Applying the 3Rs to urinalysis assessments in toxicity studies: refining procedures and adopting a case-by-case approach

Urinalysis is routinely performed in toxicology studies, for both regulatory and non-regulatory purposes, in species such as rats, dogs, minipigs and non-human primates. Sample collection usually requires animals to be individually housed in a metabolism cage and/or catheterised, raising animal welfare considerations. It is not clear if urinalysis results are being used as part of safety evaluation and how often they play a role in decision-making, as the quality of the data can be highly variable, and there are other assessments (e.g. kidney histopathology) that may provide more detailed and better-qualified information. This article summarises presentations and case studies from a workshop co-organised by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the Association for Comparative Clinical Pathology (ACCP) in October 2023, discussing the value of urinalysis within pharmaceutical and agrochemical product development and opportunities for refinement. These include performing urinalysis on a case-by-case basis rather than in every repeat-dose toxicology study, using a single species when appropriate and minimising the duration of urine collection periods and single housing. A first step for this 3Rs opportunity would be to collect evidence on the value of urinalysis assessment in toxicology studies and its impact on decision-making, through a data-sharing project highlighting case studies where urinalysis could have been avoided without changing the study outcome.