title: Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat.
abstract: 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.
  
  
  METHODS
  Groups of 10 male (200-300g) and female (150-250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200μL) or microsampled (6×32μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained.
  
  
  RESULTS
  All 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 (15.0g/dL compared to the unsampled group mean of 14.4g/dL) in females (p<0.05) and a small increase in monocytes (p<0.05) in males.
  
  
  CONCLUSIONS
  Microsampling of adult rats is possible without adverse toxicological consequences.
authors.affiliation: AstraZeneca, Innovative Medicines, Drug Safety Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom. Electronic address: Nicola.powlesglover@astrazeneca.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Powles-Glover
authors.affiliation: AstraZeneca, Innovative Medicines, Drug Safety Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kirk
authors.affiliation: AstraZeneca, Innovative Medicines, Drug Safety Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Wilkinson
authors.affiliation: AstraZeneca, Innovative Medicines, Drug Safety Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Robinson
authors.affiliation: AstraZeneca, Innovative Medicines, Drug Safety Metabolism, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
mesh_terms: D000818:Animals; D001800:Blood Specimen Collection / Q000379:methods*; D001831:Body Temperature; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D006403:Hematologic Tests; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013154:Spleen / Q000033:anatomy & histology; D018675:Toxicity Tests / Q000379:methods*
keywords: Blood; Clinical chemistry parameters; Haematology; Microsampling; Rodent; Toxicokinetic