CEBS update: curated toxicology database with enhanced tools for data integration.

The Chemical Effects in Biological Systems database (CEBS) contains extensive toxicology study results and metadata from the Division of the National Toxicology Program (NTP) and other studies of environmental health interest. This resource grants public access to search and collate data from over 10 250 studies for 12 750 test articles (chemicals, environmental agents). CEBS has made considerable strides over the last 5 years to integrate growing internal data repositories into data warehouses and data marts to better serve the public with high quality curated datasets. This effort includes harmonizing legacy terms and metadata to current standards, mapping test articles to external identifiers, and aligning terms to OBO (Open Biological and Biomedical Ontology) Foundry ontologies. The data are made available through the CEBS Homepage (https://cebs.niehs.nih.gov/cebs/), guided search applications, flat files on FTP (file transfer protocol), and APIs (application programming interface) for user access and to provide a bridge for computational tools. The user interface is intuitive with a single search bar to query keywords related to study metadata, publications, and data availability. Results are consolidated to single pages for each test article with NTP conclusions, publications, individual studies, data collections, and links to related test articles and projects available together.

Laboratory animal welfare: environmental enrichment shows positive effect on animal testing / Bem-estar animal em laboratório: enriquecimento ambiental apresenta efeito positivo na experimentação animal

Reproductive and developmental toxicology has focused on the need to approach the effects of organism exposure to various drugs during pregnancy after the mid-50's, when the thalidomide tragedy stroke humanity. In recent decades, this area of study has developed a lot due to animal testing, raising awareness on the need to improve the quality of life of such animals. Therefore, this paper aims to investigate how the science of animal welfare can improve scientific research as a whole, including the reproductive and developmental toxicology fields, by emphasizing environmental enrichment in animal facilities. To do so, we conducted an integrative literature review on several quantitative and qualitative methodological approaches that are applicable to toxicology studies. Here, we present evidence that environmental enrichment improves animal welfare and prevents or reduces the negative effects of captive housing, which must be a principle of toxicological research for ethical, legal and scientific reasons.(AU)

Na toxicologia da reprodução e do desenvolvimento, a atenção necessária foi dada aos efeitos da exposição do organismo às inúmeras drogas durante o período gestacional somente após a metade dos anos 50, quando a tragédia da talidomida atingiu a humanidade. Assim, esta área alcançou desenvolvimento científico com a contribuição da experimentação animal nas últimas décadas. O uso de animais de laboratórios para a pesquisa científica expôs a necessidade de melhorar a qualidade de vida destas espécies. Portanto, este trabalho tem como objetivo investigar como a ciência do bem-estar animal pode melhorar a pesquisa científica como um todo, incluindo na área de toxicologia da reprodução e de desenvolvimento, enfatizando o enriquecimento ambiental em biotérios. Uma revisão integrativa de literatura foi realizada, incluindo abordagens quantitativas e qualitativas, quais podem ser aplicadas para estudos de toxicologia. Aqui, são mostradas evidências de que o enriquecimento ambiental melhora o bem-estar animal e previne ou reduz os efeitos negativos do cativeiro, qual deve um princípio da pesquisa toxicológica por razões éticas, argumentos legais e garantias científicas.(AU)

Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.

The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

6000 días más: evidencia neurocientífica acerca del impacto de la pobreza infantil / 6000 more days: Neuroscientific evidence about the impact of childhood poverty

El estudio neurocientífico de la pobreza infantil realizado por diferentes grupos de investigación durante las últimas dos décadas ha permitido acumular evidencia que indica que el impacto de las carencias materiales y simbólicas por pobreza, desde la concepción, puede limitar las oportunidades de desarrollo e inclusión social de las personas durante todo su ciclo vital. No obstante, la potencialidad de cambio inherente a la plasticidad neural, las diferencias individuales y las posibilidades de modificación del desarrollo autorregulatorio por intervención ambiental (i.e., familiar, escolar y comunitaria) también indican que los impactos no son iguales en todos los casos, que no hay un período crítico para el desarrollo cognitivo y las competencias de aprendizaje que se limite a los primeros 1000 días, que la irreversibilidad del impacto de la pobreza no es un fenómeno que afecte a todos los niños que la padecen y que la pobreza no implica necesariamente déficit del desarrollo

Neuroscientific study on child poverty carried out by several research groups over the last two decades has allowed us to gather evidence showing that the impact of material and symbolic needs from poverty, may from the onset limit opportunities of development and social inclusion of people throughout their life cycle. Nevertheless, the potential shift inherent to neural plasticity, individual differences, and the potential change of self-regulatory development by means of environment intervention (i.e., family, school, and community) also show that impacts are not the same for every child, that there is no critical period for cognitive development and learning competencies that is limited to the first 1,000 days, that irreversibility of poverty impact is not a fact that affects every child exposed to it, and that poverty does not necessary means developmental déficit

El Khat: usos, efectos secundarios y peligros de una planta psicoestimulante / Khat: Uses, side-effects and dangers of a psycho-stimulant plant

El Khat o Catha Edulis Forsk, es un arbusto que se emplea por sus propiedades euforizantes y estimulantes del sistema nervioso central y por su capacidad para aliviar la fatiga, sin embargo, su consumo abusivo produce efectos adversos sobre las funciones cognitivas. En este artículo de revisión se resume el origen, la producción, farmacología, toxicología, neuropsicología y los aspectos psicosociales del consumo del khat en un intento por aportar el mayor conocimiento posible sobre este arbusto, sus propiedades y efectos. Además, se centra especial atención en los aspectos psicológicos y neuropsicológicos que produce, entre los que se incluyen alteraciones leves del estado de ánimo y profundos trastornos que pueden variar tanto en intensidad como en duración. Pese a que se ha podido constatar que determinadas situaciones sociales pueden aumentar el consumo de determinadas drogas de precios asequibles, las consecuencias que producen en la sociedad hacen que sea necesaria una concienciación mayor sobre todos los aspectos que rodean su consumo. Existe un mercado legal e ilegal, con una parte de la población del cuerno de África y de la península arábiga bajo los efectos del Khat, que conlleva unas consecuencias graves para la salud

Khat (Catha edulis) is a shrub used for its euphoric and central nervous system- stimulating properties and for its ability to relieve fatigue. Its abusive consumption nevertheless produces adverse effects on cognitive functions. In this paper we provide a summarized review of the origin, production, pharmacology, toxicology, neuropsychology and psychosocial aspects of khat consumption, in an attempt to provide the best possible knowledge about the bush, its properties and effects. We also focus special attention on the psychological and neuropsychological aspects involved, including minor or major alterations of mood disorders. Although it has been shown that certain social situations can increase the consumption of certain drugs at affordable prices, the impact on several societies requires a greater awareness of all the aspects involved in its consumption. There is a legal and illegal market, with part of the population in the horn of Africa and the Arabian peninsula under the influence of Khat, with serious consequences for the health

Indicadores de calidad en la asistencia toxicológica / Quality indicators in toxicological assistance

No disponible

Thoracic and respirable particle definitions for human health risk assessment.

BACKGROUND: Particle size-selective sampling refers to the collection of particles of varying sizes that potentially reach and adversely affect specific regions of the respiratory tract. Thoracic and respirable fractions are defined as the fraction of inhaled particles capable of passing beyond the larynx and ciliated airways, respectively, during inhalation. In an attempt to afford greater protection to exposed individuals, current size-selective sampling criteria overestimate the population means of particle penetration into regions of the lower respiratory tract. The purpose of our analyses was to provide estimates of the thoracic and respirable fractions for adults and children during typical activities with both nasal and oral inhalation, that may be used in the design of experimental studies and interpretation of health effects evidence. METHODS: We estimated the fraction of inhaled particles (0.5-20 µm aerodynamic diameter) penetrating beyond the larynx (based on experimental data) and ciliated airways (based on a mathematical model) for an adult male, adult female, and a 10 yr old child during typical daily activities and breathing patterns. RESULTS: Our estimates show less penetration of coarse particulate matter into the thoracic and gas exchange regions of the respiratory tract than current size-selective criteria. Of the parameters we evaluated, particle penetration into the lower respiratory tract was most dependent on route of breathing. For typical activity levels and breathing habits, we estimated a 50% cut-size for the thoracic fraction at an aerodynamic diameter of around 3 µm in adults and 5 µm in children, whereas current ambient and occupational criteria suggest a 50% cut-size of 10 µm. CONCLUSIONS: By design, current size-selective sample criteria overestimate the mass of particles generally expected to penetrate into the lower respiratory tract to provide protection for individuals who may breathe orally. We provide estimates of thoracic and respirable fractions for a variety of breathing habits and activities that may benefit the design of experimental studies and interpretation of particle size-specific health effects.

La docencia de la Toxicología en la Universitat de Valencia ante la convergencia europea / Teaching toxicology in the University of V alencia through the European convergence

La incorporación del Espacio de Europeo de Educación Superior (EEES) al sistema de enseñanza universitario ha supuesto un cambio en las metodologías enseñanza-aprendizaje de las distintas titulaciones que comprende la Universitat de València (UV). En este artículo se realiza un repaso a la transformación que supuesto el EEES en la enseñanza de la toxicología en la UV tanto en el pregrado como en el grado. En los grados de Farmacia, Ciencias Ambientales, Ciencias y Tecnología de los Alimentos y Nutrición Humana y Dietética se han mantenido las asignaturas obligatorias que se impartían, pero además la Toxicología participa en otras asignaturas obligatorias y nuevas asignaturas optativas. Además, con los nuevos Grados se han incluido enseñanzas en Toxicología en el Grado de Medicina y Criminología. Actualmente, el área de toxicología participa en el Master oficial de Calidad y Seguridad Alimentaria y en el Doctorado en Ciencias de la Alimentación. Este aumento de la participación de la Toxicología en los nuevos Grados y postgrados responde a la demanda por parte de la sociedad de profesionales con mayores conocimientos toxicológicos (AU)

The incorporation of the European Higher Education Area (EHEA) to the university education system has meant a change in the teaching-learning methodologies of the different qualifications that are included in the Universitat de València (UV). This work takes a look at the transformation that the EHEA has brought to the teaching of toxicology in the UV, in both graduate and postgraduate degrees. In grades of Pharmacy, Environmental Sciences, Sciences and Food Technology and Human Nutrition and Dietetics have remained the core subjects that were taught, but also Toxicology participates in other core subjects and new electives ones. In addition, the Toxicology studies have been included in the Grade of Medicine and Criminology. Currently, the area of toxicology participates in the of ficial Master of Quality and Food Safety and PhD in Food Science. This increased participation of Toxicology in the new graduate degrees responds to the demand from the society of professional with more knowledge in toxicology (AU)

"ToxRTool", a new tool to assess the reliability of toxicological data.

Evaluation of the reliability of toxicological data is of key importance for regulatory decision-making. In particular, the new EU Regulations concerning the registration, evaluation, authorisation and restriction of chemicals (REACH) and classification, labelling and packaging (CLP) according to the new globally harmonised system (GHS) rely on the integration of all available toxicological information. The so-called Klimisch categories, although well established and widely used, lack detailed criteria for assigning data quality to categories. A software-based tool (ToxRTool) was developed within the context of a project funded by the European Commission to provide comprehensive criteria and guidance for reliability evaluations of toxicological data. It is applicable to various types of experimental data, endpoints and studies (study reports, peer-reviewed publications) and leads to the assignment to Klimisch categories 1, 2 or 3. The tool aims to increase transparency and to harmonise approaches of reliability assessment. The tool consists of two parts, one to evaluate in vivo and one to evaluate in vitro data. The prototypes of the tool were tested in two independent inter-rater experiments. This approach allowed the analysis of the performance of the tool in practice and the identification and minimisation of sources of heterogeneity in evaluation results. The final version, ToxRTool, is publicly available for testing and use.

Aportaciones de la Toxicología Clínica al conjunto de la investigación toxicológica en España durante 15 años (1991-2005) / Contribution of clinical toxicology to total toxicological research in Spain (1991-2005)

Cada vez resulta más importante medir de forma objetiva la producción científica individual, de los grupos de investigación o de un área científica, para lo que se utilizan parámetros bibliométricos. En el presente estudio se analiza la actividad investigadora llevada a cabo por los toxicólogos españoles durante 15años, se compara con la de otras áreas científicas y con la de los toxicólogos de otros países y, finalmente, se investiga la aportación de la toxicología clínica al conjunto de la investigación toxicológica española. Se empleó como herramienta de búsqueda bibliométrica de documentos científicos publicados por toxicólogos españoles el programa Web of Knowledge del Institute for Science Information(ISI) y como base de datos el Science Citation Index (SCI). El periodo de tiempo analizado fue de 1991 a 2005. Los datos tabulados fueron: año de publicación, nombre de la revista y su factor de impacto, país del editor de la revista, tipo e idioma del documento, centro, provincia y comunidad del primer toxicólogo firmante, colaboración con otros servicios de toxicología y número de citas que recibió el artículo. Para el análisis estadístico, los datos se introdujeron en el programa informático SPSS versión 12.0. Durante los 15 años estudiados se han identificado 1904 documentos firmados por toxicólogos españoles y publicados en 523 revistas diferentes. Durante este periodo de tiempo, se ha observado un incremento progresivo y significativo del número de documentos firmados por toxicólogos, así como de los documentos encuadrados en el área de toxicología. Sin embargo, como la producción científica global en España ha mostrado un marcado aumento, el porcentaje que supone la toxicología respecto a la producción total española, ha experimentado un significativo descenso. En un 16% de los trabajos se estableció una colaboración internacional...(AU)

Objective measurement of scientific production by individuals, research groups or scientific areas using bibliometric parameters is increasingly important. The aims of this study were to analyze the research made by spanish toxicologists during a 15-year period, to compare it with that of other scientific areas and toxicologists from other countries and to determine the contribution of clinical toxicology to total spanish toxicological lresearch. The Web of Knowledge programme of the Institute for Science Information (ISI) and the Science Citation Index (SCI) database were used to carry out a bibliometric search for scientific documents published by spanish toxicologists from 1991 to 2005.The data tabulated were: year of publication, names of the journal and its impact factor, nationality of the journal's editor, type and language of the document, centre, province and community of the first toxicologist author, collaboration with other toxicology services and number of citations of each article. The statistical analysis was made using the SPSS version 12.0 statistical programme. During the study period, 1904 works authored by spanish toxicologists appearing in523 different journals were identified. There was a significant, progressive increase in the number of works authored by toxicologists and the number of works in the area of toxicology during the study period. However, as global scientific production in Spain increased markedly during this period, the percentage of toxicological works as a percentage of total spanish scientific production fell significantly. There was international collaboration in16% of the toxicological studies included. A total of 79 spanish toxicological centres authored scientific works, with the greatest number being produced by the autonomic communities of Catalonia, Andalusia and Madrid...(AU)

Medical devices; clinical chemistry and clinical toxicology devices; drug metabolizing enzyme genotyping system. Final rule.

The Food and Drug Administration (FDA) is classifying drug metabolizing enzyme (DME) genotyping test systems into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping System." The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Medical devices; clinical chemistry and clinical toxicology devices; instrumentation for clinical multiplex test systems. Final rule.

The Food and Drug Administration (FDA) is classifying instrumentation for clinical multiplex test systems into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems." The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Medical devices; clinical chemistry and clinical toxicology devices; classification of newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. Final rule.

The Food and Drug Administration (FDA) is classifying newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, the Food and Drug Administration Modernization Act of 1997, and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Análisis de la producción científica en Revista de Toxicologia: período 1983-2000 / Analysis of the scientific production in 'Revista de Toxicologia': years 1983 to 2000

Se analizan de forma breve aspectos de la producción científica aparecida en la Revista de Toxicología en un período de 18 años (1983-2000). Se elaboró una ficha de cada una de las publicaciones de la revista y los trabajos se catalogaron por secciones: Toxicología experimental, Métodos analíticos, Toxicología clínica, Toxicología ambiental, etc. Durante el período analizado se publicaron 1381 trabajos de ellos el 78.2 por ciento son de investigación y el 20.7 por ciento son revisiones, predominan los trabajos de Toxicología experimental (40.3 por ciento), Toxicología clínica (16:3 por ciento), Métodos analíticos 13 por ciento) estando las demás secciones mucho más pobremente representadas. El 52.3 por ciento o de los trabajos publicados proceden de departamentos universitarios, predominan los trabajos firmados por cuatro o más autores (63.9 por ciento), siendo la relación autor trabajo 3.81 ñ 0.11. (AU)

Medical devices; clinical chemistry and clinical toxicology devices; classification of the breath nitric oxide test system. Final rule.

The Food and Drug Administration (FDA) is classifying the breath nitric oxide test system into class II (special controls). The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (the SMDA), and the Food and Drug Administration Modernization Act of 1997 (FDAMA). The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document that will serve as the special control for the device.

From clinical to human toxicology: linking animal research and risk assessment in man.

Since the 1960s, clinical toxicologists have primarily focused on acute poisonings. This proved very successful as the prognosis markedly improved with the use of resuscitation methods, evidence-based management and new antidotes. This latter area was the first major instance linking animal research and clinical toxicology, as illustrated with N-acetyl-cysteine or specific antibodies. Simultaneously the evolution of poison centers was a critical turning point as '2nd generation' centers are increasingly involved in risk assessment and toxicovigilance. Human toxicology is a broader area in that it is also involved in the toxicity evaluation of xenobiotics with the resulting need to link animal research and risk assessment to match the results of preclinical studies with clinical observations. However, this is not an easy task as experimental and clinical toxicologists seldom share ideas and expertise. Immunotoxicology is an example of this situation. Most of the available data on immunosuppression was obtained in animals and not in man, whereas allergic reactions have been extensively investigated in man, but overlooked in animals until recently. One of the major challenges facing toxicology is to bridge the gap between animal research and risk assessment in man. Human toxicology is expected to play a role in taking up this challenge.

Case studies in the use of toxicological measures in epidemiological studies.

One of the major limitations in environmental epidemiological studies investigating associations between chemical exposures and the risk of disease is the use of crude exposure metrics. This increases the risk of exposure misclassification, reducing the chance of finding a real association, where one exists. In environmental epidemiological studies, surrogate exposure measures, such as time living in a contaminated area, do not adequately reflect the true nature and/or degree of real exposure to the chemical substance(s) of interest. Also, as they are not quantitative measures of absorbed dose, the data provided by such measures cannot give numerical measures of a dose response relationship, limiting their use in quantitative risk assessment. In epidemiological studies, biological measures of exposure should be used, if available, as they are close to the target organ dose and provide greater precision in risk estimates and dose response relationships. Examples are the measurement of speciated arsenic in the urine of subjects when investigating health effects from arsenic exposure, and the use of breast milk lipid concentration to measure body burden when conducting epidemiological studies of health effects from persistent lipophilic compounds, such as the endocrine disruptors. This paper discusses the main uses of such exposure measures, using several case studies, their limitations and some challenges in the future for toxicologists to develop more suitable measures for epidemiologists to use in population studies.

La enseñanza de la toxicología en las ciencias biosanitarias del siglo XXI / The role of toxicology in health sciences in the XXI century

La Toxicología, en la actualidad, está alcanzando una gran trascendencia social debido al gran número de sustancias químicas comercializadas y su posible impacto sobre la salud pública y ambiental, lo cual ha conducido al desarrollo de estrategias de evaluación de riesgos con fines normativos (Toxicología reguladora). Por otro lado, está dirigiendo también su atención hacia los efectos crónicos por exposición a bajas concentraciones de sustancias químicas, donde la evaluación de riesgos tóxicos cobra especial relevancia en términos de monitorización biológica y epidemiología molecular (Toxicología preventiva). En tercer lugar, la Toxicología se ha beneficiado en gran medida de los avances en Biología molecular y celular, lo que le ha permitido profundizar más en los mecanismos de acción tóxica y relacionarse estrechamente con la patogenia de enfermedades tumorales y neurodegenerativas (Toxicología mecanicista). Bajo estas premisas, y desde una perspectiva personal, realizo una reflexión sobre la orientación futura de la enseñanza de la Toxicología en ciencias biosanitarias y en base a qué planteamientos. Especial interés se presta a la enseñanza de pregrado en Medicina, Farmacia y Ciencia y tecnología de los alimentos, discutiendo tanto la orientación de sus contenidos teóricos como la introducción de tecnología bioinformática en la enseñanza práctica. Finalmente, se abordará la perspectiva futura de la formación de expertos en Toxicología, fundamentalmente a través de la enseñanza de tercer ciclo y bajo un contexto de armonización de la carrera a nivel europeo (AU)