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1.
Arch Toxicol ; 96(3): 711-741, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35103818

RESUMO

Organ-on-chip (OoC) technology is full of engineering and biological challenges, but it has the potential to revolutionize the Next-Generation Risk Assessment of novel ingredients for consumer products and chemicals. A successful incorporation of OoC technology into the Next-Generation Risk Assessment toolbox depends on the robustness of the microfluidic devices and the organ tissue models used. Recent advances in standardized device manufacturing, organ tissue cultivation and growth protocols offer the ability to bridge the gaps towards the implementation of organ-on-chip technology. Next-Generation Risk Assessment is an exposure-led and hypothesis-driven tiered approach to risk assessment using detailed human exposure information and the application of appropriate new (non-animal) toxicological testing approaches. Organ-on-chip presents a promising in vitro approach by combining human cell culturing with dynamic microfluidics to improve physiological emulation. Here, we critically review commercial organ-on-chip devices, as well as recent tissue culture model studies of the skin, intestinal barrier and liver as the main metabolic organ to be used on-chip for Next-Generation Risk Assessment. Finally, microfluidically linked tissue combinations such as skin-liver and intestine-liver in organ-on-chip devices are reviewed as they form a relevant aspect for advancing toxicokinetic and toxicodynamic studies. We point to recent achievements and challenges to overcome, to advance non-animal, human-relevant safety studies.


Assuntos
Dispositivos Lab-On-A-Chip , Medição de Risco/métodos , Toxicologia/métodos , Alternativas aos Testes com Animais/métodos , Alternativas aos Testes com Animais/tendências , Humanos , Intestinos/metabolismo , Fígado/metabolismo , Medição de Risco/tendências , Pele/metabolismo , Técnicas de Cultura de Tecidos , Toxicologia/tendências
2.
Regul Toxicol Pharmacol ; 117: 104786, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32976858

RESUMO

The 90-day toxicity study is one of the studies used in the safety assessment of food ingredients, medicines or other chemical substances. This paper reviews the current role of the 90-day oral toxicity study in European regulatory dossiers of chemicals by reviewing EU legislation and EU and OECD guidance documents. Regulatory provisions with regard to necessity, objectives and design of such 90-day toxicity studies vary between the different sectors addressed in this review. Most often the 90-day study is expected to be part of the standard test battery used for chemical risk assessment, without necessarily being a legal requirement and its objectives may vary between regulatory domains. Exceptions, when a 90-day study is not required are spelled out in the chemicals legislation and for food contact materials. The sectorial study design requirements of the 90-day toxicity study are very often embedded in the OECD TG 408 protocol. Differences in study objectives are not necessarily reflected in specific study designs. Considering the call for the reduction of using experimental animals for scientific purposes and the fact that a 90-day study may serve different purposes, consistency between the necessity to conduct such a study, its objectives and the study design to achieve these objectives may improve judicious use of laboratory animals. Thus there may be an opportunity to reflect and further optimise the design of in vivo toxicology studies, such as the 90-day study. This should be based on a systematic analysis of past studies and risk assessments.


Assuntos
Alternativas aos Testes com Animais/legislação & jurisprudência , Alternativas aos Testes com Animais/normas , União Europeia , Organização para a Cooperação e Desenvolvimento Econômico/legislação & jurisprudência , Organização para a Cooperação e Desenvolvimento Econômico/normas , Testes de Toxicidade/normas , Administração Oral , Alternativas aos Testes com Animais/tendências , Animais , Humanos , Organização para a Cooperação e Desenvolvimento Econômico/tendências , Medição de Risco , Roedores , Fatores de Tempo , Testes de Toxicidade/tendências
4.
Altern Lab Anim ; 48(1): 40-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32316753

RESUMO

In the 60 years since the publication of The Principles of Humane Experimental Technique, the Three Rs (Reduction, Refinement, Replacement) proposed by William Russell and Rex Burch have gradually been accepted throughout the world as ways of facing up to the ethical and scientific dilemmas involved in animal experimentation. However, the scale of animal use and the use of animals as models of humans has continued, seemingly almost unchallenged in much of the scientific community, despite the warnings about models, species differences and human variation spelled out in the The Principles. In this Comment, it is proposed that it is time to move away from the animal welfare focus of the Three Rs, in favour of a wider concept of humanity, which also embraces human welfare. In addition, since less than 10% of new drugs successfully pass from preclinical testing, which is highly reliant on animal procedures, to acceptance for clinical use, it is argued that the aim should not be to directly replace animal testing with non-animal methods with similar aims and which produce similar results, but to take advantage of developments in cell and molecular biology and in computer science, to devise new, different, appropriate, specific and intelligent stand-alone preclinical testing strategies that are applicable to particular human situations.


Assuntos
Experimentação Animal , Alternativas aos Testes com Animais , Bem-Estar do Animal , Projetos de Pesquisa , Experimentação Animal/normas , Alternativas aos Testes com Animais/tendências , Bem-Estar do Animal/normas , Bem-Estar do Animal/tendências , Animais , Humanos , Editoração , Projetos de Pesquisa/tendências
5.
Toxicology ; 436: 152421, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32119890

RESUMO

Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetics Regulation. This means that for the safety assessment of cosmetics, the necessary safety data for both the ingredients and the finished product can be drawn from validated (or scientifically-valid), so-called "Replacement methods". In view of the challenges for safety assessment without recourse to animal test data, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a workshop in February 2019 to discuss the key issues in regard to the use of animal-free alternative methods for the safety evaluation of cosmetic ingredients. This perspective article summarises the outcomes of this workshop and reflects on the state-of-the-art and possible way forward for the safety assessment of cosmetic ingredients for which no experimental animal data exist. The use and optimisation of "New Approach Methodology" that could be useful tools in the context of the "Next Generation Risk Assessment" and the strategic framework for safety assessment of cosmetics were discussed in depth.


Assuntos
Alternativas aos Testes com Animais/tendências , Cosméticos/efeitos adversos , Testes de Toxicidade/tendências , Animais , Simulação por Computador , Qualidade de Produtos para o Consumidor , Cosméticos/classificação , Cosméticos/farmacocinética , Difusão de Inovações , União Europeia , Previsões , Humanos , Modelos Biológicos , Medição de Risco , Relação Estrutura-Atividade
6.
Toxicol In Vitro ; 62: 104684, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31618670

RESUMO

The evaluation of tobacco products is complex due to a multitude of factors including product diversity, limited testing standards, and variability in user behavior. Alternative approaches in current testing paradigms have limitations that generally truncate their applicability beyond screening for hazard identification; this is also true for toxicological evaluations of tobacco products. In a regulatory context, results from tobacco product toxicity assessments are extrapolated to the in vivo condition to assess human health relevance at the individual and population level. A key limitation of alternative approaches is the difficulty and uncertainty in extrapolating results to adverse outcomes relevant to chronic tobacco exposures in humans. This difficulty and uncertainty are increased when comparing toxicological outcomes between tobacco products. Given that the interpretation and quantification of differences in assay results (e.g., mutagenicity) for tobacco product comparison may be inconclusive, the predictive value of these approaches for human risk of relevant downstream pathologies (e.g., carcinogenesis) can be limited. Development and validation of fit-for-purpose alternative approaches that are predictive of human toxicity and dose response assays with adequate sensitivity and specificity for product comparisons would help advance the field of predictive toxicology.


Assuntos
Alternativas aos Testes com Animais/legislação & jurisprudência , Alternativas aos Testes com Animais/tendências , Produtos do Tabaco/toxicidade , Animais , Sistemas Eletrônicos de Liberação de Nicotina , Humanos
8.
ALTEX ; 36(4): 523-534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664457

RESUMO

In the past 10 years, the public, private, and non-profit sectors have found agreement that hazard identification and risk assessment should capitalize on the explosion of knowledge in the biological sciences, moving away from in life animal testing toward more human-relevant in vitro and in silico methods, collectively referred to as new approach methodologies (NAMs). The goals for implementation of NAMs are to efficiently identify possible chemical hazards and to gather dose-response data to inform more human-relevant safety assessment. While work proceeds to develop NAMs, there has been less emphasis on creating decision criteria or showing how risk context should guide selection and use of NAMs. Here, we outline application scenarios for NAMs in different risk contexts and place different NAMs and conventional testing approaches into four broad levels. Level 1 relies solely on computational screening; Level 2 consists of high throughput in vitro screening with human cells intended to provide broad coverage of possible responses; Level 3 focuses on fit-for-purpose assays selected based on presumptive modes of action (MOA) and designed to provide more quantitative estimates of relevant dose responses; Level 4 has a variety of more complex multi-dimensional or multi-cellular assays and might include targeted in vivo studies to further define MOA. Each level also includes decision-appropriate exposure assessment tools. Our aims here are to (1) foster discussion about context-dependent applications of NAMs in relation to risk assessment needs and (2) describe a functional roadmap to identify where NAMs are expected to be adequate for chemical safety decision-making.


Assuntos
Alternativas aos Testes com Animais/tendências , Testes de Toxicidade/tendências , Animais , Biologia Computacional/métodos , Química Computacional/métodos , Ensaios de Triagem em Larga Escala , Humanos , Técnicas In Vitro , Mamíferos
10.
Altern Lab Anim ; 47(2): 71-81, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31319697

RESUMO

In Brazil, efforts towards the regulatory acceptance and implementation of innovative methods to replace experimental animal use in various fields began to gather force in 2008, with the approval of Law No. 11,794/2008 (the Arouca Law). This law represented a milestone, as it created the National Council for the Control of Animal Experimentation (CONCEA) to deal with the ethical and legal issues related to the use of laboratory animals. In 2014, CONCEA put together a framework for expanding the implementation of non-animal methodologies for use in research and education. It also promoted the regulatory acceptance in Brazil of 24 test guidelines, including 15 in vitro approaches. It should be emphasised that, in Brazilian legislation, replacement is generally based on the toxicological endpoint and not on the category of product, as tends to be the case in other countries (e.g. cosmetics in the European Union). The resolution-dependent deadlines for the obligatory replacement of in vivo methods with the CONCEA-approved tests are 2019 and 2021. Brazil has advanced considerably towards the replacement of animal experimentation, and in certain aspects, this has been in a highly progressive manner. However, there is still a lot of work to be done, especially considering the current political scenario with reduced investment in research, development and innovation. The chronology of significant events following the approval of the Arouca Law, which have contributed to the promotion of the Three Rs alternatives in Brazil, will be examined.


Assuntos
Experimentação Animal , Alternativas aos Testes com Animais , Alternativas aos Testes com Animais/tendências , Animais , Animais de Laboratório , Brasil , Projetos de Pesquisa
13.
Altern Lab Anim ; 47(5-6): 196-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32090616

RESUMO

Few attempts have been made to estimate the global use of animals in experiments, since our own estimated figure of 115.2 million animals for the year 2005. Here, we provide an update for the year 2015. Data from 37 countries that publish national statistics were standardised against the definitions of 'animals' and 'procedures' used in the European Union (EU) Directive 2010/63/EU. We also applied a prediction model, based on publication rates, to estimate animal use in a further 142 countries. This yielded an overall estimate of global animal use in scientific procedures of 79.9 million animals, a 36.9% increase on the equivalent estimated figure for 2005, of 58.3 million animals. We further extrapolated this estimate to obtain a more comprehensive final global figure for the number of animals used for scientific purposes in 2015, of 192.1 million. This figure included animals killed for their tissues, normal and genetically modified (GM) animals without a harmful genetic mutation that are used to maintain GM strains and animals bred for laboratory use but not used. Since the 2005 study, there has been no evident increase in the number of countries publishing data on the numbers of animals used in experiments. Without regular, accurate statistics, the impact of efforts to replace, reduce and refine animal experiments cannot be effectively monitored.


Assuntos
Experimentação Animal , Animais de Laboratório , Experimentação Animal/estatística & dados numéricos , Alternativas aos Testes com Animais/estatística & dados numéricos , Alternativas aos Testes com Animais/tendências , Animais , União Europeia
14.
Toxicol Sci ; 167(1): 6-14, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496580

RESUMO

The National Toxicology Program (NTP) receives requests to evaluate chemicals with potential to cause adverse health effects, including developmental neurotoxicity (DNT). Some recent requests have included classes of chemicals such as flame retardants, polycyclic aromatic compounds, perfluoroalkyl substances, and bisphenol A analogs with approximately 20-50 compounds per class, many of which include commercial mixtures. However, all the compounds within a class cannot be tested using traditional DNT animal testing guideline studies due to resource and time limitations. Hence, a rapid and biologically relevant screening approach is required to prioritize compounds for further in vivo testing. Because neurodevelopment is a complex process involving multiple distinct cellular processes, one assay will unlikely address the complexity. Hence, the NTP sought to characterize a battery of in vitro and alternative animal assays to quantify chemical effects on a variety of neurodevelopmental processes. A culmination of this effort resulted in a NTP-hosted collaborative project with approximately 40 participants spanning across domains of academia, industry, government, and regulatory agencies; collaborators presented data on cell-based assays and alternative animal models that was generated using a targeted set of compounds provided by the NTP. The NTP analyzed the assay results using benchmark concentration (BMC) modeling to be able to compare results across the divergent assays. The results were shared with the contributing researchers on a private web application during the workshop, and are now publicly available. This article highlights the overview and goals of the project, and describes the NTP's approach in creating the chemical library, development of NTPs data analysis strategy, and the structure of the web application. Finally, we discuss key issues with emphasis on the utility of this approach, and knowledge gaps that need to be addressed for its use in regulatory decision making.


Assuntos
Alternativas aos Testes com Animais/métodos , Poluentes Ambientais/classificação , Poluentes Ambientais/toxicidade , Programas Governamentais , Síndromes Neurotóxicas/etiologia , Toxicologia , Alternativas aos Testes com Animais/tendências , Animais , Guias como Assunto , Desenvolvimento de Programas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/toxicidade , Testes de Toxicidade , Toxicologia/métodos , Toxicologia/tendências , Estados Unidos
15.
Toxicol Mech Methods ; 28(5): 369-385, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29297242

RESUMO

The liver is a vital organ fulfilling a central role in over 500 major metabolic functions, including serving as the most essential site for drug biotransformation. Dysfunction of the drug biotransformation processes may result in the exposure of the liver (and other organs) to hepatotoxins, potentially interacting with cellular constituents and causing toxicity and various lesions. Hepatotoxicity can be investigated on a tissue, cellular and molecular level by employing various in vivo and in vitro techniques, including novel three-dimensional (3 D) cell culturing methods. This paper reflects on the liver and its myriad of functions and the influence of drug biotransformation on liver dysfunction. Current in vivo and in vitro models used to study liver function and dysfunction is outlined, emphasizing their advantages and disadvantages. The advantages of novel in vitro 3 D cell culture models are discussed and the possibility of novel models to bridge the gap between in vitro and in vivo models is explained. Progression made in the field of cell culturing methods such as 3 D cell culturing techniques over the last decade promises to reduce the use of in vivo animal models in biotransformation and toxicological studies of the liver.


Assuntos
Técnicas de Cultura de Células/tendências , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Descoberta de Drogas/tendências , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Testes de Toxicidade/tendências , Alternativas aos Testes com Animais/tendências , Animais , Biotransformação , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Difusão de Inovações , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Medição de Risco , Especificidade da Espécie
16.
Toxicol Sci ; 161(2): 285-289, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29267930

RESUMO

Toxicology uniquely among the life sciences relies largely on methods which are more than 40-years old. Over the last 3 decades with more or less success some additions to and few replacements in this toolbox took place, mainly as alternatives to animal testing. The acceptance of such new approaches faces the needs of formal validation and the conservative attitude toward change in safety assessments. Only recently, there is growing awareness that the same alternative methods, especially in silico and in vitro tools can also much earlier and before validation inform decision-taking in the product life cycle. As similar thoughts developed in the context of Green Chemistry, the term of Green Toxicology was coined to describe this change in approach. Here, the current developments in the alternative field, especially computational and more organo-typic cell cultures are reviewed, as they lend themselves to front-loaded chemical safety assessments. The initiatives of the Center for Alternatives to Animal Testing Green Toxicology Collaboration are presented. They aim first of all for forming a community to promote this concept and then for a cultural change in companies with the necessary training of chemists, product stewards and later regulators.


Assuntos
Alternativas aos Testes com Animais/métodos , Segurança Química/métodos , Química Verde/métodos , Toxicologia/métodos , Alternativas aos Testes com Animais/tendências , Animais , Segurança Química/normas , Química Verde/tendências , Humanos , Testes de Toxicidade , Toxicologia/tendências
17.
Transfus Clin Biol ; 24(3): 93-95, 2017 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28669523

RESUMO

Animal experiment is a subject of controversies. Some people, defenders of animals, think that it is not acceptable to use for scientific purposes at the risk of making them suffer or assert that the results obtained with animals are not transposable in the human beings. Others, in particular researchers in biology or medicine, think that the animal models are essential for the biomedical search. This confrontation of the opinions bases largely on an evolution of the place of animals in our society. The regulations authorize the use of animals for scientific purposes but oblige to make it under restrictive conditions. The application of 3Rs - replacement, reduction, and refinement - expressed in 1959 by Russel and Burch is an ethical guide to improve the welfare of animals in research. The alternative methods do not allow, in the present state of the knowledge, to answer all the scientific questions in biology and medicine research. They are, most of the time, complementary methods of the in vivo methods.


Assuntos
Alternativas aos Testes com Animais , Experimentação Animal/ética , Experimentação Animal/legislação & jurisprudência , Alternativas aos Testes com Animais/ética , Alternativas aos Testes com Animais/legislação & jurisprudência , Alternativas aos Testes com Animais/métodos , Alternativas aos Testes com Animais/tendências , Animais , França
18.
ALTEX ; 34(4): 479-500, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28539002

RESUMO

Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them. Bringing about change will require a paradigm shift in current approaches to testing - and a concerted effort to generate better data on risks to human health from exposure to leachable chemicals from medical devices, and to boost confidence in the use of alternative methods to test devices. To help advance these ideas, stir debate about best practices, and coalesce around a roadmap forward, the JHU-Center for Alternatives to Animal Testing (CAAT) hosted a symposium believed to be the first gathering dedicated to the topic of in vitro testing of medical devices. Industry representatives, academics, and regulators in attendance presented evidence to support the unique strengths and challenges associated with the approaches currently in use as well as new methods under development, and drew next steps to push the field forward from their presentations and discussion.


Assuntos
Alternativas aos Testes com Animais/tendências , Equipamentos e Provisões/normas , Técnicas In Vitro , Testes de Toxicidade , Animais , Humanos , Pesquisa
19.
Arch Toxicol ; 91(1): 1-33, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27492622

RESUMO

Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells. They differ in their read-outs and range from simple viability assays to complex functional endpoints such as neural crest cell migration. Monitoring of toxicological effects on differentiation often requires multiomics approaches, while the acute disturbance of neuronal functions may be analysed by assessing electrophysiological features. Extrapolation from in vitro data to humans requires a deep understanding of the test system biology, of the endpoints used, and of the applicability domains of the tests. Moreover, it is important that these be combined in the right way to assess toxicity. Therefore, knowledge on the advantages and disadvantages of all cellular platforms, endpoints, and analytical methods is essential when establishing in vitro test systems for different aspects of neurotoxicity. The elements of a test, and their evaluation, are discussed here in the context of comprehensive prediction of potential hazardous effects of a compound. We summarize the main cellular characteristics underlying neurotoxicity, present an overview of cellular platforms and read-out combinations assessing distinct parts of acute and developmental neurotoxicology, and highlight especially the use of stem cell-based test systems to close gaps in the available battery of tests.


Assuntos
Modelos Biológicos , Mutagênicos/toxicidade , Neurônios/efeitos dos fármacos , Neurotoxinas/toxicidade , Teratogênicos/toxicidade , Toxicologia/métodos , Alternativas aos Testes com Animais/tendências , Animais , Automação Laboratorial , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Células Cultivadas , Guias como Assunto , Ensaios de Triagem em Larga Escala/normas , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutagênicos/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neurotoxinas/metabolismo , Medição de Risco/tendências , Teratogênicos/metabolismo , Testes de Toxicidade Aguda/normas , Toxicocinética , Toxicologia/tendências
20.
Arch Toxicol ; 91(1): 131-142, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27766365

RESUMO

Drug-induced liver injury (DILI) is a major concern for drug developers, regulators and clinicians. It is triggered by drug and xenobiotic insults leading to liver impairment or damage, in the worst-case liver failure. In contrast to acute "intrinsic" hepatotoxicity, DILI typically manifests in a very small subset of the population under treatment with no clear dose relationship and inconsistent temporal patterns and is therefore termed an idiosyncratic event. Involved are multifactorial, compound-dependent mechanisms and host-specific factors, making the prediction in preclinical test systems very challenging. While preclinical safety studies in animals usually are able to capture direct, acute liver toxicities, they are less predictive for human DILI, where specific, human-derived in vitro models can potentially close the gap. On one hand, mechanistic approaches addressing key mechanisms involved in DILI in well-characterized and standardized in vitro test systems have been developed. On the other hand, co-cultures of different cell types, including patient- and/or stem cell-derived cells, in a three-dimensional setup allow for prolonged incubations and multiplexed readouts. Such complex setups might better reflect multifactorial human DILI. One major challenge is that for many compounds with human DILI the underlying mechanisms are not yet fully understood, complicating establishment and validation of predictive cellular tools. A tiered approach including rapid mechanism-based in vitro screens followed by confirmatory tests in more physiologically relevant models might allow minimizing DILI risk early on in vitro. Such complex, integrated approaches will gain from larger collaborations in multidisciplinary groups bringing existing knowledge and state-of-the-art technology together.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Avaliação Pré-Clínica de Medicamentos , Drogas em Investigação/efeitos adversos , Modelos Biológicos , Xenobióticos/toxicidade , Alternativas aos Testes com Animais/tendências , Animais , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Biologia Computacional , Avaliação Pré-Clínica de Medicamentos/tendências , Drogas em Investigação/metabolismo , Sistemas Inteligentes , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Reconhecimento Automatizado de Padrão/tendências , Reprodutibilidade dos Testes , Pesquisa Translacional Biomédica/tendências , Xenobióticos/metabolismo
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