Powles-Glover Nicola, Kirk Sarah, Jardine Lynne, Clubb Stephanie, Stewart Jane
Astrazeneca, Mereside, Alderley Park, Alderley Edge SK10 4TG, UK.
Astrazeneca, Mereside, Alderley Park, Alderley Edge SK10 4TG, UK.
Regul Toxicol Pharmacol. 2014 Aug;69(3):425-33. doi: 10.1016/j.yrtph.2014.05.006. Epub 2014 May 19.
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.
Microsamples 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.
Suckling 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.
The 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.
幼鼠尾静脉微量采血用于毒代动力学评估有显著减少卫星动物使用的潜力。本文探讨了在不同出生后天数(PND)进行微量采血的毒理学后果。
微量样本采集如下:哺乳幼崽,每组10只/性别,在PND19采集3次,每次32μL样本,于PND20处安乐死;断奶幼崽,每组10只/性别,在PND23和PND37各采集6次,每次32μL样本,于PND38处安乐死;卫星幼崽,每组3只/性别,在PND14和PND35各采集5次,每次32μL样本,于PND36处安乐死。在PND20或PND38处死时,采集临床病理学样本并检查脾脏、肝脏和骨髓。每个实验有10只未采血的同期对照动物。
哺乳动物:雌性红细胞计数略有统计学显著下降(为对照组的0.94倍;p<0.05),血红蛋白和血细胞比容略有下降。哺乳雄性网织红细胞计数略有增加(为对照组的1.05倍),相对脾脏重量有统计学显著的轻微增加。断奶动物:唯一的影响是微量采血的雌性肝脏重量下降。在哺乳和断奶实验中,所有临床病理学值均在年龄对照范围内。在PND14进行微量采血的卫星幼崽中,PND17至PND21期间体重增加有统计学显著的短暂增加。
微量采血的毒理学效应性质符合预期。只要在研究设计和失血量方面加以注意,效应的程度并不排除对主要测试幼崽进行微量采血。