Table 13.
Thirteen-weeks repeated dose toxicity and four-weeks recovery study: Urinalysis of male dogs (main study) and urinalysis of female dogs (Main study)
| Summary of urinalysis (sex: male) | ||||
|---|---|---|---|---|
| Test item | Main group (mg/kg/day) | |||
| G1 (0) | G2 (250) | G3 (500) | G4 (1000) | |
| Glucose | ||||
| Negative | 5/5 | 3/3 | 3/3 | 5/5 |
| Bilirubin | ||||
| Negative | 1/5 | 1/3 | 1/3 | 0/5 |
| 1+ | 3/5 | 1/3 | 2/3 | 3/5 |
| 2+ | 1/5 | 1/3 | 0/3 | 2/5 |
| Ketone body* | ||||
| Negative | 4/5 | 2/3 | 0/3 | 1/5 |
| Trace | 1/5 | 2/3 | 1/3 | 4/5 |
| 1+ | 0/5 | 1/3 | 2/3 | 0/5 |
| Specific gravity | ||||
| 1.010 | 2/5 | 2/3 | 0/3 | 1/5 |
| 1.015 | 0/5 | 0/3 | 0/3 | 2/5 |
| 1.020 | 1/5 | 0/3 | 0/3 | 0/5 |
| 1.025 | 0/5 | 0/3 | 1/3 | 2/5 |
| 1.030 | 2/5 | 1/3 | 2/3 | 0/5 |
| Occult blood | ||||
| Negative | 3/5 | 2/3 | 3/3 | 2/5 |
| Trace | 0/5 | 0/3 | 0/3 | 3/5 |
| 1+ | 1/5 | 0/3 | 0/3 | 0/5 |
| 2+ | 1/5 | 1/3 | 0/3 | 0/5 |
| pH | ||||
| 5.5 | 2/5 | 1/3 | 2/3 | 1/5 |
| 6.0 | 2/5 | 1/3 | 2/3 | 0/5 |
| 6.5 | 0/5 | 0/3 | 1/3 | 1/5 |
| 7.0 | 1/5 | 0/3 | 0/3 | 2/5 |
| 8.0 | 0/5 | 1/3 | 0/3 | 1/5 |
| 8.5 | 2/5 | 1/3 | 0/3 | 0/5 |
| Protein* | ||||
| Negative | 4/5 | 1/3 | 3/3 | 1/5 |
| Trace | 0/5 | 0/3 | 0/3 | 4/5 |
| 1+ | 1/5 | 2/3 | 0/3 | 0/5 |
| Urobilinogen | ||||
| 0.2 | 0/5 | 0/3 | 0/3 | 0/5 |
| Nitrite | ||||
| Negative | 3/5 | 2/3 | 2/3 | 3/5 |
| Positive | 2/5 | 1/3 | 1/3 | 2/5 |
| Leukocyte | ||||
| Negative | 2/5 | 1/3 | 2/3 | 0/5 |
| Trace | 0/5 | 0/3 | 1/3 | 2/5 |
| 1+ | 2/5 | 1/3 | 0/3 | 2/5 |
| 2+ | 0/5 | 0/3 | 0/3 | 1/5 |
| 3+ | 1/5 | 1/3 | 0/3 | 0/5 |
| Color | ||||
| Straw | 5/5 | 3/3 | 3/3 | 5/5 |
| Summary of urinalysis (sex: female) | ||||
|---|---|---|---|---|
| Test item | Main group (mg/kg/day) | |||
| G1(0) | G2 (250) | G3 (500) | G4 (1000) | |
| Glucose | ||||
| Negative | 5/5 | 3/3 | 3/3 | 5/5 |
| Bilirubin | ||||
| Negative | 5/5 | 2/3 | 3/3 | 3/5 |
| 1+ | 0/5 | 1/3 | 0/3 | 2/5 |
| Ketone body | ||||
| Negative | 3/5 | 0/3 | 1/3 | 2/5 |
| Trace | 0/5 | 2/3 | 1/3 | 1/5 |
| 1+ | 2/5 | 1/3 | 1/3 | 2/5 |
| Specific gravity | ||||
| ≤ 1.005 | 1/5 | 0/3 | 0/3 | 2/5 |
| 1.010 | 3/5 | 1/3 | 1/3 | 0/5 |
| 1.015 | 0/5 | 0/3 | 1/3 | 3/5 |
| 1.020 | 1/5 | 1/3 | 0/3 | 0/5 |
| 1.030 | 0/5 | 1/3 | 1/3 | 0/5 |
| Occult blood | ||||
| Negative | 2/5 | 1/3 | 3/3 | 0/5 |
| Trace | 1/5 | 1/3 | 0/3 | 4/5 |
| 1+ | 0/5 | 0/3 | 0/3 | 1/5 |
| 2+ | 1/5 | 0/3 | 0/3 | 0/5 |
| 3+ | 1/5 | 1/3 | 0/3 | 0/5 |
| pH | ||||
| 6.0 | 0/5 | 1/3 | 0/3 | 0/5 |
| 6.5 | 0/5 | 0/3 | 1/3 | 0/5 |
| 7.0 | 0/5 | 1/3 | 1/3 | 2/5 |
| 7.5 | 2/5 | 1/3 | 0/3 | 2/5 |
| 8.0 | 1/5 | 0/3 | 0/3 | 0/5 |
| 8.5 | 2/5 | 0/3 | 1/3 | 1/5 |
| Protein | ||||
| Negative | 4/5 | 3/3 | 2/3 | 5/5 |
| Trace | 1/5 | 0/3 | 1/3 | 0/5 |
| Urobilinogen | ||||
| 0.2 | 5/5 | 3/3 | 3/3 | 5/5 |
| Nitrite | ||||
| Negative | 2/5 | 2/3 | 1/3 | 3/5 |
| Positive | 3/5 | 1/3 | 2/3 | 2/5 |
| Leukocyte | ||||
| Negative | 5/5 | 2/3 | 3/3 | 5/5 |
| 2+ | 0/5 | 1/3 | 0/3 | 0/5 |
| Color | ||||
| Straw | 5/5 | 3/3 | 3/3 | 5/5 |
Number of animals with the sign/number of animals examined
Significant difference compared with the control group value, *p < 0.05