Proposed Best Practices For Optimizing The Number Of Animals In Toxicology Studies

By Narine Lalayeva, Julie Forget, and Norbert Makori

The emergence of new drug modalities, coupled with the limited availability of certain research animal models, underscores the need for continuous evaluation of study designs and technologies that support the reduction of animal use in toxicology studies—an approach that aligns with the 3Rs of experimental animal welfare. In rodents, blood microsampling offers a refined alternative to traditional needle and syringe collection by enabling precise low-volume sampling. By collecting just 10 μL of whole blood, an entire cohort of animals was eliminated from studies, leading to a 55% reduction in mouse study animals and a complete elimination of extra rat cohorts.

This approach also allows for serial sampling within the same cohort, facilitating direct correlations between pharmacodynamic findings and drug exposure profiles. In nonhuman primates (NHPs) and dogs, a review of chronic study designs incorporating prior subacute study data enabled a >25% reduction in control groups, eliminating the need for a recovery cohort in low-dose groups. Notably, this revised NHP study design was reviewed and accepted by a regulatory agency. Each of these strategies will be further explored, highlighting their advantages and limitations to guide more informed decisions in toxicity study design.