title: Strategies for the optimisation of in vivo experiments in accordance with the 3Rs philosophy.
abstract: There are a large number of chemicals in current use for which adequate toxicity data are not available. Whilst there are clear ethical and legal obligations to obtain data from sources other than in vivo experiments wherever possible, in certain cases in vivo assays may be deemed necessary. In such circumstances, it is essential to ensure that the maximum amount of high quality data is obtained from the minimum number of animals, using the most humane procedures, in accordance with the philosophy of reduction, refinement and replacement (3Rs). The aim of this report is to provide a strategy for anyone involved in animal experimentation, for either toxicological or pharmacological purposes, as to how in vivo experiments may be optimised. The impact of generic and endpoint specific sources of variability has been highlighted in a proof-of-principle analysis considering the variation in protocols for assays for four human health endpoints (skin sensitisation, reproductive/developmental toxicity, mutagenicity and carcinogenicity). Other factors such as operator training, experimental/statistical design, use of lower species and use of combined assays are also discussed. Recommendations for optimisation of in vivo assays, in terms of the 3Rs philosophy, applied to performing tests, harvesting data and appropriate reporting are summarised as a checklist of issues to be addressed prior to undertaking such assays.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, England, UK. j.madden@ljmu.ac.uk
authors.forename: Judith C
authors.initials: JC
authors.lastname: Madden
authors.forename: Mark
authors.initials: M
authors.lastname: Hewitt
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Przybylak
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*