ECITTS: An Integrated Approach to the Application of In Vitro Test Systems to the Hazard Assessment of Chemicals,

As a result of a workshop held at Täljöviken, Åkersberga, Sweden, on 27–29 May 1991, a multicentre collaborative research project was established, with the purpose of developing the concept of integrated in vitro toxicity testing. The first priority was the selection of tests within eight appropriate areas: basal cytotoxicity, irritancy, developmental toxicity, hepatotoxicity, nephrotoxicity, immunotoxicity, neurotoxicity and biokinetics. An ideal battery of tests for each area was identified. Since it was realised that it would not be feasible to include the full ideal list of tests in the project, a minimum test list was also agreed. For each area, ten calibration chemicals were selected. From these 80 compounds, 30 were selected for inclusion, together with 20 of the OECD test programme chemicals, in a first test set of chemicals. The toxicity of these 50 test set chemicals will be investigated in the minimum integrated test scheme. The aim of the project is to employ non-animal methods to assess the toxicological properties of chemicals, and to improve this assessment through the use of knowledge about mechanisms of toxic action. The information produced will contribute to the establishment of a more-scientific and more-efficient toxicological procedure for hazard assessment. Questions concerning which parameters need to be investigated and combined to make hazard assessments, and which parameters relevant to in vivo toxicity can be determined in non-whole animal test systems, will also be addressed.

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In Vitro Toxicology Methods in Risk Assessment

Alternatives to Laboratory Animals ◽

10.1177/026119299602400305 ◽

1996 ◽

Vol 24 (3) ◽

pp. 325-331

Author(s):

Iain F. H. Purchase

Keyword(s):

Risk Assessment ◽

Hazard Assessment ◽

Human Health Risk ◽

In Vitro Test ◽

In Vitro Methods ◽

New Concepts ◽

Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

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Spirulina, Palmaria Palmata, Cichorium Intybus, and Medicago Sativa extracts in cosmetic formulations: an integrated approach of in vitro toxicity and in vivo acceptability studies

Cutaneous and Ocular Toxicology ◽

10.1080/15569527.2019.1579224 ◽

2019 ◽

Vol 38 (4) ◽

pp. 322-329 ◽

Cited By ~ 3

Author(s):

Patrícia M. B. G. Maia Campos ◽

Carolina G. Benevenuto ◽

Lívia S. Calixto ◽

Maísa. O. Melo ◽

Karina C. Pereira ◽

...

Keyword(s):

Medicago Sativa ◽

Integrated Approach ◽

Cichorium Intybus ◽

Palmaria Palmata ◽

In Vitro Toxicity ◽

Cosmetic Formulations

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Integrative Strategy of Testing Systems for Identification of Endocrine Disruptors Inducing Metabolic Disorders—An Introduction to the OBERON Project

International Journal of Molecular Sciences ◽

10.3390/ijms21082988 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2988 ◽

Cited By ~ 2

Author(s):

Karine Audouze ◽

Denis Sarigiannis ◽

Paloma Alonso-Magdalena ◽

Celine Brochot ◽

Maribel Casas ◽

...

Keyword(s):

Endocrine Disruptors ◽

Metabolic Disorders ◽

Computational Models ◽

Human Biomonitoring ◽

Integrated Approach ◽

The European Union ◽

Joint Research ◽

Test Systems

Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect ED-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine (1) experimental methods (in vitro, e.g., using 2D and 3D human-derived cells and tissues, and in vivo, i.e., using zebrafish at different stages), (2) high throughput omics technologies, (3) epidemiology and human biomonitoring studies and (4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such interdisciplinary framework will help in deciphering EDs based on a mechanistic understanding of toxicity by providing and making available more effective alternative test methods relevant for human health that are in line with regulatory needs. Data generated in OBERON will also allow the development of novel adverse outcome pathways (AOPs). The assays will be pre-validated in order to select the test systems that will show acceptable performance in terms of relevance for the second step of the validation process, i.e., the inter-laboratory validation as ring tests. Therefore, the aim of the OBERON project is to support the organization for economic co-operation and development (OECD) conceptual framework for testing and assessment of single and/or mixture of EDs by developing specific assays not covered by the current tests, and to propose an IATA for ED-related metabolic disorder detection, which will be submitted to the Joint Research Center (JRC) and OECD community.

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In Vitro Toxicity Testing: Purpose, Validation and Strategy

Alternatives to Laboratory Animals ◽

10.1177/026119299001800103.1 ◽

1990 ◽

Vol 18 (1_part_1) ◽

pp. 11-18 ◽

Cited By ~ 1

Author(s):

Oliver P. Flint

Keyword(s):

Cell Function ◽

Toxicity Testing ◽

In Vitro Toxicity ◽

In Vitro Tests ◽

In Vitro Test ◽

Vitro Test ◽

Basal Cytotoxicity ◽

Biological Endpoint

The fullest potential for in vitro evaluation of toxicity will be realised in the context of the process of assessing the risk of human toxicity. This article is an attempt to clarify what contributions can be made by in vitro tests and what types of in vitro test can best be used. In vitro tests are clarified according to the type of biological endpoint evaluated, first into tests for general (‘basal’) cytotoxicity and, secondly, into tests for differentiated cell function. The role of each type of test is analysed and it is suggested that tests for general cytotoxicity, as opposed to differentiated function, are difficult to interpret in terms of in vivo toxicity. A general approach to evaluating in vitro tests is described, and a strategy for using these tests is proposed.

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