Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat

- Historically, satellite groups are used for rodent TK profiling.
- Vehicle dosed Wistar rats were un-sampled, conventional blood volume, or μ-sampled.
- Terminal clinical pathology parameters were within the historical background range.
- Statistically significant haematological changes in conventionally sampled rats.
- μ-Sampling of adult rats is possible without adverse toxicological consequences.

Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups.MethodsGroups of 10 male (200-300 g) and female (150-250 g) rats aged 10 weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6 × 200 μL) or microsampled (6 × 32 μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained.ResultsAll clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p < 0.001) decrease in haemaglobin, haematocrit and red blood cell count, an increase in reticulocytes (at least p < 0.01), increased AST and GLDH and, in males only, an increase in monocytes and neutrophils. In contrast, microsampled animals showed no changes except for a slight, toxicologically insignificant decrease in haemoglobin concentration (15.0 g/dL compared to the unsampled group mean of 14.4 g/dL) in females (p < 0.05) and a small increase in monocytes (p < 0.05) in males.ConclusionMicrosampling of adult rats is possible without adverse toxicological consequences.