Differences in hematologic variables in rats of the same strain but different origin

Abstract

Wistar rats are frequently used in toxicologic studies; however, the impact of animal source on hematologic reference intervals (RI) is not known. The purpose of this study was to compare hematologic data of Wistar rats obtained from 2 breeders and to calculate preliminary RI for the Sysmex XT-2000iV hematology analyzer. Blood collected in EDTA from 75 10-13-week-old rats (male, n = 38; female, n = 37) from breeder 1 and 60 rats (male, n = 30; female, n = 30) from breeder 2 was analyzed using a Sysmex XT-2000iV hematology analyzer. Results were analyzed for differences using a t-test or Mann-Whitney U-test. Sex-specific 95% RI were calculated for rats from both breeders. Significant breeder-specific differences were found for WBC, RBC, platelet, lymphocyte, monocyte, eosinophil, and reticulocyte counts and MCV, MCH, MPV, and plateletcrit for both sexes, and for HCT and hemoglobin concentration for female rats. The greatest differences (P < .0001) between rats from breeders 1 and 2, respectively, were found for WBC (female: 2.2-5.9 × 10(9) /L vs 4.2-9.4 × 10(9) /L 38; male: 3.4-9.5 vs 6.4-14.4 × 10(9) /L), lymphocyte (female: 1.7-4.8 × 10(9) /L vs 3.4-8.2 × 10(9) /L; male: 2.6-7.8 vs 5.2-12.4 × 10(9) /L), and platelet (female: 591-836 × 10(9) /L vs 804-1282 × 10(9) /L; male: 573-998 × 10(9) /L vs 861-1247 × 10(9) /L) counts. Differences in hematologic RI between Wistar rats obtained from different breeders underscore the need to evaluate untreated control animals for comparison, rather than using historical RI, to detect compound-related effects in preclinical safety studies. Valid RI for control animals are needed and should be verified when using a new supplier to avoid misinterpretation of data. Low reference limits for some variables, such as WBC counts, in rats from one source may preclude their use in studies in which detection of leukopenia is required.