"Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

- Time schedule: Twice daily (a.m. and p.m.)

- Cage side observations checked in table 1 and Appendix B were included.

BODY WEIGHT: Yes

- Time schedule for examinations: At randomization, on the first day of treatment and weekly thereafter.

FOOD CONSUMPTION:

- Food consumption for each animal determined: Weekly

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes

- Time schedule for collection of blood: During Week 5

- Anaesthetic used for blood collection: Yes, ketamine

- Animals fasted: Yes

- How many animals: All animals

- Parameters checked in tables 5-8 were examined.

CLINICAL CHEMISTRY: Yes

- Time schedule for collection of blood: During Week 5

- Animals fasted: Yes

- How many animals: All animals

- Parameters checked in tables 5-8 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Statistics:

Levene's test was done to test for variance homogeneity. ANOVA analysis was done on the homogenous or transformed data. If ANOVA was significatn, Dunnett's t-test was used for pairwise comparisons between treated and control groups. One-way ANOVA was used to analyze body weights, cumulative body weight gains, food consumption, clinical chemistry and hematology values( except red blood cell morphology), organ weights, organ-to-body weight percentages, and organ-to-brain weight ratios...

Rats were observed twice daily (a.m. and p.m.) for mortality and moribundity, and predose and 1.5 hours postdose for indications of toxic effects. Blood samples were collected from all animals before terminal sacrice for hematology and clinical chemistry analyses. After 4 weeks of treatment, the animals were fasted overnight, anesthetized with sodium pentobarbital, weighed, exsanguinated, and necropsied. At necropsy, all animals were examined macroscopically and selected tissues were weighed and preserved in 10% phosphate buffered formalin. Tissues from all animals in control and high-dose groups were sectioned, stained, and examined microscopically. No signicant treatment-related effects were observed."

Male and Female Crl:CDBR VAF/Plus Rats