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1.
Aquat Toxicol ; 222: 105478, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32278258

RESUMO

This study was undertaken to systematically assess the utilities and performance of ontology-based semantic analysis in adverse outcome pathway (AOP) research. With an increasing number of AOPs developed by scientific domain experts to organize toxicity information and facilitate chemical risk assessment, there is a pressing need for objective approaches to evaluate the biological coherence and quality of these AOPs. Powered by ontologies covering a wide range of biological domains, abundant phenotypic data annotated ontologically, and some sophisticated knowledge computing tools, semantic analysis has great potential in this area of application. With the events in the AOP-Wiki first annotated into logical definitions and then grouped into phenotypic profiles by individual AOPs, the coherence and quality of AOPs were assessed at several levels: paired key event relationships (KER), all possible event pair combinations within AOPs, and the phenotypic profiles of AOPs, genes, biological pathways, human diseases, and selected chemicals. The semantic similarities were assessed at all these levels based on a unified cross-species vertebrate phenotype ontology encompassing the logical definitions of AOP events as well as many other domain ontologies. A substantial number of KERs and AOPs in the AOP-Wiki were found to be semantically coherent. These same coherent AOPs also mapped to many more genes, pathways, and diseases biologically aligned with the intended chain of events therein leading to their respective adverse outcomes. Significantly, these findings imply that semantic analysis should also have utilities in developing future AOPs by selecting candidate events from either the existing AOP-Wiki events or a broader collection of ontology terms semantically similar to the molecular initiating events or adverse outcomes of interest. In addition, semantic analysis enabled AOP networks to be constructed at the level of phenotypic profiles based on similarities, complementing those based on event sharing by bringing genes, pathways, diseases, and chemicals into the networks too-thus greatly expanding the biological scope and our understanding of AOPs.


Assuntos
Rotas de Resultados Adversos , Pesquisa Biomédica/métodos , Semântica , Toxicologia/métodos , Animais , Ontologias Biológicas , Humanos , Fenótipo , Medição de Risco
2.
Toxicol Lett ; 325: 62-66, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109533

RESUMO

Risk assessment for mixtures of chemicals requires to investigate the magnitude of their potential adverse effects on living organisms. This is usually done by assessing how experimental toxicological mixture data depart from the model of Loewe additivity. Several recent scientific studies propose to perform this task using an ad hoc method known as model deviation ratio (MDR) method. Moreover, the first official European regulatory document for the study of combined exposures explicitly recommends the use of the MDR method (EFSA Scientific Committee et al. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. EFSA Journal, 2019). We show here that the MDR method is not rooted in statistical principles and can lead to erroneous claims. We show however that the distribution of the MDR can be evaluated by simulations and show how this allows us to devise and carry out a bona fide statistical test. The proposed method accounts for uncertainty in the estimation of ED/EC50 and does not require a minimum sample size. The computer code developped in this study is made available as an R package called MDR.


Assuntos
Misturas Complexas/toxicidade , Relação Dose-Resposta a Droga , Modelos Estatísticos , Toxicologia/métodos , Animais , Humanos , Medição de Risco , Toxicologia/estatística & dados numéricos
4.
Environ Sci Pollut Res Int ; 27(2): 1267-1275, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745782

RESUMO

There have been numerous environmental geochemistry studies using chemical, geological, ecological, and toxicological methods but each of these fields requires more subject specialist rigour than has generally been applied so far. Field-specific terminology has been misused and the resulting interpretations rendered inaccurate. In this paper, we propose a series of suggestions, based on our experience as teachers, researchers, reviewers, and editorial board members, to help authors to avoid pitfalls. Many scientific inaccuracies continue to be unchecked and are repeatedly republished by the scientific community. These recommendations should help our colleagues and editorial board members, as well as reviewers, to avoid the numerous inaccuracies and misconceptions currently in circulation and establish a trend towards greater rigour in scientific writing.


Assuntos
Ecologia , Monitoramento Ambiental/métodos , Compostos Orgânicos , Toxicologia/métodos
5.
Environ Health Perspect ; 127(12): 125002, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834829

RESUMO

BACKGROUND: Numerous types of rapid toxicity or exposure assays and platforms are providing information relevant to human hazard and exposure identification. They offer the promise of aiding decision-making in a variety of contexts including the regulatory management of chemicals, evaluation of products and environmental media, and emergency response. There is a need to consider both the scientific validity of the new methods and the values applied to a given decision using this new information to ensure that the new methods are employed in ways that enhance public health and environmental protection. In 2018, a National Academies of Sciences, Engineering, and Medicine (NASEM) workshop examined both the toxicological and societal aspects of this challenge. OBJECTIVES: Our objectives were to explore the challenges of adopting new data streams into regulatory decision-making and highlight the need to align new methods with the information and confidence needs of the decision contexts in which the data may be applied. METHODS: We go beyond the NASEM workshop to further explore the requirements of different decision contexts. We also call for the new methods to be applied in a manner consistent with the core values of public health and environmental protection. We use the case examples presented in the NASEM workshop to illustrate a range of decision contexts that have applied or could benefit from these new data streams. Organizers of the NASEM workshop came together to further evaluate the main themes from the workshop and develop a joint assessment of the critical needs for improved use of emerging toxicology tools in decision-making. We have drawn from our own experience and individual decision or research contexts as well as from the case studies and panel discussions from the workshop to inform our assessment. DISCUSSION: Many of the statutes that regulate chemicals in the environment place a high priority on the protection of public health and the environment. Moving away from the sole reliance on traditional approaches and information sources used in hazard, exposure, and risk assessment, toward the more expansive use of rapidly acquired chemical information via in vitro, in silico, and targeted testing strategies will require careful consideration of the information needed and values considerations associated with a particular decision. In this commentary, we explore the ability and feasibility of using emerging data streams, particularly those that allow for the rapid testing of a large number of chemicals across numerous biological targets, to shift the chemical testing paradigm to one in which potentially harmful chemicals are more rapidly identified, prioritized, and addressed. Such a paradigm shift could ultimately save financial and natural resources while ensuring and preserving the protection of public health. https://doi.org/10.1289/EHP4745.


Assuntos
Saúde Ambiental , Toxicologia/métodos , Simulação por Computador , Tomada de Decisões , Exposição Ambiental , Humanos , Saúde Pública , Medição de Risco
6.
Mutat Res ; 847: 403022, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699343

RESUMO

We live in an era of 'big data', where the volume, velocity, and variety of the data being generated is increasingly influencing the way toxicological sciences are practiced. With this in mind, a workgroup was formed for the 2017 International Workshops on Genotoxicity Testing (IWGT) to consider the use of high information content data in genetic toxicology assessments. Presentations were given on adductomics, global transcriptional profiling, error-reduced single-molecule sequencing, and cellular phenotype-based assays, which were identified as methodologies that are relevant to present-day genetic toxicology assessments. Presenters and workgroup members discussed the state of the science for these methodologies, their potential use in genetic toxicology, current limitations, and the future work necessary to advance their utility and application. The session culminated with audience-assisted SWOT (strength, weakness, opportunities, and threats) analyses. The summary report described herein is structured similarly. A major conclusion of the workgroup is that while conventional regulatory genetic toxicology testing has served the public well over the last several decades, it does not provide the throughput that has become necessary in modern times, and it does not generate the mechanistic information that risk assessments ideally take into consideration. The high information content assay platforms that were discussed in this session, as well as others under development, have the potential to address aspect(s) of these issues and to meet new expectations in the field of genetic toxicology.


Assuntos
Testes de Mutagenicidade/métodos , Animais , Big Data , Linhagem Celular , Adutos de DNA/análise , Código de Barras de DNA Taxonômico/métodos , Dano ao DNA , Mineração de Dados , Avaliação Pré-Clínica de Medicamentos , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Processamento de Imagem Assistida por Computador , Espectrometria de Massas/métodos , Metanálise como Assunto , Camundongos , Testes de Mutagenicidade/normas , Fenótipo , Imagem Individual de Molécula , Toxicologia/métodos , Transcriptoma
7.
Ann Epidemiol ; 38: 65-69, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564485

RESUMO

PURPOSE: Classification of overdose deaths is often geographically and demographically inconsistent. Incomplete surveillance records may distort estimates of drug overdose rates across time and place. We examined incomplete toxicology reporting among drug overdose decedents by demographic and geographic characteristics, measuring changes in missingness rates and their associations with decedent characteristics over time. METHODS: We estimated the percentage of overdose deaths reported in the National Vital Statistics System with missing toxicology results from 2010 to 2016, overall and by decedents' demographic and geographic characteristics. Multilevel logistic regression models evaluated prevalence of missingness by decedent characteristics, accounting for geographic clustering. RESULTS: Overall, 20.3% of death certificates did not indicate a specific drug, declining from 24.4% in 2010 to 14.6% in 2016. Deaths were less likely to have missing information if they occurred in counties with medical examiners versus coroners. Female decedents were more likely to have missing information than males, as were non-Hispanic whites compared with Hispanics and non-Hispanic blacks. CONCLUSIONS: The percentage of deaths with missing toxicology information declined over time, but demographic and geographic differences in missingness persist. This yields detection biases that skew temporal trends and understanding of groups impacted by the opioid epidemic.


Assuntos
Analgésicos Opioides/envenenamento , Analgésicos Opioides/toxicidade , Médicos Legistas , Coleta de Dados/métodos , Atestado de Óbito , Overdose de Drogas/mortalidade , Transtornos Relacionados ao Uso de Opioides/mortalidade , Medicamentos sob Prescrição/envenenamento , Toxicologia/estatística & dados numéricos , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Médicos Legistas/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Toxicologia/métodos , Toxicologia/normas , Estados Unidos , Adulto Jovem
8.
Toxicol Lett ; 317: 68-81, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580885

RESUMO

Skin sensitization, frequently leading to allergic contact dermatitis (ACD), is authenticated to be a significant endpoint in the field of drug discovery and cosmetics. The initiation of ACD, also known as the skin sensitization mechanism, has been documented as an adverse outcome pathway (AOP), which can be studied experimentally and computationally. In this study, we collected 154 haptens and applied systems toxicology methods to develop a reaction-substructure-compound- target-pathway network system. For the collected haptens, their key substructures were identified and associated with their protein binding reactions. The targets of haptens, including the known targets collected from four databases and the potential targets predicted via our balanced substructure-drug-target network-based inference (bSDTNBI) method, were matched to skin proteins to obtain skin targets. The dermatitis-related pathways were enriched and were subject to literature verification. The network system we developed can be applied to predict the reactions, targets and pathways of new haptens, which contributed to evaluating chemical safety and optimizing chemical structures. The study of skin sensitization mechanism is helpful for understanding the skin immunity and resisting ACD.


Assuntos
Dermatite Alérgica de Contato/etiologia , Haptenos/toxicidade , Pele/efeitos dos fármacos , Biologia de Sistemas , Toxicologia/métodos , Animais , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/metabolismo , Haptenos/química , Humanos , Estrutura Molecular , Ligação Proteica , Mapas de Interação de Proteínas , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Relação Estrutura-Atividade
9.
Mutat Res ; 846: 503094, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585631

RESUMO

In contributing to this Special Issue of Mutation Research dedicated to Professor Bruce N. Ames in recognition of his 90th birthday in December 2018, we intend to portray the importance not only of the Ames Salmonella/mammalian-microsome mutagenicity assay in some of our studies over the years, but also the importance of the insight that Bruce Ames brought to the field of genetic toxicology.


Assuntos
Testes de Mutagenicidade , Salmonella/efeitos dos fármacos , Ativação Metabólica , Poluentes Ocupacionais do Ar/toxicidade , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Flavonoides/química , Flavonoides/toxicidade , Engenharia Genética , Humanos , Microssomos Hepáticos/enzimologia , Estrutura Molecular , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Nevirapina/química , Nevirapina/toxicidade , Exposição Ocupacional , Quercetina/toxicidade , Ratos , Salmonella/genética , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Especificidade da Espécie , Toxicologia/métodos , Urina/química
11.
Environ Int ; 131: 105060, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31377600

RESUMO

In silico methods and models are increasingly used for predicting properties of chemicals for hazard identification and hazard characterisation in the absence of experimental toxicity data. Many in silico models are available and can be used individually or in an integrated fashion. Whilst such models offer major benefits to toxicologists, risk assessors and the global scientific community, the lack of a consistent framework for the integration of in silico results can lead to uncertainty and even contradictions across models and users, even for the same chemicals. In this context, a range of methods for integrating in silico results have been proposed on a statistical or case-specific basis. Read-across constitutes another strategy for deriving reference points or points of departure for hazard characterisation of untested chemicals, from the available experimental data for structurally-similar compounds, mostly using expert judgment. Recently a number of software systems have been developed to support experts in this task providing a formalised and structured procedure. Such a procedure could also facilitate further integration of the results generated from in silico models and read-across. This article discusses a framework on weight of evidence published by EFSA to identify the stepwise approach for systematic integration of results or values obtained from these "non-testing methods". Key criteria and best practices for selecting and evaluating individual in silico models are also described, together with the means to combining the results, taking into account any limitations, and identifying strategies that are likely to provide consistent results.


Assuntos
Simulação por Computador , Modelos Químicos , Medição de Risco/métodos , Toxicologia/métodos , Testes de Toxicidade
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(8): 843-850, 2019 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-31378047

RESUMO

The number of new chemicals increases tremendously annually, while traditional time-and cost-consuming toxicity tests based on animals with the uncertainty of extrapolation could not meet the demand of hazard identification and risk assessment. Thus,the evolution of methodology for toxicity tests is desired to fill up the huge data gap. With the rapid development of life science and technology,the insights into the nature of life and pathology of diseases have changed and systematic toxicology has emerged. Equipping with the advantages of multi-disciplinary study,systematic toxicology expands the research fields of toxicology and accelerates the speed of illustrating molecular mechanism of environmental xenobiotics, biomarkers screening and validation, and the development of new methods for risk assessment. Toxicogenomics and computational toxicology analysis are the major technology of systematic toxicology. Computational toxicology integrates data from toxicogenomics to construct multi-levels and multi-dimensional models for quantitative exposure risk assessment. This research summarized the research progress of computational toxicology from the aspects of research strategies, common databases, analytical tools, research methods and application, so as to provide references for the risk assessment of chemical substances.


Assuntos
Medição de Risco/métodos , Testes de Toxicidade/métodos , Toxicologia/métodos , Animais , Biomarcadores , Projetos de Pesquisa , Toxicogenética
13.
Toxicol Pathol ; 47(5): 574-576, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31303126

RESUMO

In the article "Opinion on Designation of Adverse and Nonadverse Histopathological Findings in Toxicity Studies: The Pathologist's Dilemma," the authors Gopinath and Mowat provide a framework for designation of adversity supplemented with photomicrographic examples. Given that adversity designation can significantly impact the no observed adverse effect level and clinical trial design, it is important to carefully consider all of the criteria by which such assignments are made. We highlight some of the specific assertions within the article that could benefit from a more detailed discussion. Our primary criticism surrounds the authors' primary reliance on histopathology in isolation for adversity designation, which in our opinion provides an overly simplified depiction of the process. We provide additional perspective on how context beyond histopathology often plays a critical role in adversity designation and highlight areas where inclusion of some of these scenarios would have provided the reader a more realistic view of the complex process of assigning adversity. * This is an opinion article submitted to the Toxicologic Pathology Forum. It represents the views of the authors. It does not constitute an official position of the Society of Toxicologic Pathology, British Society of Toxicological Pathology, or European Society of Toxicologic Pathology, and the views expressed might not reflect the best practices recommended by these Societies. This article should not be construed to represent the policies, positions, or opinions of their respective organizations, employers, or regulatory agencies.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Patologia/métodos , Toxicologia/métodos , Animais , Humanos , Nível de Efeito Adverso não Observado , Patologia/normas , Toxicologia/normas
14.
Toxicol Lett ; 314: 164-171, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31330168

RESUMO

In routine regulatory toxicology studies, the anatomic pathology endpoints are frequently the most significant element of the study data. They may profoundly influence subsequent clinical development and use of a test article, with implications for both human safety and for the fate of key commercial assets. Unfortunately (in common with other perceptual medical specialties), anatomic pathology data are also among the most subjective endpoints in regulatory toxicology studies - a challenge magnified by the fact that not only the diagnostic data but the anatomic pathologist's interpretation of it in their narrative report represent raw data within a regulated study (United States Federal Register, 1987). A strategy for minimizing and managing the risk of misdiagnosis/misinterpretation of pathology data is critical for any preclinical toxicology development program and is a collaborative approach between study directors, study monitors and toxicologists and toxicologic pathologists. The article provides a basic understanding of the sources of error and limitations of anatomic pathology evaluation, a starting point for troubleshooting and a basis for a sound management strategy. It describes common reasons for unexpected or inconsistent pathology findings and sets out to provide a framework for toxicologists to approach commissioning and critically evaluating their pathology data, and for identifying situations where additional third-party advice and review may be justified.


Assuntos
Confiabilidade dos Dados , Avaliação Pré-Clínica de Medicamentos/métodos , Microscopia , Patologia/métodos , Toxicologia/métodos , Animais , Comportamento Cooperativo , Humanos , Comunicação Interdisciplinar , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fluxo de Trabalho
15.
Med Sci (Paris) ; 35(6-7): 544-548, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31274084

RESUMO

Since a few decades, a new invertebrate animal model has emerged in toxicology studies: the planarian. This non-parasitic flatworm, from phylum Platyhelminthes, has an amazing regenerative capacity and has been described as "immortal under the edge of the knife" in 1814 by Dalyell. This formidable capacity is due to the abundance of stem cells called neoblasts, allowing for a tiny fragment equivalent to 1/279th of the size of the planarian to generate a whole animal. The planarian has also a human-like nervous system with several neurotransmitters and has been used to evaluate developmental perturbations and neurotoxicity. This review summarizes the main planarian toxicology studies and highlights the potential of this original animal model for research.


Assuntos
Modelos Animais , Planárias , Testes de Toxicidade/tendências , Toxicologia/métodos , Animais , Modelos Animais de Doenças , Inseticidas/toxicidade , Metais/toxicidade , Síndromes Neurotóxicas/patologia , Compostos Organometálicos/toxicidade , Planárias/fisiologia , Testes de Toxicidade/métodos , Toxicologia/tendências
16.
Reprod Toxicol ; 88: 56-66, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31348994

RESUMO

Recently several OECD test guidelines were updated to include thyroid hormone measurements for assessing endocrine disruptor potency, which led to an imperative need to align interpretation of these results by the different stakeholders. We therefore evaluated 124 repro screening studies, which showed in 38% of the studies a statistical significant finding for T4 in at least one treatment group, probably due to disturbances of normal homeostasis causing high variation. Consequently, for a thorough evaluation it is extremely important to take the historical control range into account. In conclusion, the current testing approach is not providing specific information needed to assess endocrine disruption, as too often a statistical significant finding is noted and as down-stream adverse effects are not evaluated. Therefore, major modifications are urgently needed. Instead of extending the in vivo experiments, it should be investigated if in vitro assessments will provide more relevant information on human endocrine disruptor potential.


Assuntos
Guias como Assunto/normas , Organização para a Cooperação e Desenvolvimento Econômico/normas , Hormônios Tireóideos/sangue , Animais , Disruptores Endócrinos/toxicidade , União Europeia , Feminino , Humanos , Masculino , Ratos , Glândula Tireoide/efeitos dos fármacos , Tireotropina/sangue , Tiroxina/sangue , Toxicologia/métodos , Toxicologia/normas , Tri-Iodotironina/sangue , Estados Unidos
17.
Reprod Toxicol ; 89: 124-129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288076

RESUMO

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.


Assuntos
Alternativas ao Uso de Animais/métodos , Bases de Dados Factuais/tendências , Reprodução/efeitos dos fármacos , Toxicologia/métodos , Alternativas ao Uso de Animais/tendências , Animais , Berlim , Medição de Risco , Especificidade da Espécie , Terminologia como Assunto , Toxicologia/tendências
18.
Toxicol Pathol ; 47(5): 564-573, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291835

RESUMO

In this opinion piece, we discuss some proposed principles for designating adversity and nonadversity of histopathological changes. The suggested approach categorizes the classes of findings noted in toxicity studies with illustrations and examples and suggests adversity or nonadversity for each class, in the authors' opinions, with rationales. Although the suggestions and examples offered in this opinion piece are generally in agreement with Society of Toxicologic Pathology best practices guideline on adversity, the authors suggest and highlight occasional divergences and differences of opinion. This is because making an adversity call is a complex and challenging topic that is difficult to simplify. Some of the challenges in deciding on adversity are discussed, especially those related to making an adversity call on a histopathological finding in isolation, based on the nature and extent of severity. The authors demonstrate some of these situations with examples. Finally, the authors suggest, in contrast to the guidelines, occasional use of a separate category for findings that are less easily classified. *This is an opinion article submitted to the Toxicologic Pathology Forum. It represents the views of the author(s). It does not constitute an official position of the Society of Toxicologic Pathology, British Society of Toxicological Pathology, or European Society of Toxicologic Pathology, and the views expressed might not reflect the best practices recommended by these Societies. This article should not be construed to represent the policies, positions, or opinions of their respective organizations, employers, or regulatory agencies.


Assuntos
Patologia/normas , Toxicologia/normas , Congressos como Assunto , Patologia/métodos , Guias de Prática Clínica como Assunto , Toxicologia/métodos
19.
Reprod Toxicol ; 89: 145-158, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31340180

RESUMO

The Toxicity Reference Database (ToxRefDB) structures information from over 5000 in vivo toxicity studies, conducted largely to guidelines or specifications from the US Environmental Protection Agency and the National Toxicology Program, into a public resource for training and validation of predictive models. Herein, ToxRefDB version 2.0 (ToxRefDBv2) development is described. Endpoints were annotated (e.g. required, not required) according to guidelines for subacute, subchronic, chronic, developmental, and multigenerational reproductive designs, distinguishing negative responses from untested. Quantitative data were extracted, and dose-response modeling for nearly 28,000 datasets from nearly 400 endpoints using Benchmark Dose (BMD) Modeling Software were generated and stored. Implementation of controlled vocabulary improved data quality; standardization to guideline requirements and cross-referencing with United Medical Language System (UMLS) connects ToxRefDBv2 observations to vocabularies linked to UMLS, including PubMed medical subject headings. ToxRefDBv2 allows for increased connections to other resources and has greatly enhanced quantitative and qualitative utility for predictive toxicology.


Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais/tendências , Substâncias Perigosas/toxicidade , Toxicologia/métodos , Animais , Biologia Computacional/tendências , Relação Dose-Resposta a Droga , Substâncias Perigosas/química , Substâncias Perigosas/classificação , Modelos Biológicos , Software , Toxicologia/tendências , Estados Unidos , United States Environmental Protection Agency
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