Assessment of haematological and clinical pathology effects of blood microsampling in suckling and weaned juvenile rats

Abstract

Tail vein microsampling in juvenile rats for toxicokinetic assessment has the potential to significantly reduce satellite animal use. This paper explores the toxicological consequences of microsampling at various post natal day (PND) ages. MethodsMicrosamples were taken as follows: suckling pups, 10 pups/sex, 3×32μL samples on PND19, euthanased PND20; weaned pups, 10 pups/sex, 6×32μL samples on PND23 and PND37, euthanased PND38; and satellite pups, 3 pups/sex, 5×32μL samples on PND14 and PND35, euthanased on PND36. At termination on PND20 or PND38, clinical pathology samples were obtained and spleen, liver and bone marrow were examined. There were 10 unsampled concurrent control animals for each experiment. ResultsSuckling animals: females showed a slight, statistically significant decrease in red blood cell count (0.94× of control; p<0.05) with slight decreases in haemoglobin and haematocrit. The suckling males showed a slight increase in reticulocyte counts (1.05× of control) plus a statistically significant, slight increase in relative splenic weight. Weanling animals: the only effect was decreased liver weight in the microsampled females. In both suckling and weanling experiments, all clinical pathology values were within the age control range. In the satellite pups microsampled on PND14, there was a statistically significant transient increase in bodyweight gain between PND17 and PND21. ConclusionThe nature of the toxicological effects of microsampling was as expected. The magnitude of effects does not preclude microsampling main test pups provided care is taken over study design and blood volume loss.