disease hazards potentially associated with specific commodities or products irrespective of the locality of production. This commodity-specific approach is founded on the same principles upon which international food safety standards are based, viz. hazard analysis critical control points (HACCP). Broader acceptance of a value chain approach enables animal disease risk management to be combined with food safety management by the integration of commodity-based trade and HACCP methodologies and thereby facilitates 'farm to fork' quality assurance. The latter is increasingly recognized as indispensable to food safety assurance and is therefore a pre-condition to safe trade. The biological principles upon which HACCP and commodity-based trade are based are essentially identical, potentially simplifying sanitary control in contrast to current separate international sanitary standards for food safety and animal disease risks that are difficult to reconcile. A value chain approach would not only enable more effective integration of food safety and animal disease risk management of foodstuffs derived from animals but would also ameliorate adverse environmental and associated socio-economic consequences of current sanitary standards based on the geographic distribution of animal infections. This is especially the case where vast veterinary cordon fencing systems are relied upon to separate livestock and wildlife as is the case in much of southern Africa. A value chain approach would thus be particularly beneficial to under-developed regions of the world such as southern Africa specifically and sub-Saharan Africa more generally where it would reduce incompatibility between attempts to expand and commercialize livestock production and the need to conserve the subcontinent's unparalleled wildlife and wilderness resources. © 2013 Blackwell Verlag GmbH.

[Food safety and animal diseases. The French Food Safety Agency, from mad cow disease to bird flu].

PubMed

Keck, Frédéric

2008-01-01

Why has the French food safety agency been particularly mobilized on zoonoses like bovine spongiform encephalopathy ("mad cow disease") or highly pathogenic avian influenza ("bird flu") ? Because sanitary crisis make explicit an ambivalent relationship between humans and animals (animals being perceived alternatively as providers of goods and as bearers of threats), and to the circulation of life in general (the contaminated blood crises being due to the rapprochement of blood giving and blood receiving). The sociology of risks needs therefore to reintegrate the idea of an intention of the risk bearer (risk with enemy), and the sociology of alimentation needs to reintegrate the analysis of the conditions of production. Mad cow disease is the paradigmatic food safety crisis because it brings together the poles of production and consumption, of animals and humans. It therefore belongs to anthropology.

Integrating animal health and food safety surveillance data from slaughterhouse control.

PubMed

Lynch, J A; Silva, P

2013-08-01

Surveillance at the slaughterhouse level for animal health and food safety purposes encompasses examination for the presence of pathology, pathogens, drug residues, chemical contaminants and antimicrobial resistance. Government, industry and academia are the primary proponents of such surveillance. A variety of policies and policy instruments from voluntary to legislative may be applied to promote or obligate participation. Efforts to integrate data across such diverse organisations encounter significant legal, logistical and financial challenges. Enhancement of policies to encourage effective integration of animal health and food safety surveillance data from slaughterhouse control should promote: a long-term approach; collaboration among government, industry and academia; application of a risk-based scheme; and transparent public access to data, with generation of consumer-oriented communications derived from the data. A strong case can be made that the complementary pursuit of both sustainable animal health and food safety can continue to be aided by surveillance at the slaughterhouse level.

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

PubMed

Van Eenennaam, Alison L

2013-09-25

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

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

PubMed Central

2013-01-01

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away from a GE evaluation process that currently focuses only on risk assessment and identifying ever diminishing marginal hazards, to a regulatory approach that more objectively evaluates and communicates the likely impact of approving a new GE plant or animal on agricultural production systems. PMID:24066781

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... use. Target tissue means the edible tissue selected to monitor for residues in the target animals...

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... use. Target tissue means the edible tissue selected to monitor for residues in the target animals...

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

PubMed Central

Kim, Seung Won; Kim, Bae-Hwan

2016-01-01

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a 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. PMID:27437094

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

PubMed

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.

Lightning safety of animals.

PubMed

Gomes, Chandima

2012-11-01

This paper addresses a concurrent multidisciplinary problem: animal safety against lightning hazards. In regions where lightning is prevalent, either seasonally or throughout the year, a considerable number of wild, captive and tame animals are injured due to lightning generated effects. The paper discusses all possible injury mechanisms, focusing mainly on animals with commercial value. A large number of cases from several countries have been analyzed. Economically and practically viable engineering solutions are proposed to address the issues related to the lightning threats discussed.

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

PubMed

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

2016-05-25

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders

PubMed Central

Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya

2016-01-01

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

76 FR 76874 - Implementation of Regulations Required Under Title XI of the Food, Conservation and Energy Act of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

..., including those that could improve food safety. Although there were many comments received in favor of this... agreement if the grower failed to comply with the processor's internal food safety or animal welfare... reputations if required to allow a grower to operate following a breach involving food safety or animal...

2 CFR 417.215 - Which nonprocurement transactions, in addition to those listed in 2 CFR 180.215, are not covered...

Code of Federal Regulations, 2013 CFR

2013-01-01

... of Federal timber governed by the Forest Resources Conservation and Shortage Relief Act of 1990, 16 U... interest of public health and safety, and animal and plant health and safety. (4) The receipt of official grading and inspection services, animal damage control services, public health and safety inspection...

2 CFR 417.215 - Which nonprocurement transactions, in addition to those listed in 2 CFR 180.215, are not covered...

Code of Federal Regulations, 2014 CFR

2014-01-01

... of Federal timber governed by the Forest Resources Conservation and Shortage Relief Act of 1990, 16 U... interest of public health and safety, and animal and plant health and safety. (4) The receipt of official grading and inspection services, animal damage control services, public health and safety inspection...

2 CFR 417.215 - Which nonprocurement transactions, in addition to those listed in 2 CFR 180.215, are not covered...

Code of Federal Regulations, 2012 CFR

2012-01-01

... of Federal timber governed by the Forest Resources Conservation and Shortage Relief Act of 1990, 16 U... interest of public health and safety, and animal and plant health and safety. (4) The receipt of official grading and inspection services, animal damage control services, public health and safety inspection...

2 CFR 417.215 - Which nonprocurement transactions, in addition to those listed in 2 CFR 180.215, are not covered...

Code of Federal Regulations, 2011 CFR

2011-01-01

... of Federal timber governed by the Forest Resources Conservation and Shortage Relief Act of 1990, 16 U... interest of public health and safety, and animal and plant health and safety. (4) The receipt of official grading and inspection services, animal damage control services, public health and safety inspection...

Developing a Comprehensive Animal Care Occupational Health and Safety Program at a Land-Grant Institution

PubMed Central

Goodly, Lyndon J; Jarrell, Vickie L; Miller, Monica A; Banks, Maureen C; Anderson, Thomas J; Branson, Katherine A; Woodward, Robert T; Peper, Randall L; Myers, Sara J

2016-01-01

The Public Health Service Policy on the Humane Care and Use of Laboratory Animals and sound ethical practices require institutions to provide safe working environments for personnel working with animals; this mandate is achieved in part by establishing an effective animal care Occupational Health and Safety Program (OHSP). Land-grant institutions often face unique organizational challenges in fulfilling this requirement. For example, responsibilities for providing health and safety programs often have historically been dispersed among many different divisions scattered around the campus. Here we describe how our institutional management personnel overcame organizational structure and cultural obstacles during the formation of a comprehensive campus-wide animal care OHSP. Steps toward establishing the animal care OHSP included assigning overall responsibility, identifying all stakeholders, creating a leadership group, and hiring a fulltime Animal Care OHSP Specialist. A web-based portal was developed, implemented, and refined over the past 7 y and reflected the unique organizational structures of the university and the needs of our research community. Through this web-based portal, hazards are identified, risks are assessed, and training is provided. The animal care OHSP now provides easy mandatory enrollment, supports timely feedback regarding hazards, and affords enrollees the opportunity to participate in voluntary medical surveillance. The future direction and development of the animal care OHSP will be based on the research trends of campus, identification of emerging health and safety hazards, and ongoing evaluation and refinement of the program. PMID:26817980

Developing a Comprehensive Animal Care Occupational Health and Safety Program at a Land-Grant Institution.

PubMed

Goodly, Lyndon J; Jarrell, Vickie L; Miller, Monica A; Banks, Maureen C; Anderson, Thomas J; Branson, Katherine A; Woodward, Robert T; Peper, Randall L; Myers, Sara J

2016-01-01

The Public Health Service Policy on the Humane Care and Use of Laboratory Animals and sound ethical practices require institutions to provide safe working environments for personnel working with animals; this mandate is achieved in part by establishing an effective animal care Occupational Health and Safety Program (OHSP). Land-grant institutions often face unique organizational challenges in fulfilling this requirement. For example, responsibilities for providing health and safety programs often have historically been dispersed among many different divisions scattered around the campus. Here we describe how our institutional management personnel overcame organizational structure and cultural obstacles during the formation of a comprehensive campus-wide animal care OHSP. Steps toward establishing the animal care OHSP included assigning overall responsibility, identifying all stakeholders, creating a leadership group, and hiring a fulltime Animal Care OHSP Specialist. A web-based portal was developed, implemented, and refined over the past 7 y and reflected the unique organizational structures of the university and the needs of our research community. Through this web-based portal, hazards are identified, risks are assessed, and training is provided. The animal care OHSP now provides easy mandatory enrollment, supports timely feedback regarding hazards, and affords enrollees the opportunity to participate in voluntary medical surveillance. The future direction and development of the animal care OHSP will be based on the research trends of campus, identification of emerging health and safety hazards, and ongoing evaluation and refinement of the program.

Crash Simulation and Animation: 'A New Approach for Traffic Safety Analysis'

DOT National Transportation Integrated Search

2001-02-01

This researchs objective is to present a methodology to supplement the conventional traffic safety analysis techniques. This methodology aims at using computer simulation to animate and visualize crash occurrence at high-risk locations. This methodol...

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach.

PubMed

Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

2017-05-04

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. This article is copyright of The Authors, 2017.

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

PubMed Central

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

2014-01-01

It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

Targeted radionuclide therapy for lung cancer with iodine-131-labeled peptide in a nude-mouse model.

PubMed

Chen, Zhenzhu; Gao, Hongyi; Li, Man; Fang, Shun; Li, Guiping; Guo, Linlang

2017-06-01

Integrin α3β1 has been shown to be a novel candidate target for the imaging and specific therapy of non-small-cell lung cancer. We have previously reported on a peptide containing a novel motif of NGXG that specifically binds to the integrin α3 receptor on lung cancer cells using a one-bead one-peptide combinatorial library. In this study, we developed the peptide cNGEGQQc-based therapeutic agent labeling with radionuclide iodine-131 (I) and evaluated its characteristics including stability, biodistribution, antitumor activity, and safety. The results showed that I-cNGEGQQc was stable in serum. Furthermore, the biodistribution of I-cNGEGQQc was determined in normal mice and rabbits. In-vivo biodistribution studies showed that radiolabeled peptide in the kidney was significantly higher than that in other organs. Nude mice bearing lung cancer cell xenografts (H1975 and L78) were used as an in-vivo model for tumor-inhibition efficacy studies with I-cNGEGQQc. The tumor growth decreased significantly in mice receiving I-labeled peptide compared with the controls and the effect of I-labeled peptide can be blocked by unlabeled cNGEGQQc. Safety studies showed that I-cNGEGQQc was relatively safe for animals without significant toxicity. Our data suggest that I-cNGEGQQc has potential as a targeted radiotherapeutic agent for non-small-cell lung cancer.

Specific genetic modifications of domestic animals by gene targeting and animal cloning

PubMed Central

Wang, Bin; Zhou, Jiangfeng

2003-01-01

The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large livestock species until the successful creation of the first mammalian clone "Dolly" the sheep. The combination of the technologies for gene targeting of somatic cells with those of animal cloning made it possible to introduce specific genetic mutations into domestic animals. In this review, the principles of gene targeting in somatic cells and the challenges of nuclear transfer using gene-targeted cells are discussed. The relevance of gene targeting in domestic animals for applications in bio-medicine and agriculture are also examined. PMID:14614774

Development and validation of a real-time PCR assay for the detection of Toxoplasma gondii DNA in animal and meat samples.

PubMed

Marino, Anna Maria Fausta; Percipalle, Maurizio; Giunta, Renato Paolo; Salvaggio, Antonio; Caracappa, Giulia; Alfonzetti, Tiziana; Aparo, Alessandra; Reale, Stefano

2017-03-01

We report a rapid and reliable method for the detection of Toxoplasma gondii in meat and animal tissues based on real-time polymerase chain reaction (PCR). Samples were collected from cattle, small ruminants, horses, and pigs raised or imported into Sicily, Italy. All DNA preparations were assayed by real-time PCR tests targeted to a 98-bp long fragment in the AF 529-bp repeat element and to the B1 gene using specific primers. Diagnostic sensitivity (100%), diagnostic specificity (100%), limit of detection (0.01 pg), efficiency (92-109%), and precision (mean coefficient of variation = 0.60%), repeatability (100%), reproducibility (100%), and robustness were evaluated using 240 DNA extracted samples (120 positives and 120 negative as per the OIE nested PCR method) from different matrices. Positive results were confirmed by the repetition of both real-time and nested PCR assays. Our study demonstrates the viability of a reliable, rapid, and specific real-time PCR on a large scale to monitor contamination with Toxoplasma cysts in meat and animal specimens. This validated method can be used for postmortem detection in domestic and wild animals and for food safety purposes.

Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound ablation in the liver dome.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2014-12-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200-800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10°C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47°C-67°C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55°C vs. 42°C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Reconciling Horse Welfare, Worker Safety, and Public Expectations: Horse Event Incident Management Systems in Australia

PubMed Central

Fiedler, Julie M.; McGreevy, Paul D.

2016-01-01

Simple Summary Although often highly rewarding, human-horse interactions can also be dangerous. Using examples from equine and other contexts, this article acknowledges the growing public awareness of animal welfare, work underway towards safer equestrian workplaces, and the potential for adapting large animal rescue skills for the purposes of horse event incident management. Additionally, we identity the need for further research into communication strategies that address animal welfare and safety issues that arise when humans and horses interact in the workplace. Abstract Human-horse interactions have a rich tradition and can be highly rewarding, particularly within sport and recreation pursuits, but they can also be dangerous or even life-threatening. In parallel, sport and recreation pursuits involving animals, including horses, are facing an increased level of public scrutiny in relation to the use of animals for these purposes. However, the challenge lies with event organisers to reconcile the expectations of the public, the need to meet legal requirements to reduce or eliminate risks to paid and volunteer workers, and address horse welfare. In this article we explore incident management at horse events as an example of a situation where volunteers and horses can be placed at risk during a rescue. We introduce large animal rescue skills as a solution to improving worker safety and improving horse welfare outcomes. Whilst there are government and horse industry initiatives to improve safety and address animal welfare, there remains a pressing need to invest in a strong communication plan which will improve the safety of workplaces in which humans and horses interact. PMID:26927189

Laboratory Animal Workers' Attitudes and Perceptions Concerning Occupational Risk and Injury.

PubMed

Steelman, Eric D; Alexander, Jeffrey L

2016-01-01

Little is known regarding the risk perceptions and attitudes of laboratory animal care workers toward biologic safety. The purpose of this descriptive study was to assess the attitudes and perceptions of laboratory animal workers toward occupational and injury risk. Subscribers to the CompMed and TechLink listservs (n = 4808) were surveyed electronically, and 5.3% responded; data from 215 respondents were included in the final analysis. Primary variables of interest included AALAS certifications status, level of education, and responses to Likert-scale questions related to attitudes and perceptions of occupational risk and injury. Nonparametric (χ(2)) testing and measures of central tendency and dispersion were used to analyze and describe the data. According to 88.6% of respondents, biologic safety training is provided with information about zoonotic diseases of laboratory animals. Level of education was significantly related to perception of importance regarding wearing personal protective equipment. Participants indicated that appropriate support from coworkers and management staff is received, especially when performance and perception are hindered due to stress and fatigue. Laboratory animal staff are susceptible to injury and exposure to dangerous organisms and toxic substances. For this reason, to maximize safety, yearly biologic safety training should be provided, the importance of protective equipment adherence strengthened, and the culture of safety made a priority within the institution.

Microbicide safety/efficacy studies in animals: macaques and small animal models.

PubMed

Veazey, Ronald S

2008-09-01

A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

Microbicide Safety/Efficacy studies in animals -macaques and small animal models

PubMed Central

Veazey, Ronald S.

2009-01-01

Purpose of review A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. However, the unique host and cell specificity of HIV provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. Recent findings A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Summary Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a pre-requisite for advancing additional microbicide candidates to human clinical trials. PMID:19373023

SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation

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

Pasciak, A; Bradley, Y; Nodit, L

Purpose: To evaluate the feasibility of Yttrium-90 (90Y) radionuclide therapy as a potential treatment for obesity in a porcine model. As the only appetite-stimulating hormone, localized targeting of ghrelin-producing X/A cells in the fundus of the stomach using 90Y may reduce serum ghrelin levels and decrease hunger. Methods: Under approval of the University of Tennessee IACUC, 8 young female pigs aged 12–13 weeks and weighing 21.8–28.1 Kg were included in this study. Six animals underwent transfemoral angiography as part of a two-day procedure involving: (1) infusion of 99mTc-MAA, followed by nuclear scintigraphy and contrast-enhanced CT for treatment-planning and (2) administrationmore » of resin 90Y microspheres into the stomach fundus. Calibrated 90Y activities were infused into the main left gastric and the gastric artery arising from the splenic to yield predetermined fundal absorbed doses. Control animals underwent a sham procedure with saline and contrast. Weekly animal weight and serum ghrelin were measured along with post-euthanasia histologic analyses of mucosal integrity and ghrelin immunoreactive cell-density. Results: 90Y radioembolization was administered to six pigs in dosages from 46.3 to 105.1 MBq resulting in average fundal absorbed doses between 35.5 and 91.9 Gy. No animal showed any signs of pain or GI complication through the duration of the study. Ghrelin immunoreactive cell-density was significantly lower in treated vs. control animals in both the stomach fundus (13.5 vs 34.8, P < 0.05) and body (11.2 vs 19.8, P < 0.05). A trend towards decreased weight gain in treated animals as well as a decrease in explanted stomach volume was also noted. Conclusion: The safety and technical feasibility of radiation therapy using 90Y radioembolization as a potential treatment for obesity has been demonstrated at fundal absorbed doses over 90 Gy. Preliminary data is suggestive of short-term safety and potential efficacy, however, further animal studies are required. Project was funded by SIRTex medical ltd.« less

Animal models for periodontal regeneration and peri-implant responses.

PubMed

Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

2015-06-01

Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

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

Ryan, Patricia C., E-mail: ryanp@medimmune.com; Sleeman, Matthew A.; Rebelatto, Marlon

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters othermore » than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys. • Lung changes observed reflect role of GM-CSF in alveolar macrophage function. • High safety margins support continued clinical development of mavrilimumab.« less

SAFETY GUIDES FOR YOU--IN THE PRIMARY GRADES.

ERIC Educational Resources Information Center

WALKER, LUVERNE CRABTREE

THIS SAFETY INSTRUCTIONAL GUIDE FOR PRIMARY-GRADE TEACHERS PRESENTS NINE DIFFERENT SAFETY UNITS, INCLUDING TRAFFIC SAFETY, PLAYTIME SAFETY, SAFE EATING AND DRINKING HABITS, SAFE CLOTHING, HOME SAFETY, ANIMAL SAFETY, CIVIL DEFENSE SECURITY, AND TESTING SAFETY PRACTICES. EACH UNIT STRESSES THE REASONS FOR ACCENTING SAFETY, WHAT TO KNOW AND DO, AND…

Safe and stable noninvasive focal gene delivery to the mammalian brain following focused ultrasound.

PubMed

Stavarache, Mihaela A; Petersen, Nicholas; Jurgens, Eric M; Milstein, Elizabeth R; Rosenfeld, Zachary B; Ballon, Douglas J; Kaplitt, Michael G

2018-04-27

OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation. The objective of the current study was to evaluate the efficiency, safety, and long-term stability of MRgFUS-mediated noninvasive gene therapy in the mammalian brain. METHODS Focused ultrasound under the control of MRI, in combination with microbubbles consisting of albumin-coated gas microspheres, was applied to rat striatum, followed by intravenous infusion of an adeno-associated virus serotype 1/2 (AAV1/2) vector expressing green fluorescent protein (GFP) as a marker. Following recovery, animals were followed from several hours up to 15 months. Immunostaining for GFP quantified transduction efficiency and stability of expression. Quantification of neuronal markers was used to determine histological safety over time, while inflammatory markers were examined for evidence of immune responses. RESULTS Transitory disruption of the BBB by MRgFUS resulted in efficient delivery of the AAV1/2 vector to the targeted rodent striatum, with 50%-75% of striatal neurons transduced on average. GFP transgene expression appeared to be stable over extended periods of time, from 2 weeks to 6 months, with evidence of ongoing stable expression as long as 16 months in a smaller cohort of animals. No evidence of substantial toxicity, tissue injury, or neuronal loss was observed. While transient inflammation from BBB disruption alone was noted for the first few days, consistent with prior observations, no evidence of brain inflammation was observed from 2 weeks to 6 months following MRgFUS BBB opening, despite delivery of a virus and expression of a foreign protein in target neurons. CONCLUSIONS This study demonstrates that transitory BBB disruption using MRgFUS can be a safe and efficient method for site-specific delivery of viral vectors to the brain, raising the potential for noninvasive focal human gene therapy for neurological disorders.

A critical assessment of the scientific basis, and implementation, of regulations for the safety assessment and marketing of innovative tobacco-related products.

PubMed

Combes, Robert D; Balls, Michael

2015-09-01

Our scientific, logistical, ethical and animal welfare-related concerns about the latest US Food and Drug Administration (FDA) regulations for existing and so-called 'new' tobacco products, aimed at reducing harmful exposures, are explained. Such claims for sales in the USA now have to be based on a wide range of information, a key part of which will increasingly be data on safety and risk. One of the pathways to achieve marketing authorisation is to demonstrate substantial equivalence (SE) with benchmark products, called predicates. However, the regulations are insufficiently transparent with regard to: a) a rationale for the cut-off date for 'old' and 'new' products, and for exempting the former from regulation; b) the scientific validity and operation of SE; c) options for product labelling to circumvent SE; d) the experimental data required to support, and criteria to judge, a claim; and e) a strategy for risk assessment/management. Scientific problems related to the traditional animal methods used in respiratory disease and inhalation toxicology, and the use of quantitative comparators of toxicity, such as the No Observed Adverse Effect Level, are discussed. We review the advantages of relevant in vitro, mechanism-based, target tissue-oriented technologies, which an advisory report of the Institute of Medicine of the US National Academy of Sciences largely overlooked. These benefits include: a) the availability, for every major site in the respiratory tract, of organotypic human cell-based tissue culture systems, many of which are already being used by the industry; b) the accurate determination of concentrations of test materials received by target cells; c) methods for exposure to particulate and vapour phases of smoke, separately or combined; d) the ability to study tissue-specific biotransformation; and e) the use of modern, human-focused methodologies, unaffected by species differences. How data extrapolation, for risk assessment, from tissue culture to the whole animal, could be addressed, is also discussed. A cost (to animal welfare)-benefit (to society, including industry and consumers) analysis was conducted, taking into account the above information; the potential for animal suffering; the extensive data already available; the existence of other, less hazardous forms of nicotine delivery; the fact that much data will be generated solely for benchmarking; and that many smokers (especially nicotine-dependents) ignore health warnings. It is concluded that, in common with policies of several tobacco companies and countries, the use of laboratory animals for tobacco testing is very difficult, if not impossible, to justify. Instead, we propose and argue for an integrated testing scheme, starting with extensive chemical analysis of the ingredients and by-products associated with the use of tobacco products and their toxicity, followed by use of in vitro systems and early clinical studies (involving specific biomarkers) with weight-of-evidence assessments at each stage. Appropriate adjustment factors could be developed to enable concentration-response data obtained in vitro, with the other information generated by the strategy, to enable the FDA to meet its objectives. It is hoped that our intentionally provocative ideas will stimulate further debate on this contentious area of regulatory testing and public safety. 2015 FRAME.

The evolution of recombinant thrombolytics: Current status and future directions

PubMed Central

Adivitiya; Khasa, Yogender Pal

2017-01-01

ABSTRACT Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration. PMID:27696935

Developmental toxicity testing of monoclonal antibodies: an enhanced pre- and postnatal study design option.

PubMed

Stewart, Jane

2009-09-01

For many monoclonal antibodies (mAb), the preferred species for general and reproductive safety testing is often the cynomolgus monkey. This article describes the rationale for combining the traditional "segmented" embryofetal development study with the pre- and postnatal development (PPND) study into a single "enhanced" PPND study design in the cynomolgus monkey where a single cohort of animals is exposed throughout gestation and allowed to give birth naturally. The proposed "enhanced" PPND study design evaluates all the stages of the traditional two study design using fewer animals. It also assesses the functional consequences of mid to late gestational exposure. This is of particular relevance to the risk assessment of monoclonal antibodies where fetal exposure to maternal IgG increases as pregnancy progresses and where morphologic examination of a pre-term fetus may not be adequate to reveal the presence of adverse effects on functional development of key target organs.

The Role of Veterinary Education in Safety Policies for Animal-Assisted Therapy and Activities in Hospitals and Nursing Homes.

PubMed

Linder, Deborah E; Mueller, Megan K; Gibbs, Debra M; Siebens, Hannah C; Freeman, Lisa M

Animal-assisted activities (AAA) and animal-assisted therapy (AAT) programs are increasing in popularity, but current programs vary in their safety and health policies. Veterinarians can have an important role in ensuring the safety of both the animals and humans involved, but it is unclear how best to educate veterinary students to serve effectively in this role. Therefore, the goal of this study was to assess the knowledge gaps and perceptions of first-year veterinary students on health and safety aspects of AAA/AAT programs by administering a survey. This information could then guide future educational training in veterinary schools to address the knowledge gaps in this area. Formal education during the veterinary curriculum had not yet been provided to these students on AAA/AAT before the survey. Of 98 first-year veterinary students, 91 completed the survey. When asked about policies on visiting animals, 58% of students responded that nursing homes are required to have a policy and 67% responded that hospitals are required to have one. Three quarters of students reported that veterinarians, animal handlers, and facilities should share the responsibility for ensuring safe human-animal interaction in AAA/AAT programs. Most (82%) of the students responded that all or most national and local therapy animal groups prohibit animals that consume raw meat diets from participating in AAA/AAT programs. The results of this survey will help veterinary schools better identify knowledge gaps that can be addressed in veterinary curricula so future veterinarians will be equipped to provide appropriate public health information regarding AAA/AAT programs.

Conditions of transfer and quality of food.

PubMed

Southern, K J; Rasekh, J G; Hemphill, F E; Thaler, A M

2006-08-01

Many factors contribute to the production of safe foods of animal origin. Initiatives for an integrated approach to food safety recognise the importance of optimising transportation conditions to ensure on-farm interventions are preserved. Physical, microbial, and environmental hazards during the transportation process may adversely affect the safety and quality of meat, poultry, and egg products. Additionally, the stress level in animals can be raised by transportation conditions, potentially causing increased pathogen shedding in carrier animals which exposes other animals to possible contamination. The physiological effects of stress on animals can reduce the quality of meat, poultry, and egg products produced by the animals, thus decreasing the economic value of the animal. Increased globalisation of markets provides an incentive for transportation standards of food animals within a country as well as transportation standards between countries.

Dangerous animals capture and maintain attention in humans.

PubMed

Yorzinski, Jessica L; Penkunas, Michael J; Platt, Michael L; Coss, Richard G

2014-05-28

Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous animals (distractors) as well as detected images of a nondangerous animal (target) among arrays of dangerous animals (distractors). We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

Do Performance-Safety Tradeoffs Cause Hypometric Metabolic Scaling in Animals?

PubMed

Harrison, Jon F

2017-09-01

Hypometric scaling of aerobic metabolism in animals has been widely attributed to constraints on oxygen (O 2 ) supply in larger animals, but recent findings demonstrate that O 2 supply balances with need regardless of size. Larger animals also do not exhibit evidence of compensation for O 2 supply limitation. Because declining metabolic rates (MRs) are tightly linked to fitness, this provides significant evidence against the hypothesis that constraints on supply drive hypometric scaling. As an alternative, ATP demand might decline in larger animals because of performance-safety tradeoffs. Larger animals, which typically reproduce later, exhibit risk-reducing strategies that lower MR. Conversely, smaller animals are more strongly selected for growth and costly neurolocomotory performance, elevating metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

A pre-clinical safety study of PEGylated recombinant human endostatin (M2ES) in Sprague Dawley rats.

PubMed

Geng, Xingchao; Guo, Lifang; Liu, Li; Wang, Chao; Peng, Qian; Qi, Weihong; Sun, Li; Liu, Xiaomeng; Miao, Yufa; Lin, Zhi; Fu, Yan; Luo, Yongzhang; Li, Bo

2018-06-01

PEGylated recombinant human endostatin (M 2 ES) exhibited prolonged serum half-life and enhanced antitumor activity when compared with endostatin. A pre-clinical study was performed to evaluate the safety of M 2 ES in rats. After intravenous (IV) infusions of M 2 ES at a dose level of 3, 15 and 75 mg/kg in Sprague Dawley (SD) rats, M 2 ES was well tolerated in animals, with no observable changes in clinical observation, body weight, food consumption, urine analysis, hematology and serum biochemical analysis. The increase of kidney weights, and slight to severe vacuolation and necrosis of proximal tubule epithelial cells in kidney were observed in 15 and 75 mg/kg M 2 ES groups, but this adverse-effect was reversible. In summary, the major toxicity target organ of M 2 ES might be kidney, and the no observed adverse effect level (NOAEL) of M 2 ES in rats was 3 mg/kg in this study. These pre-clinical safety data contribute to the initiation of the ongoing clinical study. Copyright © 2018. Published by Elsevier Inc.

Pesticides and Animal Health

Science.gov Websites

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Challenges of Sanitary Compliance Related to Trade in Products of Animal Origin in Southern Africa.

PubMed

Magwedere, Kudakwashe; Songabe, Tembile; Dziva, Francis

2015-06-30

Irrespective of the existence of potentially pathogenic organisms carried by animals, foods of animal origin remain the prime nutrition of humans world-wide. As such, food safety continues to be a global concern primarily to safeguard public health and to promote international trade. Application of integrated risk-based quality assurance procedures on-farm and at slaughterhouses plays a crucial role in controlling hazards associated with foods of animal origin. In the present paper we examine safety assurance systems and associated value chains for foods of animal origin based on historical audit results of some Southern African countries with thriving export trade in animal products, mainly to identify areas for improvement. Among the key deficiencies identified were: i) failure to keep pace with scientific advances related to the ever-changing food supply chain; ii) lack of effective national and regional intervention strategies to curtail pathogen transmission and evolution, notably the zoonotic Shiga toxin-producing Escherichia coli ; and iii) a lack of effective methods to reduce contamination of foods of wildlife origin. The introduction of foods of wildlife origin for domestic consumption and export markets seriously compounds already existing conflicts in legislation governing food supply and safety. This analysis identifies gaps required to improve the safety of foods of wildlife origin.

Challenges of Sanitary Compliance Related to Trade in Products of Animal Origin in Southern Africa

PubMed Central

Magwedere, Kudakwashe; Songabe, Tembile

2015-01-01

Irrespective of the existence of potentially pathogenic organisms carried by animals, foods of animal origin remain the prime nutrition of humans world-wide. As such, food safety continues to be a global concern primarily to safeguard public health and to promote international trade. Application of integrated risk-based quality assurance procedures on-farm and at slaughterhouses plays a crucial role in controlling hazards associated with foods of animal origin. In the present paper we examine safety assurance systems and associated value chains for foods of animal origin based on historical audit results of some Southern African countries with thriving export trade in animal products, mainly to identify areas for improvement. Among the key deficiencies identified were: i) failure to keep pace with scientific advances related to the ever-changing food supply chain; ii) lack of effective national and regional intervention strategies to curtail pathogen transmission and evolution, notably the zoonotic Shiga toxin-producing Escherichia coli; and iii) a lack of effective methods to reduce contamination of foods of wildlife origin. The introduction of foods of wildlife origin for domestic consumption and export markets seriously compounds already existing conflicts in legislation governing food supply and safety. This analysis identifies gaps required to improve the safety of foods of wildlife origin. PMID:27800409

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 392.9 - Availability of additional guidance.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 392.9 Section 392.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOOD SAFETY AND INSPECTION SERVICE ADMINISTRATIVE PROVISIONS PETITIONS FOR RULEMAKING § 392.9... rulemaking may be found on the FSIS Web site at http://www/fsis.usda.gov/. ...

9 CFR 430.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... poultry product that is in a form that is edible without additional preparation to achieve food safety and... Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY... product safe for human consumption. Examples of lethality treatments are cooking or the application of an...

Genome editing in pluripotent stem cells: research and therapeutic applications.

PubMed

Deleidi, Michela; Yu, Cong

2016-05-06

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans.

PubMed

Bezdjian, Aren; Kraaijenga, Véronique J C; Ramekers, Dyan; Versnel, Huib; Thomeer, Hans G X M; Klis, Sjaak F L; Grolman, Wilko

2016-11-26

Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53%) was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%). Ciliary neurotrophic factor (50%), nerve growth factor (24%) and insulin-like growth factor (21%) were most often used. Injection site reaction was a frequently occurring adverse event (61%) followed by asthenia (24%) and gastrointestinal disturbances (20%). Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising.

The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

PubMed

O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

2016-07-01

The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. Copyright © 2016 Elsevier Inc. All rights reserved.

Biosonar behaviour of free-ranging porpoises

PubMed Central

Akamatsu, Tomonari; Wang, Ding; Wang, Kexiong; Naito, Yasuhiko

2005-01-01

Detecting objects in their paths is a fundamental perceptional function of moving organisms. Potential risks and rewards, such as prey, predators, conspecifics or non-biological obstacles, must be detected so that an animal can modify its behaviour accordingly. However, to date few studies have considered how animals in the wild focus their attention. Dolphins and porpoises are known to actively use sonar or echolocation. A newly developed miniature data logger attached to a porpoise allows for individual recording of acoustical search efforts and inspection distance based on echolocation. In this study, we analysed the biosonar behaviour of eight free-ranging finless porpoises (Neophocaena phocaenoides) and demonstrated that these animals inspect the area ahead of them before swimming silently into it. The porpoises inspected distances up to 77 m, whereas their swimming distance without using sonar was less than 20 m. The inspection distance was long enough to ensure a wide safety margin before facing real risks or rewards. Once a potential prey item was detected, porpoises adjusted their inspection distance from the remote target throughout their approach. PMID:15888412

Ethical research as the target of animal extremism: an international problem.

PubMed

Conn, P Michael; Rantin, F T

2010-02-01

Animal extremism has been increasing worldwide; frequently researchers are the targets of actions by groups with extreme animal rights agendas. Sometimes this targeting is violent and may involve assaults on family members or destruction of property. In this article, we summarize recent events and suggest steps that researchers can take to educate the public on the value of animal research both for people and animals.

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (a) Any person desiring to process an exotic animal, exotic animal carcasses, exotic animal meat and... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Application by official exotic animal establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND...

Data-driven risk models could help target pipeline safety inspections

DOT National Transportation Integrated Search

2008-07-01

Federal safety agencies share a common problemthe : need to target resources effectively to reduce risk. One : way this targeting is commonly done is with a risk model : that uses safety data along with expert judgment to identify : and weight ris...

9 CFR 352.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Definitions. 352.1 Section 352.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.1 Definitions. The...

Biological safety concepts of genetically modified live bacterial vaccines.

PubMed

Frey, Joachim

2007-07-26

Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment includes knowledge of the precise function and genetic location of the genes to be mutated, their genetic stability, potential reversion mechanisms, possible recombination events with dormant genes, gene transfer to other organisms as well as gene acquisition from other organisms by phage transduction, transposition or plasmid transfer and cis- or trans-complementation. For this, GMOs that are constructed with modern techniques of genetic engineering display a significant advantage over random mutagenesis derived live organisms. The selection of suitable GMO candidate strains can be made under in vitro conditions using basic knowledge on molecular mechanisms of pathogenicity of the corresponding bacterial species rather than by in vivo testing of large numbers of random mutants. This leads to a more targeted safety testing on volunteers and to a reduction in the use of animal experimentation.

Opportunities to Apply the 3Rs in Safety Assessment Programs

PubMed Central

Sewell, Fiona; Edwards, Joanna; Prior, Helen; Robinson, Sally

2016-01-01

Abstract Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans. PMID:28053076

9 CFR 417.4 - Validation, Verification, Reassessment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... not have a HACCP plan because a hazard analysis has revealed no food safety hazards that are.... 417.4 Section 417.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... ACT HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.4 Validation, Verification...

9 CFR 417.4 - Validation, Verification, Reassessment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... not have a HACCP plan because a hazard analysis has revealed no food safety hazards that are.... 417.4 Section 417.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... ACT HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.4 Validation, Verification...

9 CFR 417.4 - Validation, Verification, Reassessment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... not have a HACCP plan because a hazard analysis has revealed no food safety hazards that are.... 417.4 Section 417.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... ACT HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.4 Validation, Verification...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 352.17 - Transportation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Transportation. 352.17 Section 352.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.17 Transportation. This shall...

9 CFR 352.17 - Transportation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Transportation. 352.17 Section 352.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.17 Transportation. This shall...

9 CFR 352.17 - Transportation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Transportation. 352.17 Section 352.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.17 Transportation. This shall...

9 CFR 352.17 - Transportation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Transportation. 352.17 Section 352.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.17 Transportation. This shall...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

EPA Pesticide Factsheets

EPA News Release: IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

Identify and Translate Learnings from On-Going Assay ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

20170228 - Identify and Translate Learnings from On-Going ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

9 CFR 107.2 - Products under State license.

Code of Federal Regulations, 2010 CFR

2010-01-01

... establishments that produce such products; and (2) The State has the authority to review the purity, safety... to review product test results to assure compliance with applicable standards of purity, safety, and... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Products under State license. 107.2...

Adverse Outcome Pathways can drive non-animal approaches for safety assessment

PubMed Central

Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

2015-01-01

Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

Food Supply and Food Safety Issues in China

PubMed Central

Lam, Hon-Ming; Remais, Justin; Fung, Ming-Chiu; Xu, Liqing; Sun, Samuel Sai-Ming

2013-01-01

Food supply and food safety are major global public health issues, and are particularly important in heavily populated countries such as China. Rapid industrialisation and modernisation in China are having profound effects on food supply and food safety. In this Review, we identified important factors limiting agricultural production in China, including conversion of agricultural land to other uses, freshwater deficits, and soil quality issues. Additionally, increased demand for some agricultural products is examined, particularly those needed to satisfy the increased consumption of animal products in the Chinese diet, which threatens to drive production towards crops used as animal feed. Major sources of food poisoning in China include pathogenic microorganisms, toxic animals and plants entering the food supply, and chemical contamination. Meanwhile, two growing food safety issues are illegal additives and contamination of the food supply by toxic industrial waste. China’s connections to global agricultural markets are also having important effects on food supply and food safety within the country. Although the Chinese Government has shown determination to reform laws, establish monitoring systems, and strengthen food safety regulation, weak links in implementation remain. PMID:23746904

The SEURAT-1 approach towards animal free human safety assessment.

PubMed

Gocht, Tilman; Berggren, Elisabet; Ahr, Hans Jürgen; Cotgreave, Ian; Cronin, Mark T D; Daston, George; Hardy, Barry; Heinzle, Elmar; Hescheler, Jürgen; Knight, Derek J; Mahony, Catherine; Peschanski, Marc; Schwarz, Michael; Thomas, Russell S; Verfaillie, Catherine; White, Andrew; Whelan, Maurice

2015-01-01

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health.The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built on three levels:(i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological mode-of-actions leading to adverse outcomes (addressing mainly liver toxicity);(ii)adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects (i.e., those related to the adverse outcome pathway descriptions);(iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term, it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios are addressed with case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from designing the case studies and is discussed in the context of international developments focusing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing.

9 CFR 352.16 - Exports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Exports. 352.16 Section 352.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION EXOTIC ANIMALS AND HORSES; VOLUNTARY INSPECTION Exotic Animals § 352.16 Exports. This shall be...

Occupational health and safety aspects of animal handling in dairy production.

PubMed

Lindahl, Cecilia; Lundqvist, Peter; Hagevoort, G Robert; Lunner Kolstrup, Christina; Douphrate, David I; Pinzke, Stefan; Grandin, Temple

2013-01-01

Livestock handling in dairy production is associated with a number of health and safety issues. A large number of fatal and nonfatal injuries still occur when handling livestock. The many animal handling tasks on a dairy farm include moving cattle between different locations, vaccination, administration of medication, hoof care, artificial insemination, ear tagging, milking, and loading onto trucks. There are particular problems with bulls, which continue to cause considerable numbers of injuries and fatalities in dairy production. In order to reduce the number of injuries during animal handling on dairy farms, it is important to understand the key factors in human-animal interactions. These include handler attitudes and behavior, animal behavior, and fear in cows. Care when in close proximity to the animal is the key for safe handling, including knowledge of the flight zone, and use of the right types of tools and suitable restraint equipment. Thus, in order to create safe working conditions during livestock handling, it is important to provide handlers with adequate training and to establish sound safety management procedures on the farm.

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

PubMed

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization this information should be complemented by a clear clinical proof of safety. The ongoing outsourcing process of Regulatory Safety Pharmacology activities from large Pharmas to contract research organizations should be taken as an opportunity to establish long-overdue in-house Exploratory Safety Pharmacology units fully dedicated to the optimization of clinical candidates on organ safety.

Bear Spray Safety Program

USGS Publications Warehouse

Blome, C.D.; Kuzniar, R.L.

2009-01-01

A bear spray safety program for the U.S. Geological Survey (USGS) was officially initiated by the Firearms Safety Committee to address accident prevention and to promote personnel training in bear spray and its transportation, storage, and use for defense against wild animals. Used as part of a system including firearms, or used alone for those who choose not to carry a firearm, bear spray is recognized as an effective tool that can prevent injury in a wild animal attack.

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

9 CFR 319.703 - Rendered animal fat or mixture thereof.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Rendered animal fat or mixture thereof. 319.703 Section 319.703 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

9 CFR 319.703 - Rendered animal fat or mixture thereof.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rendered animal fat or mixture thereof. 319.703 Section 319.703 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2010 CFR

2010-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2012 CFR

2012-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2011 CFR

2011-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2014 CFR

2014-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2013 CFR

2013-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2011 CFR

2011-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2013 CFR

2013-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2012 CFR

2012-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2014 CFR

2014-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 311.27 - Injured animals slaughtered at unusual hours.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Injured animals slaughtered at unusual hours. 311.27 Section 311.27 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT... AND VOLUNTARY INSPECTION AND CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND...

Overcoming preexisting humoral immunity to AAV using capsid decoys.

PubMed

Mingozzi, Federico; Anguela, Xavier M; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J; Hui, Daniel J; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser; High, Katherine A

2013-07-17

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.

Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys

PubMed Central

Anguela, Xavier M.; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J.; Hui, Daniel J.; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J.; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M.; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser

2014-01-01

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery. PMID:23863832

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

The use of non-animal alternatives in the safety evaluations of cosmetics ingredients by the Scientific Committee on Consumer Safety (SCCS).

PubMed

Vinardell, M P

2015-03-01

In Europe, the safety evaluation of cosmetics is based on the safety evaluation of each individual ingredient. Article 3 of the Cosmetics Regulation specifies that a cosmetic product made available on the market is to be safe for human health when used normally or under reasonably foreseeable conditions. For substances that cause some concern with respect to human health (e.g., colourants, preservatives, UV-filters), safety is evaluated at the Commission level by a scientific committee, presently called the Scientific Committee on Consumer Safety (SCCS). According to the Cosmetics Regulations, in the EU, the marketing of cosmetics products and their ingredients that have been tested on animals for most of their human health effects, including acute toxicity, is prohibited. Nevertheless, any study dating from before this prohibition took effect is accepted for the safety assessment of cosmetics ingredients. The in vitro methods reported in the dossiers submitted to the SCCS are here evaluated from the published reports issued by the scientific committee of the Directorate General of Health and Consumers (DG SANCO); responsible for the safety of cosmetics ingredients. The number of studies submitted to the SCCS that do not involve animals is still low and in general the safety of cosmetics ingredients is based on in vivo studies performed before the prohibition. Copyright © 2014 Elsevier Inc. All rights reserved.

The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models

PubMed Central

Vernetti, Lawrence; Bergenthal, Luke; Shun, Tong Ying; Taylor, D. Lansing

2016-01-01

Abstract Microfluidic human organ models, microphysiology systems (MPS), are currently being developed as predictive models of drug safety and efficacy in humans. To design and validate MPS as predictive of human safety liabilities requires safety data for a reference set of compounds, combined with in vitro data from the human organ models. To address this need, we have developed an internet database, the MPS database (MPS-Db), as a powerful platform for experimental design, data management, and analysis, and to combine experimental data with reference data, to enable computational modeling. The present study demonstrates the capability of the MPS-Db in early safety testing using a human liver MPS to relate the effects of tolcapone and entacapone in the in vitro model to human in vivo effects. These two compounds were chosen to be evaluated as a representative pair of marketed drugs because they are structurally similar, have the same target, and were found safe or had an acceptable risk in preclinical and clinical trials, yet tolcapone induced unacceptable levels of hepatotoxicity while entacapone was found to be safe. Results demonstrate the utility of the MPS-Db as an essential resource for relating in vitro organ model data to the multiple biochemical, preclinical, and clinical data sources on in vivo drug effects. PMID:28781990

Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

PubMed

Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

2013-12-01

Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

9 CFR 325.9 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false [Reserved] 325.9 Section 325.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION TRANSPORTATION § 325.9 [Reserved] ...

Pesticide Information for Veterinarians

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Home Page Pesticide Health and Safety Information Pesticides and Animal Health Pesticide Information

9 CFR 318.10 - Prescribed treatment of pork and products containing pork to destroy trichinae.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Agriculture Building, Food Safety and Inspection Service, U.S. Department of Agriculture, Washington, DC 20250..., Food Safety and Inspection Service, U.S. Department of Agriculture, Washington, DC 20250 or at the... products containing pork to destroy trichinae. 318.10 Section 318.10 Animals and Animal Products FOOD...

Read Across Approaches: Chemical Structure and Bioactivity ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN and ILSI workshop on Workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN and ILSI workshop on Workshop: State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

Improving animal research facility operations through the application of lean principles.

PubMed

Khan, Nabeel; Umrysh, Brian M

2008-06-01

Animal research is a vital component of US research and well-functioning animal research facilities are critical both to the research itself and to the housing and feeding of the animals. The Office of Animal Care (OAC) at Seattle Children's Hospital Research Institute realized it had to improve the efficiency and safety of its animal research facility (ARF) to prepare for expansion and to advance the Institute's mission. The main areas for improvement concerned excessive turnaround time to process animal housing and feeding equipment; the movement and flow of equipment and inventory; and personnel safety. To address these problems, management held two process improvement workshops to educate employees about lean principles. In this article we discuss the application of these principles and corresponding methods to advance Children's Research Institute's mission of preventing, treating, and eliminating childhood diseases.

Trade and food safety aspects for animal influenza viruses

USDA-ARS?s Scientific Manuscript database

The World Organization for Animal Health provides sanitary standards for international trade and emphasizes science-based risk assessment for safe trade of animals and animal products. The goal is to prevent unacceptable risks to animal and human health while avoiding unjustified or politically mot...

Management of occupational health risks in small-animal veterinary practices.

PubMed

D'Souza, Eva; Barraclough, Richard; Fishwick, David; Curran, Andrew

2009-08-01

Small-animal work is a major element of veterinary practice in the UK and may be hazardous, with high levels of work-related injuries and ill-health reported in Australia and USA. There are no studies addressing the management of occupational health risks arising from small-animal work in the UK. To investigate the sources of health and safety information used and how health and safety and 12 specific occupational health risks are managed by practices. A cross-sectional postal survey of all small-animal veterinary practices in Hampshire. A response was mandatory as this was a Health & Safety Executive (HSE) inspection activity. A total of 118 (100%) practices responded of which 93 were eligible for inclusion. Of these, 99 and 86%, respectively, were aware of the Royal College of Veterinary Surgeons (RCVS) practice standards and had British Small Animal Veterinary Association (BSAVA) staff members, while only 51% had previous contact with HSE (publications, advice and visit). Ninety per cent had health and safety policies, but only 31% had trained responsible staff in health and safety. Specific health hazards such as occupational allergens and computer use were relatively overlooked both by practices and the RCVS/BSAVA guidance available in 2002. Failings in active health risk management systems could be due to a lack of training to ensure competence in those with responsibilities. Practices rely on guidance produced by their professional bodies. Current RCVS guidance, available since 2005, has remedied some previous omissions, but further improvements are recommended.

Current Status of the Preharvest Application of Pro- and Prebiotics to Farm Animals to Enhance the Microbial Safety of Animal Products.

PubMed

Joerger, Rolf D; Ganguly, Arpeeta

2017-01-01

The selection of microorganisms that act as probiotics and feed additives that act as prebiotics is an ongoing research effort, but a sizable range of commercial pro-, pre- and synbiotic (combining pro- and prebiotics) products are already available and being used on farms. A survey of the composition of commercial products available in the United States revealed that Lactobacillus acidophilus, Enterococcus faecium, and Bacillus subtilis were the three most common species in probiotic products. Of the nearly 130 probiotic products (also called direct-fed microbials) for which information was available, about 50 also contained yeasts or molds. The focus on these particular bacteria and eukaryotes is due to long-standing ideas about the benefits of such strains, research data on effectiveness primarily in laboratory or research farm settings, and regulations that dictate which microorganisms or feed additives can be administered to farm animals. Of the direct-fed microbials, only six made a claim relating to food safety or competitive exclusion of pathogens. None of the approximately 50 prebiotic products mentioned food safety in their descriptions. The remainder emphasized enhancement of animal performance such as weight gain or overall animal health. The reason why so few products carry food safety-related claims is the difficulties in establishing unambiguous cause and effect relationships between the application of such products in varied and constantly changing farm environments and improved food safety of the end product.

Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.

PubMed

Toepp, Angela; Larson, Mandy; Grinnage-Pulley, Tara; Bennett, Carolyne; Anderson, Michael; Parrish, Molly; Fowler, Hailie; Wilson, Geneva; Gibson-Corely, Katherine; Gharpure, Radhika; Cotter, Caitlin; Petersen, Christine

2018-05-01

In Leishmania infantum -endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum , the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec ® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

Real-Time Target Motion Animation for Missile Warning System Testing

DTIC Science & Technology

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

Food Safety and Quality: Who Does What in the Federal Government, Volume 1

DTIC Science & Technology

1990-12-01

effectiveness of animal drugs and feeds: feeds safety of food animals 26 244 US DA ~-- ~.---- FS!S Meat and poultry FMIA Safety/quality of meat and...products are marketed; "* reviews and assesses the effectiveness of state meat and poultry inspec- A tion programs for plants under state jurisdiction to...decreased between 1981 and 1989. We did not evaluate the impact that the changes in funding, staffing, and work load had on the effectiveness of the

Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

PubMed

Rissmann, M; Ulrich, R; Schröder, C; Hammerschmidt, B; Hanke, D; Mroz, C; Groschup, M H; Eiden, M

2017-01-23

Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Eating nanomaterials: cruelty-free and safe? the EFSA guidance on risk assessment of nanomaterials in food and feed.

PubMed

Sauer, Ursula G

2011-12-01

Nanomaterials are increasingly being added to food handling and packaging materials, or directly, to human food and animal feed. To ensure the safety of such engineered nanomaterials (ENMs), in May 2011, the European Food Safety Authority (EFSA) published a guidance document on Risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain. It states that risk assessment should be performed by following a step-wise procedure. Whenever human or animal exposure to nanomaterials is expected, the general hazard characterisation scheme requests information from in vitro genotoxicity, toxicokinetic and repeated dose 90-day oral toxicity studies in rodents. Numerous prevailing uncertainties with regard to nanomaterial characterisation and their hazard and risk assessment are addressed in the guidance document. This article discusses the impact of these knowledge gaps on meeting the goal of ensuring human safety. The EFSA's guidance on the risk assessment of ENMs in food and animal feed is taken as an example for discussion, from the point of view of animal welfare, on what level of uncertainty should be considered acceptable for human safety assessment of products with non-medical applications, and whether animal testing should be considered ethically acceptable for such products.

Linking live animals and products: traceability.

PubMed

Britt, A G; Bell, C M; Evers, K; Paskin, R

2013-08-01

It is rarely possible to successfully contain an outbreak of an infectious animal disease, or to respond effectively to a chemical residue incident, without the use of a system for identifying and tracking animals. The linking of animals at the time they are slaughtered--through the use of identification devices or marks and accompanying movement documentation--with the meat produced from their carcasses, adds further value from the perspective of consumer safety. Over the past decade, animal identification technology has become more sophisticated and affordable. The development of the Internet and mobile communication tools, complemented bythe expanded capacity of computers and associated data management applications, has added a new dimension to the ability of Competent Authorities and industry to track animals and the food they produce for disease control, food safety and commercial purposes.

Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies.

PubMed

Prior, Helen; Bottomley, Anna; Champéroux, Pascal; Cordes, Jason; Delpy, Eric; Dybdal, Noel; Edmunds, Nick; Engwall, Mike; Foley, Mike; Hoffmann, Michael; Kaiser, Robert; Meecham, Ken; Milano, Stéphane; Milne, Aileen; Nelson, Rick; Roche, Brian; Valentin, Jean-Pierre; Ward, Gemma; Chapman, Kathryn

2016-01-01

The Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing of non-rodents during telemetry recordings in safety pharmacology and toxicology studies. The aim was to share experiences, canvas opinion on the study procedures/designs that could be used and explore the barriers to social housing. Thirty-nine sites, either running studies (Sponsors or Contract Research Organisations, CROs) and/or outsourcing work responded to the survey (51% from Europe; 41% from USA). During safety pharmacology studies, 84, 67 and 100% of respondents socially house dogs, minipigs and non-human primates (NHPs) respectively on non-recording days. However, on recording days 20, 20 and 33% of respondents socially house the animals, respectively. The main barriers for social housing were limitations in the recording equipment used, study design and animal temperament/activity. During toxicology studies, 94, 100 and 100% of respondents socially house dogs, minipigs and NHPs respectively on non-recording days. However, on recording days 31, 25 and 50% of respondents socially house the animals, respectively. The main barriers for social housing were risk of damage to and limitations in the recording equipment used, food consumption recording and temperament/activity of the animals. Although the majority of the industry does not yet socially house animals during telemetry recordings in safety pharmacology and toxicology studies, there is support to implement this refinement. Continued discussions, sharing of best practice and data from companies already socially housing, combined with technology improvements and investments in infrastructure are required to maintain the forward momentum of this refinement across the industry. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

PubMed Central

Choi, K. Yeon; Root, Matthew

2016-01-01

ABSTRACT Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection. PMID:27334585

Transcranial Direct Current Stimulation in Epilepsy.

PubMed

San-Juan, Daniel; Morales-Quezada, León; Orozco Garduño, Adolfo Josué; Alonso-Vanegas, Mario; González-Aragón, Maricarmen Fernández; Espinoza López, Dulce Anabel; Vázquez Gregorio, Rafael; Anschel, David J; Fregni, Felipe

2015-01-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

Opportunities for mitigating pathogen contamination during on-farm food production.

PubMed

Doyle, Michael P; Erickson, Marilyn C

2012-01-16

Fruits, vegetables, and meat are susceptible to contamination by foodborne pathogens at many points from production through preparation in the home. This review will largely highlight approaches and progress made in the last five years to address strategies to reduce pathogen contamination in animal production but will also touch on the emerging field of preharvest produce food safety. Mitigation strategies can be divided into those that address pathogen reduction in the environment and those that target reduction/elimination of pathogen contamination in animals or plants. The former strategy has been encompassed in studies evaluating sanitation treatments of facilities as well as in numerous epidemiologic risk assessment studies (both on-farm assessments and computer simulation models) that identify management practices that impact pathogen prevalence in animals. Interventions to significantly reduce pathogen exposure via feed or water are dependent on their role as a significant contributor to pathogen contamination in the animal production system. In addition, inconsistent results obtained with interventions of dietary additives or formulation modifications (grain versus forage; inclusion of distiller's grains) on pathogen prevalence in animals have been attributed to a range of factors including target organism, grain type, level of inclusion, the animal's health or stress level, and ability to survive the gastric acidic conditions. Recent attempts to microencapsulate organic acids or bacteriophage within feed have met with only marginal improvements in reducing pathogen carriage in animals but this approach may have greater potential with other antimicrobial additives (i.e., essential oils). Bacteriophage therapy, in general, can significantly reduce pathogen carriage in animals but based on its transient nature and the potential for development of phage-resistant subpopulations, this approach should be administered to animals just prior to slaughter and preferably to animals that are suspected "super-shedders". Other promising on-farm intervention approaches have included breeding for pathogen resistance, vaccines, and dietary bacteriocins. To optimize interventions on a cost basis, studies have also determined that application of dietary interventions at specific time points in the animal's production cycle is a useful strategy to reduce pathogen carriage (e.g., probiotics to fertilized eggs and acidified feed to fattening swine). In conclusion, applicable management and intervention strategies may vary depending on the type of food under production; however, it is important to consider from a holistic view how any new intervention strategies will affect the overall production system in order to maintain a successful, efficient food production environment. Copyright © 2011 Elsevier B.V. All rights reserved.

Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials.

PubMed

2008-03-01

In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The general principles for the risk assessment of GM plants and derived food and feed are followed, as described in the EFSA guidance document of the EFSA Scientific Panel on Genetically Modified Organisms. In Section 1 the mandate, scope and general principles for risk assessment of GM plant derived food and feed are discussed. Products under consideration are food and feed derived from GM plants, such as maize, soybeans, oilseed rape and cotton, modified through the introduction of one or more genes coding for agronomic input traits like herbicide tolerance and/or insect resistance. Furthermore GM plant derived food and feed, which have been obtained through extensive genetic modifications targeted at specific alterations of metabolic pathways leading to improved nutritional and/or health characteristics, such as rice containing beta-carotene, soybeans with enhanced oleic acid content, or tomato with increased concentration of flavonoids, are considered. The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended (unexpected) differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality. Key elements of the assessment procedure are the molecular, compositional, phenotypic and agronomic analysis in order to identify similarities and differences between the GM plant and its near isogenic counterpart. The safety assessment is focussed on (i) the presence and characteristics of newly expressed proteins and other new constituents and possible changes in the level of natural constituents beyond normal variation, and on the characteristics of the GM food and feed, and (ii) the possible occurrence of unintended (unexpected) effects in GM plants due to genetic modification. In order to identify these effects a comparative phenotypic and molecular analysis of the GM plant and its near isogenic counterpart is carried out, in parallel with a targeted analysis of single specific compounds, which represent important metabolic pathways in the plant like macro and micro nutrients, known anti-nutrients and toxins. Significant differences may be indicative of the occurrence of unintended effects, which require further investigation. Section 2 provides an overview of studies performed for the safety and nutritional assessment of whole food and feed. Extensive experience has been built up in recent decades from the safety and nutritional testing in animals of irradiated foods, novel foods and fruit and vegetables. These approaches are also relevant for the safety and nutritional testing of whole GM food and feed. Many feeding trials have been reported in which GM foods like maize, potatoes, rice, soybeans and tomatoes have been fed to rats or mice for prolonged periods, and parameters such as body weight, feed consumption, blood chemistry, organ weights, histopathology etc have been measured. The food and feed under investigation were derived from GM plants with improved agronomic characteristics like herbicide tolerance and/or insect resistance. The majority of these experiments did not indicate clinical effects or histopathological abnormalities in organs or tissues of exposed animals. In some cases adverse effects were noted, which were difficult to interpret due to shortcomings in the studies. Many studies have also been carried out with feed derived from GM plants with agronomic input traits in target animal species to assess the nutritive value of the feed and their performance potential. Studies in sheep, pigs, broilers, lactating dairy cows, and fish, comparing the in vivo bioavailability of nutrients from a range of GM plants with their near isogenic counterpart and commercial varieties, showed that they were comparable with those for near isogenic non-GM lines and commercial varieties. In Section 3 toxicological in vivo, in silico, and in vitro test methods are discussed which may be applied for the safety and nutritional assessment of specific compounds present in food and feed or of whole food and feed derived from GM plants. Moreover the purpose, potential and limitations of the 90-day rodent feeding trial for the safety and nutritional testing of whole food and feed have been examined. Methods for single and repeated dose toxicity testing, reproductive and developmental toxicity testing and immunotoxicity testing, as described in OECD guideline tests for single well-defined chemicals are discussed and considered to be adequate for the safety testing of single substances including new products in GM food and feed. Various in silico and in vitro methods may contribute to the safety assessment of GM plant derived food and feed and components thereof, like (i) in silico searches for sequence homology and/or structural similarity of novel proteins or their degradation products to known toxic or allergenic proteins, (ii) simulated gastric and intestinal fluids in order to study the digestive stability of newly expressed proteins and in vitro systems for analysis of the stability of the novel protein under heat or other processing conditions, and (iii) in vitro genotoxicity test methods that screen for point mutations, chromosomal aberrations and DNA damage/repair. The current performance of the safety assessment of whole foods is mainly based on the protocols for low-molecular-weight chemicals such as pharmaceuticals, industrial chemicals, pesticides, food additives and contaminants. However without adaptation, these protocols have limitations for testing of whole food and feed. This primarily results from the fact that defined single substances can be dosed to laboratory animals at very large multiples of the expected human exposure, thus giving a large margin of safety. In contrast foodstuffs are bulky, lead to satiation and can only be included in the diet at much lower multiples of expected human intakes. When testing whole foods, the possible highest concentration of the GM food and feed in the laboratory animal diet may be limited because of nutritional imbalance of the diet, or by the presence of compounds with a known toxicological profile. The aim of the 90-days rodent feeding study with the whole GM food and feed is to assess potential unintended effects of toxicological and/or nutritional relevance and to establish whether the GM food and feed is as safe and nutritious as its traditional comparator rather than determining qualitative and quantitative intrinsic toxicity of defined food constituents. The design of the study should be adapted from the OECD 90-day rodent toxicity study. The precise study design has to take into account the nature of the food and feed and the characteristics of the new trait(s) and their intended role in the GM food and feed. A 90-day animal feeding trial has a large capacity (sensitivity and specificity) to detect potential toxicological effects of single well defined compounds. This can be concluded from data reported on the toxicology of a wide range of industrial chemicals, pharmaceuticals, food substances, environmental, and agricultural chemicals. It is possible to model the sensitivity of the rat subchronic feeding study for the detection of hypothetically increased amount of compounds such as anti-nutrients, toxicants or secondary metabolites. With respect to the detection of potential unintended effects in whole GM food and feed, it is unlikely that substances present in small amounts and with a low toxic potential will result in any observable (unintended) effects in a 90-day rodent feeding study, as they would be below the no-observed-effect-level and thus of unlikely impact to human health at normal intake levels. Laboratory animal feeding studies of 90-days duration appear to be sufficient to pick up adverse effects of diverse compounds that would also give adverse effects after chronic exposure. This conclusion is based on literature data from studies investigating whether toxicological effects are adequately identified in 3-month subchronic studies in rodents, by comparing findings at 3 and 24 months for a range of different chemicals. The 90-day rodent feeding study is not designed to detect effects on reproduction or development other than effects on adult reproductive organ weights and histopathology. Analyses of available data indicate that, for a wide range of substances, reproductive and developmental effects are not potentially more sensitive endpoints than those examined in subchronic toxicity tests. Should there be structural alerts for reproductive/developmental effects or other indications from data available on a GM food and feed, then these tests should be considered. By relating the estimated daily intake, or theoretical maximum daily intake per capita for a given whole food (or the sum of its individual commercial constituents) to that consumed on average per rat per day in the subchronic 90-day feeding study, it is possible to establish the margin of exposure (safety margin) for consumers. Results obtained from testing GM food and feed in rodents indicate that large (at least 100-fold) 'safety' margins exist between animal exposure levels without observed adverse effects and estimated human daily intake. Results of feeding studies with feed derived from GM plants with improved agronomic properties, carried out in a wide range of livestock species, are discussed. The studies did not show any biologically relevant differences in the parameters tested between control and test animals. (ABSTRACT TRUNCATED)

9 CFR 355.13 - Sanitation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation. 355.13 Section 355.13 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND...

Testing of Safety-Critical Software Embedded in an Artificial Heart

NASA Astrophysics Data System (ADS)

Cha, Sungdeok; Jeong, Sehun; Yoo, Junbeom; Kim, Young-Gab

Software is being used more frequently to control medical devices such as artificial heart or robotic surgery system. While much of software safety issues in such systems are similar to other safety-critical systems (e.g., nuclear power plants), domain-specific properties may warrant development of customized techniques to demonstrate fitness of the system on patients. In this paper, we report results of a preliminary analysis done on software controlling a Hybrid Ventricular Assist Device (H-VAD) developed by Korea Artificial Organ Centre (KAOC). It is a state-of-the-art artificial heart which completed animal testing phase. We performed software testing in in-vitro experiments and animal experiments. An abnormal behaviour, never detected during extensive in-vitro analysis and animal testing, was found.

Bovine herpesvirus 1 modified live virus vaccines for cattle reproduction: Balancing protection with undesired effects.

PubMed

Chase, Christopher C L; Fulton, Robert W; O'Toole, Donal; Gillette, Benjamin; Daly, Russell F; Perry, George; Clement, Travis

2017-07-01

Bovine herpesvirus 1 (BoHV-1) has long been associated with reproductive failure in cattle following infection of the ovary and/or fetus. Vaccination prior to breeding has been an effective approach to lessen the impact of BoHV-1 on reproduction. Prior studies in the 1980s and 1990s established the susceptibility of the ovary and particularly the corpus luteum (CL) to BoHV-1 infection. A series of studies at breeding time established that: (1) in naïve animals, the CL was the major target of BoHV-1 pathology; (2) CL lesions occurred within 4-9 days after estrus; (3) similar lesions was seen with BoHV-1 MLV vaccines; (4) ovarian lesions varied by the vaccine strain used; (5) progesterone decreased with or without CL lesions; and (6) following reactivation of BoHV-1 latent infection, ovaries could become reinfected in the face of BoHV-1 immunity. Large scale field studies demonstrated that conception was highest in animals previously vaccinated and boostered with inactivated vaccine compared to animals revaccinated with MLV. In the early 2000s, to get a label claim to vaccinate calves nursing pregnant cows, safety study outlines were approved by USDA-APHIS CVB. These studies were designed to determine the effect of revaccination with MLV during pregnancy on previously vaccinated cows and were not rigorous enough to confirm complete fetal safety. As designed these studies showed no difference in reproductive loss between the previously vaccinated animals and the animals revaccinated ∼4, 7 and 9 months later, leading to the label approval for MLV vaccination in pregnant cows. Subsequent investigations by diagnostic laboratories found an increase in BoHV-1 reproductive loss after the approval for use in pregnant animals. A method was developed to differentiate IBR vaccine strains from field strains. Analysis of viruses from 31 cases from 2009-2016 indicated that all 31 isolates matched with vaccine strains. Going forward, it will be necessary to develop vaccine approaches that use non-abortifacient, nonlatent BoHV-1 vaccines that develop lifelong immunity, protecting the animal while doing no harm to the fetus. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementing a probabilistic definition of freedom from infection to facilitate trade of livestock: putting theory into praxis for the example of bovine herpes virus-1.

PubMed

Schuppers, M E; Stegeman, J A; Kramps, J A; Stärk, K D C

2012-07-01

International trade of livestock and livestock products poses a significant potential threat for spread of diseases, and importing countries therefore often require that imported animals and products are free from certain pathogens. However, absolute freedom from infection cannot be documented, since all test protocols are imperfect and can lead to false-negative results. It is possible instead to estimate the "probability of freedom from infection" and its opposite, the probability of infection despite having a negative test result. These probabilities can be estimated based on a pre-defined target prevalence, known surveillance efforts in the target population and known test characteristics of any pre-export test. Here, calculations are demonstrated using the example of bovine herpes virus-1 (BoHV-1). In a population that recently became free of BoHV-1 without using vaccination, the probability of being infected of an animal randomly selected for trade is 800 per 1 million and this probability is reduced to 64 (95% probability interval PI 6-161) per 1 million when this animal is tested negatively prior to export with a gB-ELISA. In a population that recently became free of BoHV-1 using vaccination, the probability of being infected of an animal randomly selected for trade is 200 per 1 million, and this probability can be reduced to 63 (95% PI 42-87) when this animal is tested negatively prior to export with a gE-ELISA. Similar estimations can be made on a herd level when assumptions are made about the herd size and the intensity of the surveillance efforts. Subsequently, the overall probability for an importing country of importing at least 1 infected animal can be assessed by taking into account the trade volume. Definition of the acceptable level of risk, including the probability of false-negative results to occur, is part of risk management. Internationally harmonized target prevalence levels for the declaration of freedom from infection from selected pathogens provide a significant contribution to the facilitation of international trade of livestock and livestock products by allowing exporting countries to design tailor-made output-based surveillance programs, while providing equivalent guarantees regarding the probability of freedom from infection of the population. Combining this with an approach to assess the overall probability of introducing at least 1 infected animal into an importing country during a defined time interval will help importing countries to achieve their desired level of acceptable risk and will help to assess the equivalence of animal health and food safety standards between trading partners. Copyright © 2011 Elsevier B.V. All rights reserved.

9 CFR 381.109 - Form of official poultry inspection certificate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Form of official poultry inspection certificate. 381.109 Section 381.109 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE.... Department of Agriculture Animal and Plant Health Inspection Service Meat and Poultry Inspection Program...

9 CFR 381.75 - Poultry used for research.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Poultry used for research. 381.75 Section 381.75 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Inspection Service, or the Veterinary Biologics unit of Veterinary Services, Animal and Plant Health...

9 CFR 381.75 - Poultry used for research.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Poultry used for research. 381.75 Section 381.75 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Inspection Service, or the Veterinary Biologics unit of Veterinary Services, Animal and Plant Health...

9 CFR 352.10 - Ante-mortem inspection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... to loading on the transport vehicle. (7) The transport of intact exotic animal carcasses to an... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Ante-mortem inspection. 352.10 Section 352.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

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

PubMed

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.

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

PubMed Central

Burden, Natalie; Sewell, Fiona; Chapman, Kathryn

2015-01-01

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

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

PubMed

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

2012-01-01

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

Animal models for microbicide safety and efficacy testing.

PubMed

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.

Effect of target animacy on hand preference in Sichuan snub-nosed monkeys (Rhinopithecus roxellana).

PubMed

Zhao, Dapeng; Tian, Xiangling; Liu, Xinchen; Chen, Zhuoyue; Li, Baoguo

2016-09-01

Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group-level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species.

Cypermethrin induced toxicities in fish and adverse health outcomes: Its prevention and control measure adaptation.

PubMed

Ullah, Sana; Zuberi, Amina; Alagawany, Mahmoud; Farag, Mayada Ragab; Dadar, Maryam; Karthik, Kumaragurubaran; Tiwari, Ruchi; Dhama, Kuldeep; Iqbal, Hafiz M N

2018-01-15

Pesticides are being widely employed in the modern agriculture, though in different quantities, across the globe. Although it is useful for crops yield enhancement, however, there are the serious environment, health and safety related concerns for aquatic and terrestrial living biomes that include humans, animals, and plants. Various in practice and emerging pesticides adversely affect the survival, development and biological systems stability. Several research efforts have been made to highlight the bio-safety and toxicological features of toxicants through risk assessment studies using different animal models, e.g., different fish species. Among several pesticides, cypermethrin is extensively used in agriculture and households, and the reported concentrations of this pesticide in different water bodies including rivers and streams, soil and even in rainwater are threatening. Consequently, cypermethrin is considered for risk assessment studies to know about its deep and different level of toxicological effects subject to its dose, exposure time and route. The cypermethrin existence/persistence in the environment is posing a severe threat to humans as well as another non-target terrestrial and aquatic organism. Herein, the toxic effects of pesticides, with special reference to cypermethrin, on fish, the mode of toxicity, concerns regarding public health and harmful impacts on human beings are comprehensively reviewed. The information is also given on their appropriate control and prevention strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

9 CFR 354.3 - Administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Administration. 354.3 Section 354.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... provisions of the regulations to permit experimentation so that new procedures, equipment, and processing...

9 CFR 301.1 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false General. 301.1 Section 301.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 319.305 - Tamales.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tamales. 319.305 Section 319.305 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY...

9 CFR 319.280 - Scrapple.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Scrapple. 319.280 Section 319.280 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Meat Specialties, Puddings and Nonspecific...

9 CFR 319.305 - Tamales.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Tamales. 319.305 Section 319.305 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY...

9 CFR 319.280 - Scrapple.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scrapple. 319.280 Section 319.280 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Meat Specialties, Puddings and Nonspecific...

9 CFR 416.17 - Agency verification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Agency verification. 416.17 Section 416.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... (d) Direct observation or testing to assess the sanitary conditions in the establishment. ...

9 CFR 416.17 - Agency verification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Agency verification. 416.17 Section 416.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... (d) Direct observation or testing to assess the sanitary conditions in the establishment. ...

9 CFR 416.17 - Agency verification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Agency verification. 416.17 Section 416.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... (d) Direct observation or testing to assess the sanitary conditions in the establishment. ...

9 CFR 416.17 - Agency verification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Agency verification. 416.17 Section 416.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... (d) Direct observation or testing to assess the sanitary conditions in the establishment. ...

9 CFR 416.17 - Agency verification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Agency verification. 416.17 Section 416.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... (d) Direct observation or testing to assess the sanitary conditions in the establishment. ...

9 CFR 301.1 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false General. 301.1 Section 301.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

9 CFR 306.5 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Appeals. 306.5 Section 306.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

9 CFR 439.60 - Notification and hearings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Notification and hearings. 439.60 Section 439.60 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... effect until final determination of the matter by the Administrator. ...

9 CFR 351.21 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Appeals. 351.21 Section 351.21 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

9 CFR 381.91 - Contamination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Contamination. 381.91 Section 381.91 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.89 - Bruises.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Bruises. 381.89 Section 381.89 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.92 - Overscald.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Overscald. 381.92 Section 381.92 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.93 - Decomposition.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Decomposition. 381.93 Section 381.93 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.87 - Tumors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tumors. 381.87 Section 381.87 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.88 - Parasites.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Parasites. 381.88 Section 381.88 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.84 - Airsacculitis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Airsacculitis. 381.84 Section 381.84 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.90 - Cadavers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Cadavers. 381.90 Section 381.90 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.302 - Thermal processing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Thermal processing. 381.302 Section 381.302 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... and critical factors. (2) Letters or other written communications from a processing authority...

9 CFR 355.8 - Official number.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Official number. 355.8 Section 355.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND...

9 CFR 355.36 - Obsolete labels.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Obsolete labels. 355.36 Section 355.36 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND...

9 CFR 355.8 - Official number.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Official number. 355.8 Section 355.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND...

9 CFR 355.36 - Obsolete labels.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Obsolete labels. 355.36 Section 355.36 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND...

9 CFR 320.1 - Records required to be kept.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Records required to be kept. 320.1 Section 320.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... carcasses, of any such animals, for use as human food or animal food; (2) Any person that engages in the...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

77 FR 75186 - Notice of Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT AGENCY: Bureau of... Lake Mountains in Utah County, Utah, to recreational target shooting to protect public safety. This... shooting closure within the described area will remain in effect no longer than two years from December 19...

Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception.

PubMed

Jain, Ashish; Kumar, Lokesh; Kushwaha, Bhavana; Sharma, Monika; Pandey, Aastha; Verma, Vikas; Sharma, Vikas; Singh, Vishal; Rawat, Tara; Sharma, Vishnu L; Maikhuri, Jagdamba P; Gupta, Gopal

2014-02-01

Can a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception? A 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations. Broad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro. A comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents. On/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits. A 0.003% drug 'combination' containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in ∼30 s and eliminated 100% T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The 'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5% 'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers. The number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee. Anti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health. The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

Application of real-time PCR (qPCR) for characterization of microbial populations and type of milk in dairy food products.

PubMed

Agrimonti, Caterina; Bottari, Benedetta; Sardaro, Maria Luisa Savo; Marmiroli, Nelson

2017-09-08

Dairy foods represent an important sector of the food market for their nutritional qualities and their organoleptic characteristics, which are often linked to tradition and to region. These products are typically protected by labels such as PDO (Protected Designation of Origin) and PGI (Protected Geographical Indication). Real-time PCR (qPCR) is a fundamental tool in "Food Genomics;" a discipline concerned with the residual DNA in food, which, alongside traditional physical and chemical methods, is frequently used to determine product safety, quality and authenticity. Compared to conventional or "end-point" PCR, qPCR incorporates continuous monitoring of reaction progress, thereby enabling quantification of target DNA. This review describes qPCR applications to the analysis of microbiota, and to the identification of the animal species source of milk from which dairy products have been made. These are important aspects for ensuring safety and authenticity. The various applications of qPCR are discussed, as well as advantages and disadvantages in comparison with other analytical methods.

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

PubMed

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.

Risk of Escherichia coli O157:H7, Non-O157 Shiga Toxin-Producing Escherichia coli, and Campylobacter spp. in Food Animals and Their Products in Qatar.

PubMed

Mohammed, Hussni O; Stipetic, Korana; Salem, Ahmed; McDonough, Patrick; Chang, Yung Fu; Sultan, Ali

2015-10-01

Escherichia coli O157:H7, non-O157 E. coli, and Campylobacter spp. are among the top-ranked pathogens that threaten the safety of food supply systems around the world. The associated risks and predisposing factors were investigated in a dynamic animal population using a repeat-cross-sectional study design. Animal and environmental samples were collected from dairy and camel farms, chicken processing plants, and abattoirs and analyzed for the presence of these pathogens using a combination of bacterial enrichment and real-time PCR tests without culture confirmation. Data on putative risk factors were also collected and analyzed. E. coli O157:H7 was detected by PCR at higher levels in sheep and camel feces than in cattle feces (odds ratios [OR], 6.8 and 21.1, respectively). Although the genes indicating E. coli O157:H7 were detected at a relatively higher rate (4.3%) in fecal samples from dairy cattle, they were less common in milk and udder swabs from the same animals (1 and 2%, respectively). Among the food adulterants, E. coli O103 was more common in cattle fecal samples, whereas O26 was more common in sheep feces and O45 in camel feces compared with cattle (OR, 2.6 and 3.1, respectively). The occurrence of E. coli in the targeted populations differed by the type of sample and season of the year. Campylobacter jejuni and Campylobacter coli were more common in sheep and camel feces than in cattle feces. Most of the survey and surveillance of E. coli focused on serogroup O157 as a potential foodborne hazard; however, based on the PCR results, non-O157 Shiga toxin-producing E. coli serotypes appeared to be more common, and efforts should be made to include them in food safety programs.

Assessment of the safety of aquatic animal commodities for international trade: the OIE Aquatic Animal Health code.

PubMed

Oidtmann, B; Johnston, C; Klotins, K; Mylrea, G; Van, P T; Cabot, S; Martin, P Rosado; Ababouch, L; Berthe, F

2013-02-01

Trading of aquatic animals and aquatic animal products has become increasingly globalized during the last couple of decades. This commodity trade has increased the risk for the spread of aquatic animal pathogens. The World Organisation for Animal Health (OIE) is recognized as the international standard-setting organization for measures relating to international trade in animals and animal products. In this role, OIE has developed the Aquatic Animal Health Code, which provides health measures to be used by competent authorities of importing and exporting countries to avoid the transfer of agents pathogenic for animals or humans, whilst avoiding unjustified sanitary barriers. An OIE ad hoc group developed criteria for assessing the safety of aquatic animals or aquatic animal products for any purpose from a country, zone or compartment not declared free from a given disease 'X'. The criteria were based on the absence of the pathogenic agent in the traded commodity or inactivation of the pathogenic agent by the commercial processing used to produce the commodity. The group also developed criteria to assess the safety of aquatic animals or aquatic animal products for retail trade for human consumption from potentially infected areas. Such commodities were assessed considering the form and presentation of the product, the expected volume of waste tissues generated by the consumer and the likely presence of viable pathogenic agent in the waste. The ad hoc group applied the criteria to commodities listed in the individual disease chapters of the Aquatic Animal Health Code (2008 edition). Revised lists of commodities for which no additional measures should be required by the importing countries regardless of the status for disease X of the exporting country were developed and adopted by the OIE World Assembly of Delegates in May 2011. The rationale of the criteria and their application will be explained and demonstrated using examples. © 2012 Crown Copyright. Reproduced with the permission of the Controller of Her Majesty’s Stationery Office and Cefas, Aquatic Animal Disease Group.

Accumulation patterns of lipophilic organic contaminants in surface sediments and in economic important mussel and fish species from Jakarta Bay, Indonesia.

PubMed

Dwiyitno; Dsikowitzky, Larissa; Nordhaus, Inga; Andarwulan, Nuri; Irianto, Hari Eko; Lioe, Hanifah Nuryani; Ariyani, Farida; Kleinertz, Sonja; Schwarzbauer, Jan

2016-09-30

Non-target screening analyses were conducted in order to identify a wide range of organic contaminants in sediment and animal tissue samples from Jakarta Bay. High concentrations of di-iso-propylnaphthalenes (DIPNs), linear alkylbenzenes (LABs) and polycyclic aromatic hydrocarbons (PAHs) were detected in all samples, whereas phenylmethoxynaphthalene (PMN), DDT and DDT metabolites (DDX) were detected at lower concentrations. In order to evaluate the uptake and accumulation by economic important mussel (Perna viridis) and fish species, contaminant patterns of DIPNs, LABs and PAHs in different compartments were compared. Different patterns of these contaminant groups were found in sediment and animal tissue samples, suggesting compound-specific accumulation and metabolism processes. Significantly higher concentrations of these three contaminant groups in mussel tissue as compared to fish tissue from Jakarta Bay were found. Because P. viridis is an important aquaculture species in Asia, this result is relevant for food safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Applications and safety considerations of Lactobacillus salivarius as a probiotic in animal and human health.

PubMed

Chaves, B D; Brashears, M M; Nightingale, K K

2017-03-03

The goals of this review are to summarize the current knowledge on the application of Lactobacillus salivarius as a probiotic in animals and humans, and to address safety concerns with its use on live hosts. Overall, several strains of L. salivarius are well established probiotics with multiple applications in animal health, particularly to reduce colonization by gastrointestinal pathogens, and to a lesser extent, as a production and quality aid. In humans, L. salivarius has been used to prevent and treat a variety of chronic diseases, including asthma, cancer, atopic dermatitis and halitosis, and to a much limited extent, to prevent or treat infections. Based on the results from primary research evidence, it seems that L. salivarius does not pose a health risk to animals or humans in the doses currently used for a variety of applications; however, there is a systematic lack of studies assuring the safety of many of the strains intended for clinical use. This review provides researchers in the field with up-to-date information regarding applications and safety of L. salivarius. Furthermore, it helps researchers identify knowledge gaps and potential opportunities for microbiological and clinical research. © 2017 The Society for Applied Microbiology.

9 CFR 590.10 - Authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Authority. 590.10 Section 590.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... permit experimentation so that new procedures, equipment, and processing techniques may be tested to...

9 CFR 590.10 - Authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Authority. 590.10 Section 590.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... permit experimentation so that new procedures, equipment, and processing techniques may be tested to...

9 CFR 590.10 - Authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Authority. 590.10 Section 590.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... permit experimentation so that new procedures, equipment, and processing techniques may be tested to...

9 CFR 590.10 - Authority.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Authority. 590.10 Section 590.10 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... permit experimentation so that new procedures, equipment, and processing techniques may be tested to...

9 CFR 304.1 - Application for inspection.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Application for inspection. 304.1 Section 304.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...

9 CFR 354.245 - Vermin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Vermin. 354.245 Section 354.245 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Precautions Against Contamination of Products § 354.245 Vermin. Every practicable precaution shall be taken to...

9 CFR 381.84 - Airsacculitis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Airsacculitis. 381.84 Section 381.84 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... carcasses may be passed for food after complete removal and condemnation of all affected tissues including...

9 CFR 381.84 - Airsacculitis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Airsacculitis. 381.84 Section 381.84 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... carcasses may be passed for food after complete removal and condemnation of all affected tissues including...

9 CFR 381.84 - Airsacculitis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Airsacculitis. 381.84 Section 381.84 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... carcasses may be passed for food after complete removal and condemnation of all affected tissues including...

9 CFR 381.84 - Airsacculitis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Airsacculitis. 381.84 Section 381.84 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... carcasses may be passed for food after complete removal and condemnation of all affected tissues including...

9 CFR 417.7 - Training.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Training. 417.7 Section 417.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY REQUIREMENTS UNDER THE FEDERAL MEAT INSPECTION ACT AND THE POULTRY PRODUCTS INSPECTION ACT HAZARD ANALYSIS AND...

9 CFR 417.7 - Training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Training. 417.7 Section 417.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY REQUIREMENTS UNDER THE FEDERAL MEAT INSPECTION ACT AND THE POULTRY PRODUCTS INSPECTION ACT HAZARD ANALYSIS AND...

9 CFR 417.7 - Training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Training. 417.7 Section 417.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY REQUIREMENTS UNDER THE FEDERAL MEAT INSPECTION ACT AND THE POULTRY PRODUCTS INSPECTION ACT HAZARD ANALYSIS AND...

9 CFR 417.7 - Training.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Training. 417.7 Section 417.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY REQUIREMENTS UNDER THE FEDERAL MEAT INSPECTION ACT AND THE POULTRY PRODUCTS INSPECTION ACT HAZARD ANALYSIS AND...

9 CFR 417.7 - Training.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Training. 417.7 Section 417.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE REGULATORY REQUIREMENTS UNDER THE FEDERAL MEAT INSPECTION ACT AND THE POULTRY PRODUCTS INSPECTION ACT HAZARD ANALYSIS AND...

9 CFR 319.302 - Hash.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Hash. 319.302 Section 319.302 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION...

9 CFR 319.600 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false [Reserved] 319.600 Section 319.600 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Meat Snacks, Hors d'Oeuvres, Pizza, and...

9 CFR 381.166 - Breaded products.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Breaded products. 381.166 Section 381.166 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Definitions and Standards of Identity or Composition § 381...

9 CFR 319.701 - Mixed fat shortening.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Mixed fat shortening. 319.701 Section 319.701 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

9 CFR 319.701 - Mixed fat shortening.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Mixed fat shortening. 319.701 Section 319.701 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

9 CFR 381.166 - Breaded products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Breaded products. 381.166 Section 381.166 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Definitions and Standards of Identity or Composition § 381...

9 CFR 381.159 - Poultry rolls.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Poultry rolls. 381.159 Section 381.159 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Definitions and Standards of Identity or Composition § 381...

9 CFR 319.600 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false [Reserved] 319.600 Section 319.600 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Meat Snacks, Hors d'Oeuvres, Pizza, and...

9 CFR 319.302 - Hash.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Hash. 319.302 Section 319.302 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION...

9 CFR 381.159 - Poultry rolls.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Poultry rolls. 381.159 Section 381.159 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Definitions and Standards of Identity or Composition § 381...

9 CFR 302.1 - Establishments requiring inspection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Establishments requiring inspection. 302.1 Section 302.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...

9 CFR 592.370 - Certificate issuance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Certificate issuance. 592.370 Section 592.370 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.370...

9 CFR 592.80 - Political activity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Political activity. 592.80 Section 592.80 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Performance of Services § 592.80 Political...

9 CFR 592.600 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false General. 592.600 Section 592.600 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Sanitary and Processing Requirements § 592.600 General...

9 CFR 592.460 - Appeal certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Appeal certificates. 592.460 Section 592.460 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Appeals § 592.460 Appeal certificates. Immediately...

9 CFR 592.70 - Identification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Identification. 592.70 Section 592.70 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Performance of Services § 592.70 Identification. All...

9 CFR 592.360 - Certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Certificates. 592.360 Section 592.360 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.360 Certificates...

9 CFR 351.2 - Terms defined.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Terms defined. 351.2 Section 351.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

9 CFR 351.18 - Official identifications; unauthorized use.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Official identifications; unauthorized use. 351.18 Section 351.18 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION...