Toxicity testing: The search for an in vitro alternative to animal testing

Xu, Jinsheng; Morse, Ruth; May, Jennifer E.; Donaldson, Craig; Avent, N. D.

Abstract

Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

• Journal Article Type: Review
• Publication Date: Jan 1, 2009
• Deposit Date: Sep 23, 2010
• Publicly Available Date: Mar 31, 2016
• Journal: British Journal of Biomedical Science
• Print ISSN: 0967-4845
• Peer Reviewed: Peer Reviewed
• Volume: 66
• Issue: 3
• Pages: 160-165
• DOI: https://doi.org/10.1080/09674845.2009.11730265
• Keywords: animal testing alternatives, Cytochrome P-450 enzyme system,; drug toxicity, prodrugs
• Public URL: https://uwe-repository.worktribe.com/output/1004201
• Publisher URL: http://dx.doi.org/10.1080/09674845.2009.11730265
• Additional Information: Additional Information : May, Jennifer E. and Xu, Jinsheng and Morse, Ruth and Avent, N.D. and Donaldson, Craig (2009) Toxicity testing: The search for an in vitro alternative to animal testing. British Journal of Biomedical Science, 66 (3). pp. 160-165. ISSN 0967-4845. This is the final draft, after peer-review, of a manuscript published in the British Journal of Biomedical Science. The definitive version, detailed above, is available online at http://dx.doi.org/10.1080/09674845.2009.11730265
• Contract Date: Mar 31, 2016