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.

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.

"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.

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.

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.

Toxicological profiles: draft for public comment: public comment periodo ends: february 23, 2003

Os perfis toxicológicos ATSDR sucintamente caracterizar a toxicológicos e adversos efeitos de informação sobre saúde para a Descrito substância perigosa nelas. Cada peer-reviewed identificador de perfil e uma revisão da literatura-chave que descrevem propriedades de uma substância perigosa toxicológicos. Literatura pertinente outros também é apresentado, mas é menos Descrito em detalhes do que os estudos fundamentais. O perfil não se destina a ser um documento exaustivo, no entanto, as fontes mais abrangente de informação especializados são referenciados. (AU)

Toxico on: toxicologia Online

Traz a ToxicOn primeira base de dados em toxicologia de urgência em formato eletrônico e em língua portuguesa disponível para profissionais e instituições da área de saúdo do país. E conta com informação atualizada sobre os mais diversos agentes tóxicos, tais como, medicamentos, pesticidas (agrícolas e domésticos), produtos químicos e industriais, raticidas, metais, drogas de abuso, domissanitários, plantas tóxicas e animais peçonhentos, entre outros. (AU)

ATSDR ToxiProfiles 2002

Trabalha com "Perfis toxicológicos" para substâncias perigosas encontradas em Lista de Prioridades Nacionais (NPL). Essas substâncias perigosas são classificados com base na freqüência de ocorrência em locais NPL, toxicidade e potencial de exposição humana.Os Perfis toxicológicos são desenvolvidos em duas etapas: Projetos: Os perfis toxicológicos são primeiramente produzidos como rascunhos; e Finais: Após o período de comentários de 90 dias, considera ATSDR incorporando todos os comentários para documentos

Avaliação das consequências da 'Lei dos Agrotóxicos' nas intoxicações e nas classificações toxicológica e de potencial de periculosidade ambiental no período de 1990 a 2000 / Evaluation of the "Pesticide Law" consequences on intoxications and on toxicological and environmental potential hazard classifications from 1990 to 2000

Objetivo: A Lei 7802/89 (Lei dos Agrotóxicos) foi considerada importante avanço para enfrentar problemas ambientais e de saúde provocados por agrotóxicos. Este estudo buscou avaliar o impacto da Lei e respectiva regulamentação na classificação toxicológica, na classificação de potencial de periculosidade ambiental dos agrotóxicos e nas intoxicações registradas. Métodos: Analisou-se a correlação entre vendas de agrotóxicos e registros de intoxicações no Brasil, de 1985 a 1999, utilizando Coeficiente de Correlação Linear de Pearson e Análise de Regressão. Os testes Qui-Quadrado de Tendência em Dados Ordenáveis e Coeficiente de Kappa foram utilizados para comparar o conjunto de substâncias que estava registrado em 1990 com o que estava registrado em 2000, segundo a classificação de periculosidade da Organização Mundial da Saúde. Analisaram-se as culturas/produtos de destinação permitidas, a classificação toxicológica e a de periculosidade ambiental dos produtos registrados após a Lei. Resultados: A correlação entre vendas e intoxicações foi positiva (r=0,82 ; p<0,0001). Obteve-se equação intox = 0,00236 x vendas (US$ 1,000.00) que permite estimar intoxicações registradas segundo vendas de agrotóxicos (R2=0,95; F=253,48; p<0,0001). Não houve diferenças significativas na classificação toxicológica e ambiental dos conjuntos de substâncias registradas antes-depois da Lei. Os registros posteriores à Lei continuaram privilegiando culturas de maior expressão econômica e agrotóxicos derivados de substâncias registradas antes da Lei. Produtos mais tóxicos foram registrados para finalidade que contava com outros menos tóxicos. Conclusões: Após dez anos não se consolidaram avanços esperados com a Lei. Recomendou-se: aplicar legislação com maior eficácia, priorizar registros de menor impacto, restringir produtos de maior periculosidade

Objective. The 1989 Brazilian's pesticide legislation (Law n° 7802/89) was considered an important improvement to control environmental and health problems. This study aimed to evaluate the impact of the law and it's regulations to the toxicological and environmental classifications of pesticides by hazard and to the notified poisonings. Methods. Pearson Correlation and Regression Analysis were used to evaluate the correlation between pesticide sales and notified intoxications in Brazil, from 1985 to 1999. Kappa Coefficient and Ridit Analysis (Relative Identified Distribution Analysis) were used to compare the WHO (World Health Organization) classification of pesticides by hazard of the group of chemicals that was registered in 1990 and the group registered in 2000. The toxicological and environmental classifications and the allowed destinations of the pesticides that were registered after the law were also analyzed. Results. The correlation among sales of pesticides and poisonings was positive (r=0,82 ; p<0,0001). The equation obtained make possible to estimate poisonings notifications using values of pesticides sales (R =0,95; F=253,48; p<0,0001): intox = 0,00236 x sales (US$ 1,000.00) . No significant toxicological and environmental classifications differences were identified between the groups of pesticides that were registered in 1990 and 2000. The most economical expressive crops received the majority of the registers. More toxic pesticides were registered to destinations that had less toxic ones. Conclusions. After ten years of Law it was not possible to consolidate the expected improvements. Recommendations included: enforcement of the law, priority to less risky pesticides, restriction to more toxic ones

Deterioro fúngico de los alimentos e impactos económicos de las micotoxinas / Fungal biodeterioration of food and economic impact of mycotoxins

Las micotoxinas son metabólitos fúngicos que se encuentran en una variedad de sustratos incluyendo piensos y alimentos. Ellos causan problemas en la salud humana y animal especialmente, causan pérdidas económicas significativas. La toxicidad de las micotoxinas en los animales varía desde muerte aguda a enfermedades crónicas e interferencia con la eficiencia reproductiva. Las aflatoxinas causan daño del hígado, cáncer, disminución de la producción de leche, huevos e inmunosupresión. Las aflotoxinas son de gran importancia en las micotoxicosis en humanos ya que son potencialmente carcinogénicas. Los principales estudios epidemiológicos relacionados con las afloxinas han sido llevados a cabo en Asia y africa, y algunos han mostrado una asociación positiva entre niveles de aflatoxinas en los alimentos y presencia de enfermedades. Las pérdidas económicas debido a las micotoxinas y en especial a aflatoxinas son multifacéticas e involucra al cultivo directamente y animales domésticos. La incidencia de las micotoxinas varía entre sustratos, condiciones climáticas y regiones. Por estas razones, la importancia económica de las micotoxinas es difícil de cuantificar

Envenenamiento mortal causado por el aceite de epazote: chenopodium graveolens / Fatal poisoning caused by epazote oil: chenopodium graveolens

Se presenta el caso de una niña de 2 años y 9 meses de edad, a quien una curandera indica la administración de aceite de epazote (aceite de quenopodio) como vermífugo, en dos tomas de 20 ml cada una. Después de la segunda manifiesta coma profundo, convulciones, midriasis, apnea, acidosis metabólica, choque neurogénico y muerte. ElEEG mostró un trazo sugestivo de encefalopatía, la TAC con imagen de edema cerebral y colapso ventricular. El estudio postmortem ratificó el edema cerebral y microscópicamente evidenció necrosis neuronal difusa; otros hallazgos fueron neumonía, enteritis, peicolangitis, pancreatitis incipiente y necrosisi tubular, el análisis fitoquímico del aceite identificó ascaridol, principio activo de las quenopodáceas, en cantidad 39 mg/ml (1,560 mg en los 40 ml ingeridos) y a chenopodium graveolens como la planta de la que se obtuvo el aceite, conforme al método como históricamente se adminstraba el aceite, la paciente debió haber ingerido una dosis total de ascaridol de 60 mg, por lo que la cantidad administrada fue 26 veces superior, además que excedía 56 por ciento la dosis de 1,000 mg, informada como letal en humanos.