RESUMEN
Representatives of applied science (e.g. governmental organizations, academia, and industry) met to discuss the progress towards a harmonized human health risk assessment in developmental toxicology of plant protection products, biocidal products, and other environmental chemicals at the 9th Berlin Workshop on Developmental Toxicity held in September 2018. Within the focus of the scientific discussion were the future of in-vitro methods for developmental and reproductive toxicology, the potential relevance of alternative species in testing of developmental effects, and risk and hazard assessment of developmental and endocrine effects. Furthermore, the need for a harmonized terminology for classification of anomalies in laboratory animals in developmental toxicity studies aiming for human health risk assessment was determined. Here, the DevTox database was identified as an extremely valuable tool. Overall, the participants agreed that still one of the biggest challenges for testing developmental toxicity in the 21st century is the development of animal-free test strategies and alternatives to animal testing that could provide human-relevant information in a rapid, efficient, and mechanistically informative manner.
Asunto(s)
Alternativas al Uso de Animales/métodos , Bases de Datos Factuales/tendencias , Reproducción/efectos de los fármacos , Toxicología/métodos , Alternativas al Uso de Animales/tendencias , Animales , Berlin , Medición de Riesgo , Especificidad de la Especie , Terminología como Asunto , Toxicología/tendenciasRESUMEN
The recent Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on "The need for nonhuman primates in biomedical research, production and testing of products and devices" (2017 SCHEER) highlights approaches that could significantly contribute to the replacement, reduction, and refinement of nonhuman primate (NHP) studies. Initiatives that have the potential to affect NHP welfare and/or their use are expected to be appropriate, fair, and objective and publicly disseminated information focused on NHPs in biomedical research, which includes toxicologic and pathologic research and testing, should be objectively evaluated by stakeholder scientists, researchers, and veterinarians. Thus, IQ Consortium member companies convened to develop an informed and objective response, focusing on identifying areas of agreement, potential gaps, or missing information in 2017 SCHEER. Overall, the authors agree that many positions in the 2017 SCHEER Opinion generally align with industry views on the use of NHPs in research and testing, including the ongoing need of NHPs in many areas of research. From the perspective of the IQ Consortium, there are several topics in the 2017 SCHEER that merit additional comment, attention, or research, as well as consideration in future opinions.
Asunto(s)
Alternativas al Uso de Animales/tendencias , Investigación Biomédica/métodos , Evaluación Preclínica de Medicamentos/tendencias , Primates , Alternativas al Uso de Animales/ética , Alternativas al Uso de Animales/legislación & jurisprudencia , Bienestar del Animal , Animales , Bioética , Investigación Biomédica/ética , Investigación Biomédica/legislación & jurisprudencia , Evaluación Preclínica de Medicamentos/ética , Evaluación Preclínica de Medicamentos/métodos , Unión Europea , Regulación GubernamentalAsunto(s)
Academias e Institutos/organización & administración , Alternativas al Uso de Animales/tendencias , Animales de Laboratorio , Genómica , Vivienda para Animales/organización & administración , Animales , Línea Celular , Modelos Animales de Enfermedad , Ratones , Organoides , Ratas , Reino Unido , Xenopus , Pez CebraRESUMEN
Research endeavors aiming to understand the maternal immune adaptation to pregnancy significantly rely on the use of animal models, such as mice and rats. These models have provided important insights into the pathophysiology of a number of pregnancy disorders in humans. However, the use of animal models in scientific research is a vividly debated and emotive topic. The 3R principles - replacement, reduction and refinement of research animals - have been propagated a few decades ago. The present review advocates a forward-thinking consciousness to address the 3R principles in research projects in the field of reproductive biology and immunology. Specific measures and alternative methods are being proposed to replace research animals by using e.g. tissue engineering approaches, biobank-derived tissue, 'placenta-on-a-chip' devices or in silico methods. The latter may involve data queries from repositories now available to provide single cell sequencing information on reproductive tissues. Reduction of research animals by gestational imaging and a wealth of suggestions for refinement are proposed. Taken together, the measures and guidelines introduced in this review are expected to spark a reconsideration of experimental designs in the area of reproductive biology and immunology in order to implement 3R principle where applicable.
Asunto(s)
Alternativas al Uso de Animales/métodos , Reproducción/inmunología , Proyectos de Investigación/normas , Alternativas al Uso de Animales/tendencias , Animales , Simulación por Computador , Femenino , Guías como Asunto , Ratones , Modelos AnimalesRESUMEN
In vitro chemical safety testing methods offer the potential for efficient and economical tools to provide relevant assessments of human health risk. To realize this potential, methods are needed to relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available IVIVE approaches need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency Office of Research and Development and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop and webinar series. Here, we integrate content from the webinars and workshop to discuss activities and resources that would promote inclusion of IVIVE in regulatory decision-making. We discuss properties of models that successfully generate predictions of in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making.
Asunto(s)
Seguridad Química/métodos , Toma de Decisiones Asistida por Computador , Toma de Decisiones en la Organización , Prioridades en Salud , Ensayos Analíticos de Alto Rendimiento , Modelos Biológicos , Pruebas de Toxicidad/métodos , Alternativas al Uso de Animales/tendencias , Animales , Seguridad Química/instrumentación , Seguridad Química/legislación & jurisprudencia , Seguridad Química/tendencias , Biología Computacional , Simulación por Computador , Sistemas Especialistas , Guías como Asunto , Prioridades en Salud/tendencias , Ensayos Analíticos de Alto Rendimiento/tendencias , Humanos , National Institute of Environmental Health Sciences (U.S.) , Pruebas de Toxicidad/instrumentación , Pruebas de Toxicidad/tendencias , Estados Unidos , United States Dept. of Health and Human Services , United States Environmental Protection AgencyRESUMEN
The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review. In this review, focused on human lung epithelial cell cultures as a model for inhalation toxicology, we discuss the choice of cells for these models, the cell culture system used, the method of exposure as well as the various read-outs to assess the cellular response. We argue that rapid developments in the 3D culture of primary epithelial cells, the use of induced pluripotent stem cells for generation of lung epithelial cells and the development of organ-on-a-chip technology are among the important developments that will allow significant advances in this field. Furthermore, we discuss the various routes of application of inhaled toxicants by air-liquid interface models as well as the vast array of read-outs that may provide essential information. We conclude that close collaboration between researchers from various disciplines is essential for development of valid methods that are suitable for replacement of animal studies for inhalation toxicology.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Drogas en Investigación/efectos adversos , Dispositivos Laboratorio en un Chip , Pulmón/efectos de los fármacos , Mucosa Respiratoria/efectos de los fármacos , Pruebas de Toxicidad/métodos , Administración por Inhalación , Aerosoles , Alternativas al Uso de Animales/tendencias , Cámaras de Exposición Atmosférica/tendencias , Línea Celular , Células Cultivadas , Drogas en Investigación/administración & dosificación , Guías como Asunto , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Dispositivos Laboratorio en un Chip/tendencias , Pulmón/citología , Pulmón/fisiología , Microfluídica/tendencias , Reproducibilidad de los Resultados , Mucosa Respiratoria/citología , Mucosa Respiratoria/fisiología , Ingeniería de Tejidos/tendencias , Pruebas de Toxicidad/instrumentación , Pruebas de Toxicidad/normas , Pruebas de Toxicidad/tendenciasRESUMEN
Since the inception of the Association of American Veterinary Medical Colleges (AAVMC), the use of animals in research and education has been a central element of the programs of member institutions. As veterinary education and research programs have evolved over the past 50 years, so too have societal views and regulatory policies. AAVMC member institutions have continually responded to these events by exchanging best practices in training their students in the framework of comparative medicine and the needs of society. Animals provide students and faculty with the tools to learn the fundamental knowledge and skills of veterinary medicine and scientific discovery. The study of animal models has contributed extensively to medicine, veterinary medicine, and basic sciences as these disciplines seek to understand life processes. Changing societal views over the past 50 years have provided active examination and continued refinement of the use of animals in veterinary medical education and research. The future use of animals to educate and train veterinarians will likely continue to evolve as technological advances are applied to experimental design and educational systems. Natural animal models of both human and animal health will undoubtedly continue to serve a significant role in the education of veterinarians and in the development of new treatments of animal and human disease. As it looks to the future, the AAVMC as an organization will need to continue to support and promote best practices in the humane care and appropriate use of animals in both education and research.
Asunto(s)
Animales de Laboratorio , Educación en Veterinaria/historia , Modelos Animales , Experimentación Animal/historia , Experimentación Animal/legislación & jurisprudencia , Alternativas al Uso de Animales/historia , Alternativas al Uso de Animales/legislación & jurisprudencia , Alternativas al Uso de Animales/tendencias , Bienestar del Animal/historia , Bienestar del Animal/legislación & jurisprudencia , Animales , Educación en Veterinaria/métodos , Educación en Veterinaria/tendencias , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Historia Antigua , Vínculo Humano-Animal , Humanos , Estados UnidosRESUMEN
Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.
Asunto(s)
Experimentación Animal/ética , Experimentación Animal/normas , Alternativas al Uso de Animales/tendencias , Modelos Animales de Enfermedad , Primates , Animales , Bioética , China , HumanosAsunto(s)
Experimentación Animal/normas , Informe de Investigación , Experimentación Animal/ética , Experimentación Animal/legislación & jurisprudencia , Alternativas al Uso de Animales/métodos , Alternativas al Uso de Animales/organización & administración , Alternativas al Uso de Animales/tendencias , Bioética , Ética en Investigación , Informe de Investigación/normas , Informe de Investigación/tendenciasRESUMEN
Scientists planning research that involves the use of animals are required by international and/or national law to examine the possibilities for the implementation of Replacement, Reduction and/or Refinement (the Three Rs principles of Russell and Burch) in experiments for research, testing, and education. There are two Korean laws legislating humane use of animals and ethical review prior to animal experiments. This report reviews current practice of the literature search by the researchers and protocol review by the Institutional Animal Care and Use Committees on the Replacement, Reduction and Refinement alternatives in Korea. The promotion and protection of the laboratory animals are one of the core competencies of investigators exploring the ethical conduct of research and good science.
Asunto(s)
Experimentación Animal/ética , Alternativas al Uso de Animales/educación , Animales de Laboratorio , Investigación/educación , Alternativas al Uso de Animales/tendencias , Animales , Humanos , República de CoreaRESUMEN
This literature review documents trends in the use of mice in prolonged pain research, defined herein as research that subjects mice to a source of pain for at least 14 days. The total amount of prolonged pain research on mice has increased dramatically in the past decade for the 3 pain categories examined: neuropathic, inflammatory, and chronic pain. There has also been a significant rise in the number of prolonged mouse pain studies as a proportion of all mouse studies and of all mouse pain studies. The use of transgenic mice has also risen significantly in prolonged pain research, though not as a proportion of all mice used in prolonged pain research. There has not been significant overall change in the number of mice being used per study for any of the 3 pain categories or for any of 3 common pain inducement models: chronic constriction injury, partial sciatic nerve ligation, and complete Freund's adjuvant. Finally, although most authors referred to approval of experiments by an institutional nonhuman animal use committee, there were no references to the "3Rs" in a random selection of 55 papers examined. Given the proportionally high volume of mice used in invasive research and the gravity of studies that inflict lasting pain, these trends raise serious questions about whether the 3Rs principles of Replacement, Reduction, and Refinement are being appropriately implemented by researchers and institutions.
Asunto(s)
Experimentación Animal/ética , Bienestar del Animal/tendencias , Modelos Animales de Enfermedad , Ratones , Dolor , Experimentación Animal/estadística & datos numéricos , Alternativas al Uso de Animales/estadística & datos numéricos , Alternativas al Uso de Animales/tendencias , Bienestar del Animal/ética , Bienestar del Animal/estadística & datos numéricos , Animales , Dolor Crónico , Inflamación , Ratones Transgénicos , NeuralgiaAsunto(s)
Experimentación Animal/legislación & jurisprudencia , Derechos del Animal/legislación & jurisprudencia , Alternativas al Uso de Animales/legislación & jurisprudencia , Bienestar del Animal/legislación & jurisprudencia , Animales de Laboratorio , Regulación Gubernamental , Experimentación Animal/ética , Alternativas al Uso de Animales/tendencias , Bienestar del Animal/ética , Animales , Agencias Gubernamentales , Humanos , Sector Privado , Apoyo a la Investigación como Asunto , Responsabilidad Social , Estados UnidosRESUMEN
Mechanistic toxicology has evolved by relying, to a large extent, on methodologies that substitute or complement traditional animal tests. The biotechnology and informatics revolutions of the last decades have made such technologies broadly available and useful, but regulatory toxicology has been slow to embrace these new approaches. Major validation efforts, however, have delivered the evidence that new approaches do not lower safety standards and can be integrated into regulatory safety assessments. Particularly in the EU, political pressures, such as the REACH legislation and the 7th Amendment to the cosmetic legislation, have prompted the need of new approaches. In the US, the NRC vision report calling for a toxicology for the 21st century (and its most recent adaptation by EPA for their toxicity testing strategy) have initiated a debate about how to create a novel approach based on human cell cultures, lower species, high-throughput testing, and modeling. Lessons learned from the development, validation, and acceptance of alternative methods support the creation of a new approach based on identified toxicity pathways. Conceptual steering and an objective assessment of current practices by evidence-based toxicology (EBT) are required. EBT is modeled on evidence-based medicine, which has demonstrated that rigorous systematic reviews of current practices and meta-analyses of studies provide powerful tools to provide health care professionals and patients with the current best scientific evidence. Similarly, a portal for high-quality reviews of toxicological approaches and tools for the quantitative meta-analyses of data promise to serve as door opener for a new regulatory toxicology.
Asunto(s)
Alternativas al Uso de Animales/tendencias , Toxicología/tendencias , Alternativas al Uso de Animales/economía , Alternativas al Uso de Animales/legislación & jurisprudencia , Alternativas al Uso de Animales/métodos , Bienestar del Animal/legislación & jurisprudencia , Animales , Cosméticos/normas , Cosméticos/toxicidad , Medicina Basada en la Evidencia , Regulación Gubernamental , Humanos , Medición de Riesgo , Pruebas de Toxicidad/economía , Pruebas de Toxicidad/métodos , Pruebas de Toxicidad/normas , Pruebas de Toxicidad/tendencias , Toxicología/economía , Toxicología/legislación & jurisprudencia , Toxicología/métodosRESUMEN
Animal models serve an important role in assessing preclinical safety and efficacy of new medicines and vaccines; however, such assessments can involve significant pain and distress and large numbers of animals. Best practice approaches seek to enhance animal well-being, minimize or avoid pain and distress, and use fewer animals. Advances in science and technology are providing opportunities for improved mechanism-based models and integrated safety assessments that will support improved animal welfare and reduce animal use.