Study Director, Ruschelle Love, received acceptance from the Society of Toxicology (SOT) for her abstract submission entitled “Hematopoeitic Characteristics Of The Macaque Following A Single Dose Of Irradiation”
Hematopoeitic Characteristics Of The Macaque Following A Single Dose Of Irradiation
In continuing efforts to develop well defined animal models for the acute radiation syndrome under the FDA Animal Rule (21CR314, subpart 1), whole body irradiation (TBI) was applied to six cynomolgus macaques at a total dose of 7.55 Gy using a LINAC source. The irradiation was performed in two half –dose fractions each of 3.775 Gy (antero-posterior and postero-anterior).
Various parameters were monitored for 59 days including hematology (24 time points), body weights, body temperature, food consumption, cageside and detailed clinical observations. A well defined veterinary medical treatment regimen and supportive care measures were provided for the irradiated animals. Necropsy was performed on day 59 and organs and tissues were evaluated macro and microscopically.
Results: 50% of the animals were euthanized by day 37. As expected following accurate TBI, decreases in neutrophil and platelet parameters were seen following irradiation on day 1. Study endpoints, in addition to survival, included the cell nadirs, the day of and duration of neutropenia (ANC <500µL, ANC <100µL) and thrombocytopenia (PLT <20,000µL), and time to recovery to an ANC >1,000µL and PLT >20,000µL. Lethal doses of TBI administered reduced the circulating ANC to <500µL by day 8 for all irradiated animals and to <100µL between day 10 and day 12. The average nadir at 7.55 Gy was 18µL. The ANC of survivors recovered to ≥100 µL by day 22 and one non-survivor recovered to this level on day 28. Only surviving animals attained recovery to ANC ≥500 µL (between day 22 and day 25). The first day the PLT count decreased to <10,000µL ranged from day 12 to day 14. The PLT count continued to decrease and the duration of thrombocytopenia (PLT <20,000 µL) ranged from day 12 to day 25 for surviving (and the one non-survivor) animals, with the exception of one survivor (SSAN 10) that showed decreased counts sporadically until scheduled necropsy on day 59. The animals required a range of 10 to 20 days to recover to PLT counts ≥20,000µL, with the exception of one animal discussed above (SSAN 10) who showed continued sporadic decreases. The results of this study support an LD50/59 of 7.55 Gy..
R. Love1 N. Makori1 S. Glaza1 T. Beck1 K. Fukuzaki1
1SNBL USA, Ltd., Everett, WA, USA; 2Shin Nippon Biomedical Laboratories, Ltd., /Kagoshima, Japan