Development of an <i>In Vitro</i> Test Battery for the Estimation of Acute Human Systemic Toxicity: An Outline of the EDIT Project

Clemedson, Cecilia; Nordin-Andersson, Marika; Bjerregaard, Henning F.; Clausen, J.; Forsby, Anna; Gustafsson, Helena; Hansson, Ulrika; Isomaa, Boris; Jørgensen, Claus; Kolman, Ada; Kotova, Natalia; Krause, Günter; Kristen, U.; Kurppa, Kalle; Romert, Lennart; Scheers, Ellen

doi:10.1177/026119290203000309

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…5 Another reason that correlations between in vitro and in vivo data contain outliers is related to the tendency for the actual concentrations in in vitro tests to be much lower than the nominal concentrations. The MEIC study 8 clearly indicated that the basal cytotoxicity test should be complemented by in vitro tests for kinetics and organ-specific toxicity so as to improve the predictability. In ACuteTox, a set of rules or alerts has been developed to identify chemicals for which at least one of these processes may result in a reduced concentration.…”

Section: The Need For New In Vitro Testing Strategies For Estimating mentioning

confidence: 99%

“…From the results of previous studies it has been estimated that if IC 50 values for basal cell cytotoxicity are used for classification purposes, the data for about 30% of chemicals would result in either underestimation or overestimation of the LD 50 values. The MEIC study 8 clearly indicated that the basal cytotoxicity test should be complemented by in vitro tests for kinetics and organ-specific toxicity so as to improve the predictability. Thus, in ACuteTox existing outliers of the in vitro-in vivo correlation are evaluated in order to introduce further parameters, such as administration, distribution, and elimination (ADE), metabolism, and organ specificity, which might improve the correlation.…”

Section: The Need For New In Vitro Testing Strategies For Estimating mentioning

confidence: 99%

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The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

Clemedson¹

2008

Clin Pharmacol Ther

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ACuteTox (optimization and prevalidation of an in vitro test strategy for predicting human acute toxicity) is an integrated European Union project under the Sixth Framework Programme with the aim of demonstrating that animal tests for acute systemic toxicity currently used for regulatory purposes could be replaced by a combination of alternative assays. Validated alternative test methods are urgently required for safety toxicology testing of chemicals, cosmetics, and drugs.

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Section: The Need For New In Vitro Testing Strategies For Estimating mentioning

confidence: 99%

Section: The Need For New In Vitro Testing Strategies For Estimating mentioning

confidence: 99%

The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

Clemedson¹

2008

Clin Pharmacol Ther

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“…Since the initiation of the MEIC study, it has been recognised that the predictivity of basal cytotoxicity assays for acute toxicity could be improved by various means, in particular, by including in vitro methods for biotransformation, absorption in the gut, passage across the blood-brain barrier, distribution volumes, protein binding, and renal clearance/accumulation in a test battery, as well as models for target organ toxicity, in conjunction with tests for neurotoxic potential (199). Clearly, such extra parameters in the testing battery should also take account of the use of human cells (200).…”

Section: Acute Toxicity Testingmentioning

confidence: 99%

Metabolism: A Bottleneck in In Vitro Toxicological Test Development

et al. 2006

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This is the 54th report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main objective of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences, and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and of opportunities for the possible incorporation of alternative methods into regulatory procedures. It was decided that this would be best achieved through a programme of ECVAM workshops, each addressing a specific topic, and at which selected groups of independent international experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward.A workshop on Metabolism: a bottleneck in in vitro toxicological test development, was held at

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“…This work continues in the Evaluation-guided Development of New In vitro Test Batteries (EDIT) programme. Together with toxicokinetic modelling tools, this test battery is anticipated to work as well, if not better than, the rodent in vivo tests for prediction of the acute toxicities of chemicals (5,6). Due to the importance of these basic data, for example, in the classification and labelling of chemicals and also because the in vivo tests can be very painful, their replacement with in vitro testing is important.…”

Section: Status Of the Development Of The In Vitro Test Guidelinesmentioning

confidence: 99%

Status and Prospects of In Vitro Tests in Risk Assessment

Louekari

2004

Altern Lab Anim

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According to the new chemicals policy of the European Union (EU), most chemicals, i.e. the 20,000 chemicals manufactured or imported at 1–10 tons annually, should be tested primarily by using in vitro methods. Also, for other chemicals, the use of in vitro methods is encouraged in the testing strategies given in the draft EU legislation. However, the validation and international acceptance of in vitro tests has been slow. Only recently has the OECD approved four new in vitro test methods, validated by the European Centre for the Validation of Alternative Methods. An analysis of ten randomly selected risk assessment reports of the EU Existing Chemicals Risk Assessment Programme showed that in vitro studies, for example, on cytotoxicity to different cell cultures, cell transformation, metabolism and skin penetration (a total of 115 studies) were used for the assessments. Key metabolic pathways and mechanisms of toxicity have been elucidated, for some chemicals, by using in vitro methods. On the other hand, the results of in vitro studies were regarded as secondary or unreliable in some cases. For several toxic endpoints, in vitro methods will probably serve as screening tools and for mechanistic studies, while target organ toxicity or physiologically regulated adverse effects caused by long-term exposure are difficult to observe without the use of animal models.

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Development of an In Vitro Test Battery for the Estimation of Acute Human Systemic Toxicity: An Outline of the EDIT Project

Cited by 21 publications

References 36 publications

The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

Metabolism: A Bottleneck in In Vitro Toxicological Test Development

Status and Prospects of In Vitro Tests in Risk Assessment

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