Progress in the Development, Validation and Regulatory Acceptance of In Vitro Methods for Toxicity Testing

This review focuses on the use of replacement in vitro tissue culture methods for regulatory safety assessment in response to REACH and the 7 th Amendment to the EU Cosmetics Directive, international criteria for test validation, and the application of new technologies, particularly for miniaturization and high throughput screening. The current situation regarding test development, validation status, and regulatory acceptance is described for each of the major toxicity endpoints required for regulatory hazard assessment. The use of integrated tier-testing batteries and key issues, including human cells, stem cells and complex three-dimensional cultures, are discussed. Lastly, barriers to, and prospects for, improvements to test methods, and the development of new assays, are considered.