T-7145 was administered orally to male and female Sprague-Dawley rats (5 animals/sex/dose) for 28 days at doses of 0, 40, 200, and 1000 mg/kg. The animals were either sacrificed on day 29 to study toxicity of the test compound , or allowed a 14 days recovery post exposure and sacrificed on day 43 to examine reversibility.

"Details on test material: analytical purity (99.89%), impurities identity and concentration (0.11% unidentified), stable under test condition." "storage condition of test material: room temperature in air-tight container."

Cage side observation: daily for 4 weeks

Hematology: 5 animals/sex/ dose were used for hematology on Day 29 and 43 at the scheduled sacrificed

Detailed clinical observation: Conducted twice/day during treatment. Once per day on every other day in the morning.

Body weight: All rats were weighed once a week and the day before necropsy

Food Consumption and compound intake: once/week

Neurobehavioral Examination: Detailed clinical observation were made in all animals once before the first administration (the day before first administration) and once a week (Days 5, 12, 19, and 28) in the afternoon during the treatment period.

Outcomes: Clinical chemistry, urinalysis, neurobehavioral examination, gross pathology, histopathology, food consumption, body weight and weight gain, food efficiency, water consumption and compound in take, organ weights (spleen, adrenals, ovaries, epididymides)

Statistics:

"The numerical data were analyzed by multiple comparison tests. They were first analyzed by Bartlett's test. If the group variance was determined to be homogenous, all groups were compared by a one-way analysis of variance. If the Bartlett's test indicated heterogenous variance, the Kruskal-Wallis test was employed , and a Dunnett's test or Dunnett type multiple comparison was used when there was a significant difference between the groups. The categorical were analyzed by R x C Chi-square test, and when there was significance, Armitage's Chi-square test was used to compare the difference between the control group and each treatment group. Statistical analysis was performed on items listed below. The analysis was not performed on clinical signs, functional observation (detailed clinical observations, sensory reactivity to stimuli), necropsy, or histological findings.

Multiple comparison test: Body weight, functional observations (forelimb grip strength, hindlimb grip strength, and motor activity), food consumption

Chi-square test: urinalysis (pH, protein, glucose, ketone bodies, bilirubin, occult blood, and urobilinogen)"

Liver Histopathology

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