“CAGE SIDE OBSERVATIONS: Yes - Time schedule: Once daily DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Once daily

BODY WEIGHT: Yes - Time schedule for examinations: All animals were weighed as follows: Before dosing day -2 (at grouping); During dosing period: day 1,3,5,8,10, 12,15,17,19,22,24,26, and 28; During recovery period: day 1,3,5,8,10,12, and 14.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes. Food consumption was measure as follows: Before dosing: Once; During dosing and recovery periods: Twice weekly

FOOD EFFICIENCY: - Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes - Time schedule for collection of blood: at termination of dosing and recovery periods - Anaesthetic used for blood collection: Yes (ether) - Animals fasted: Yes (16-20 hours) - How many animals: All animals - Parameters checked in table [No.2] were examined.

CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: at termination of dosing and recovery periods - Animals fasted: Yes (16-20 hours) - How many animals: All animals - Parameters checked in table [No.3] were examined.

URINALYSIS: Yes - Time schedule for collection of urine: During dosing period: Once (Day 28); During recovery period: Once (Day 14) - Metabolism cages used for collection of urine: Yes - Animals fasted: Not specified - Parameters examined: volume, colour, additional items of pH, protein, ketone bodies, bilirubin, occult blood, glucose, and urobilinogen using a test paper (N-Multistix®, MilesSankyo)

GROSS PATHOLOGY: Yes Animals were subjected to a detailed gross necropsy abnormalities recorded. Following organs were recorded in wet weight: Brain, Liver, Spleen, Kidneys, Adrenal glands, Testes, Ovaries HISTOPATHOLOGY: Yes 1) The organs and tissues mentioned in Table No. 4. were preserved in 10% formalin:

2) Light microscopic examinations were performed for the following organs and tissues after embedding in paraffin, sectioning and staining with hematoxylin and eosin.

a) Terminal necropsy of dosing period: Vehicle Control and 1000 mg/Kg groups: Liver, Spleen, Kidneys, Heart, Stomach, Intestine (Duodenum, Jejunum, Ileum, Cecum, Colon, Rectum), Adrenal glands.

b) Gross lesions: Terminal necropsy of dosing period: 200 mg/Kg group (Male No. 24): Glandular stomach; 40 mg/Kg group (Male No. 16): Glandular stomach; 40 mg/Kg group (Female No. 49): Hindlimb

c) Terminal necropsy of recovery period: Vehicle control group (Male Nos. 10 and 11): Glandular stomach; 1000 mg/Kg group (Female No. 71): Glandular stomach; 1000 mg/Kg group (Female No. 68): Skin

Statistics: Data regarding body weights, food consumption, hematological examinations, blood chemical examinations, urine volume and organ weights were analyzed using the Bartlett's test for homogeneity of variance. If the variances were homogenous at a significance level of 5%, one way analysis of variance was performed. If there was a significant difference in this analysis, the difference between the vehicle control group and each of the treatment groups was analyzed by the Dunnett's test (equal number of data) or Scheffe's test (unequal number of data). If the variances were not homogenous the Kruskal Wallis test was used. If there was a significant difference in this analysis, the difference between the vehicle control group and each of the treatment groups was analyzed by the non parametric Dunnett's test (equal number of data) or non parametric Scheffe's test (unequal number of data).”

Stomach Histopathology

Endpoint Details

Dataset

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