Acute Toxicity Testing in Vitro and the Classification and Labelling of Chemicals

Seibert, Hasso; Balls, Michael; Fentem, Julia H.; Bianchi, Vera; Clothier, Richard H.; Dierickx, Paul J.; Ekwall, Björn; Garle, Michael J.; Gómez‐Lechón, M. José; Gribaldo, Laura; Gülden, Michael; Leibsch, M.; Rasmussen, Eva; Roguet, R.; Shrivastava, Ravi; Walum, Erik

doi:10.1177/026119299602400409

Cited by 33 publications

(24 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The idea that in vitro cytotoxicity data could be used to determine the starting doses for rodent acute oral toxicity tests (and consequently reduce the number of animals used) was first discussed at a workshop organized to evaluate the use of in vitro data for the classification and labeling of chemicals (Seibert et al, ). The concept was later discussed and evaluated, along with a number of other international initiatives at the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity (ICCVAM, ).…”

Section: Commentarymentioning

confidence: 99%

Neutral Red Uptake Cytotoxicity Tests for Estimating Starting Doses for Acute Oral Toxicity Tests

Stokes

Casati²,

Strickland

et al. 2008

CP Toxicology

View full text Add to dashboard Cite

In vitro cytotoxicity assays can be used as alternative toxicity tests to reduce the total number of animals needed for acute oral toxicity tests. This unit describes two methods for determining the in vitro cytotoxicity of test substances using neutral red uptake (NRU) and using the in vitro data to determine starting doses for in vivo acute oral systemic toxicity tests, e.g., the up-and-down procedure or the acute toxic class method. The use of the NRU methods to determine starting doses for acute oral toxicity tests may reduce the number of animals required, and for relatively toxic substances, this approach may also reduce the number of animals that die or require humane euthanasia due to severe toxicity. An interlaboratory validation study has demonstrated that the methods are useful and reproducible for these purposes. Two standardized protocols provide details for performing NRU tests with rodent and human cells.

show abstract

Section: Commentarymentioning

confidence: 99%

Neutral Red Uptake Cytotoxicity Tests for Estimating Starting Doses for Acute Oral Toxicity Tests

Stokes

Casati²,

Strickland

et al. 2008

CP Toxicology

View full text Add to dashboard Cite

show abstract

“…By using this strategy, a test substance is classified as either very toxic, toxic or harmful, depending on which order of testing provides a positive outcome. This scheme, with the additional use of biokinetic information at each stage, is essentially the same as the one recommended by ECVAM and presented by Seibert et al (57).…”

Section: Previous Testing Strategiesmentioning

confidence: 98%

Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation

et al. 2008

View full text Add to dashboard Cite

Liverpool John Moores University and FRAME conducted a joint research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

show abstract

“…We were also together at one of the most important workshops, on Acute toxicity testing in vitro and the classification and labelling of chemicals (12). This workshop brought together the ideas of Björn and ERGATT, and the main elements of the MEIC Programme and ECITTS.…”

Section: Erik Walum and Ecvammentioning

confidence: 99%

Scandinavia and the Replacement of in Vivo Toxicity Tests: Some Personal Reflections

Balls

2015

Altern Lab Anim

Self Cite

View full text Add to dashboard Cite

A personal, and therefore unavoidably biased, review is given, of the significance of the contributions made by selected Scandinavian individuals, organisations and events, to the development of in vitro toxicology procedures as potential replacements for toxicity tests in laboratory animals. In addition to their wider significance, these contributions had a profound effect on whatever contributions I have been able to make, myself. Nevertheless, while there has been much progress in the last 35 years or so, and many lessons have been learned, there is still much to be done, especially as animal tests remain entrenched as the preferred methods which set the gold standards and make regulators feel comfortable. Many of the clues to dealing with the questions and concerns which plague hazard prediction and risk assessment have long been available, but they have been ignored, largely for reasons which have little to do with the science of toxicology and the need to maintain the highest scientific standards. I have little doubt that Björn Ekwall, whose memory I feel privileged to honour, would have agreed with that last statement.

show abstract

Acute Toxicity Testing in Vitro and the Classification and Labelling of Chemicals

Cited by 33 publications

References 21 publications

Neutral Red Uptake Cytotoxicity Tests for Estimating Starting Doses for Acute Oral Toxicity Tests

Neutral Red Uptake Cytotoxicity Tests for Estimating Starting Doses for Acute Oral Toxicity Tests

Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation

Scandinavia and the Replacement of in Vivo Toxicity Tests: Some Personal Reflections

Contact Info

Product

Resources

About