"CLINICAL OBSERVATIONS: The summary of clinical observations is in Table 1. The individual clinical observations are in Appendix 4. Clinical observations consisted of localized alopecia (back, limbs, neck, and underside), urine-stained abdominal fur, scabbed area on back and neck, and soft or liquid feces. These findings are considered incidental and unrelated to test material administration. Additional cageside observations were all normal.

NEUROLOGICAL.FUNCTION OBSERVATIONS: The results of the neurological function examinations performed during Week 4 are located in Appendix 6. The summary and individual motor activity data are presented in Table 2 and Appendix 5, respectively. Assessment of neurological effects on animals treated with T-7485 included peripheral neuropathy, motor activity, and audio/visual evaluations. There were no test material-related effects on motor activity or audio/visual. Interpretation of peripheral neurological findings suggests no test material-related neuropathology, but within this evaluation the significant findings for the tail flick examination may suggest that T-7485 induces a male-specific doseindependent hyperreactivity.

BODY WEIGHTS AND BODY WEIGHT CHANGES: The summaries of body weights and body weight changes are in Tables 3 and 4, respectively. The individual body weights are in Appendix 7. There were no treatment-related effects on body weights for either Main Study or Recovery animals. On Study Day 36, the mean body weight in males that received 900 mg/kg/day T-7485 was decreased by 7% when compared to the corresponding controls. This finding was considered incidental. Throughout the study, body weight changes in treatment groups were calculated and compared to the corresponding control groups with no significant findings recorded for either Main Study or Recovery animals.

FEED CONSUMPTION: The summary of absolute feed consumption is in Table 5. The individual data are in Appendix 8. Throughout the study, absolute feed consumption per treatment group was calculated and compared to the corresponding control groups with no significant findings recorded for either Main Study or Recovery animals.

HEMATOLOGY: The summary of hematology data is in Table 6. The individual data are in Appendix 9. The reported significant hematological findings are considered incidental and not associated with test material administration.

CLINICAL CHEMISTRY: The summary of clinical chemistry data is in Table 7. The individual data are in Appendix 10.Main Study findings in males that received 2:300 mg/kg/day T-7485 indicate significant decreases in serum phosphorus (approximately 16% of the control values) and potassium (approximately 20% of the control values). In contrast, an increase in chloride levels in males that received 900 mg/kg/day T-7485 (4% above the control values) was recorded. In the absence of similar findings in Recovery animals, the changes in phosphorus, potassium, and ch!-oride levels appear to be associated with test material administration but do not appear to be toxicologically or biologically significant, as indicated by historical data (Primedica, Appendix 11 ). Other incidental findings do not appear to be related to administration of the test material.

NECROPSY: The individual necropsy observations are in Appendix 2. Only one gross lesion was recorded at necropsy and was not considered to be test materialrelated.

ORGAN WEIGHTS: The summary of organ weights is in Table 8. The individual data are in Appendix 12. Absolute and relative male liver (between 25% to 30%) and female kidney (9% to 11 %) weights were significantly increased in animals that received 900 mg/kg/day T-7485 when compared to the corresponding controls. These significant changes were not recorded during the recovery period, and since there does not appear to be an effect of body weight on organ development, these data suggest the changes are test material-related. However, the biological and toxicological significance is unclear due to the lack of any supportive gross or histopathological findings. The remaining significant findings are considered incidental and unrelated to test material administration.

HISTOPATHOLOGY: The histopathology report is located in Appendix 3. The microscopic lesions observed in the test animals are considered to be incidental and in no way related to receiving the test material."

Hemorrhage, Terminal

Endpoint Details

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