Acl 8000

Clinical pathology analysis was performed on Days 15, 35 and 57 in rats, and at pretreatment and on Days 15, 29 and 50 in dogs. In rats, blood samples were collected from the retro-orbital venous plexus for hematology and clinical chemistry parameters, and via posterior vena cava for coagulation parameters. In dogs, blood samples were collected either from cephalic or saphenous veins. Animals were fasted overnight prior to sample collection. Various hematological (Advia 120, Siemens, Germany), clinical chemistry (Cobas c 501, Roche, Switzerland) and coagulation parameters (ACL 8000, Beckman Coulter, USA) were analyzed in both rats and dogs (see Supplementary Tables S1–S3 for list of parameters).

Blood samples for clinical pathology assessment (hematology, clinical chemistry, and coagulation) were collected pre-test (Day −3) and, for one or more dose groups on Days 22, 55, 85, 106, 134, 160, 176, and 189. When possible, clinical pathology specimens were collected prior to unscheduled euthanasia for moribund animals. All clinical pathology blood samples were collected from a jugular vein. Standard hematological (Advia 120, Siemens, Germany), clinical chemistry (Cobas c 501, Roche, Switzerland), and coagulation parameters (ACL 8000, Beckman Coulter, USA) were analyzed. Urine analysis (Roche Cobas u 411 urine analyzer) and urine chemistry (Roche Cobas c 501 chemistry analyzer) were performed on urine specimens collected overnight pre-test and during Weeks 4, 13, 16 (Group 3 males only), 20 (Group 3 males only), 23, and 27. For the list of analytes evaluated see Supplementary Tables S2–S6.