Strategies For Reducing The Number Of Animals In Toxicity Testing: A Comparative Approach For Rodent And Large Animal Studies

By Narine Lalayeva, Julie Forget, and Norbert Makori

It is crucial for the scientific community to continuously reassess study designs and technologies that reduce the number of subjects used in toxicology studies, in alignment with the 3Rs of experimental animal welfare (Replacement, Reduction, and Refinement). In rodent studies, we implemented blood microsampling as a refinement over the traditional needle and syringe method, using the Mitra™ Volumetric Absorptive MicroSampling (VAMS®) device for accurate, low-volume blood collection. By microsampling just 10 μL of whole blood, we eliminated the need for an entire cohort of animals, allowing serial samples to be collected from the main study subjects.

This change resulted in a 55% reduction in mouse studies and a 100% reduction in rat studies. Using samples from the same cohort also enables correlations between pharmacodynamic findings and the actual drug exposure profile. In nonhuman primates (NHPs) and dogs, we analyzed control and recovery cohort numbers in chronic studies with prior subacute data, leading to a >25% reduction in control groups without a recovery cohort, including in low-dose groups.

This NHP study design was reviewed and approved by a regulatory agency. These strategies will be discussed further to highlight their pros and cons, allowing for more informed decisions in toxicity study design.