Cumene-derived radioactivity in all surveyed tissues 24 h after single or repeat dosing (consecutive daily dosing) of 14 mg/kg to male rats and 150 mg/kg to female mice
Each values represents the mean ± S.D. of four animals per treatment group.
| Tissue | Male Rat | Female Mouse | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 Dose | 3 Doses | 7 Doses | 1 Dose | 3 Doses | 7 Doses | |||||||
| Conc. | T/B | Conc. | T/B | Conc. | T/B | Conc. | T/B | Conc. | T/B | Conc. | T/B | |
| nmol-Eq/g | nmol-Eq/g | nmol-Eq/g | nmol-Eq/g | nmol-Eq/g | nmol-Eq/g | |||||||
| Adipose | 12 ± 7 | 3.1 ± 1.7 | 14 ± 9 | 2.6 ± 2.0 | 9.0 ± 7.4 | 1.3 ± 0.6 | 1.4 ± 0.5 | 0.89 ± 0.56 | 2.9 ± 1.1 | 0.52 ± 0.23 | 3.6 ± 2.1 | 0.41 ± 0.32 |
| Urinary Bladder | 72 ± 38 | 19 ± 12 | 971 ± 1126 | 152 ± 154 | 106 ± 81 | 14 ± 10 | 1.8 ± 0.3 | 1.1 ± 0.3 | 11 ± 10 | 2.1 ± 2.1 | 26 ± 35 | 3.3 ± 5.0 |
| Blood | 3.8 ± 0.3 | Unity | 5.8 ± 1.1* | Unity | 6.3 ± 2.7 | Unity | 1.8 ± 0.5 | Unity | 5.7 ± 0.7* | Unity | 9.5 ± 2.2*# | Unity |
| Brain | 1.4 ± 0.2 | 0.37 ± 0.04 | 3.2 ± 1.2 | 0.56 ± 0.25 | 2.1 ± 1.0 | 0.34 ± 0.03 | 1.1 ± 0.4 | 0.65 ± 0.22 | 2.3 ± 0.3* | 0.41 ± 0.05 | 3.0 ± 0.6* | 0.33 ± 0.11 |
| Heart | 2.4 ± 0.3 | 0.63 ± 0.06 | 4.0 ± 1.2 | 0.69 ± 0.10 | 4.0 ± 1.6 | 0.63 ± 0.03 | 1.4 ± 0.1 | 0.85 ± 0.23 | 3.7 ± 0.7* | 0.65 ± 0.09 | 5.3 ± 0.7*# | 0.58 ± 0. |
| Kidney | 33 ± 3 | 8.6 ± 1.7 | 60 ± 27 | 10 ± 4 | 57 ± 19 | 9.5 ± 1.8 | 4.0 ± 0.9 | 2.3 ± 0.4 | 16 ± 2* | 2.8 ± 0.2 | 20 ± 2*# | 2.2 ± 0.6 |
| Liver | 22 ± 3 | 5.9 ± 1.4 | 31 ± 9 | 5.4 ± 1.1 | 32 ± 21 | 4.8 ± 1.2 | 7.6 ± 1.7 | 4.7 ± 2.1 | 26 ± 4* | 4.6 ± 0.9 | 28 ± 5* | 3.0 ± 0.2 |
| Lung | 6.1 ± 2.6 | 1.6 ± 0.6 | 6.6 ± 1.8 | 1.1 ± 0.1 | 7.4 ± 2.3 | 1.3 ± 0.4 | 7.9 ± 1.2 | 4.6 ± 0.8 | 19 ± 1* | 3.4 ± 0.4 | 31 ± 7*# | 3.4 ± 1.1 |
| Muscle | 1.0 ± 0.5 | 0.27 ± 0.13 | 2.8 ± 0.1* | 0.49 ± 0.07 | 1.9 ± 1.4 | 0.29 ± 0.16 | 0.87 ± 0.12 | 0.51 ± 0.13 | 2.4 ± 0.4* | 0.43 ± 0.07 | 2.8 ± 0.9* | 0.30 ± 0.05 |
| Skin | 2.5 ± 0.5 | 0.66 ± 0.17 | 5.8 ± 1.8* | 1.0 ± 0.3 | 7.3 ± 2.9* | 1.2 ± 0.5 | 4.7 ± 2.9 | 2.5 ± 1.1 | 7.7 ± 2.0 | 1.4 ± 0.4 | 23 ± 13 | 2.7 ± 2.2 |
| Spleen | 2.4 ± 0.8 | 0.62 ± 0.17 | 5.4 ± 1.4* | 0.94 ± 0.23 | 5.7 ± 3.2 | 0.91 ± 0.35 | 1.6 ± 0.3 | 0.94 ± 0.12 | 4.1 ± 0.4* | 0.72 ± 0.12 | 6.2 ± 1.6* | 0.70 ± 0.32 |
| Thyroid | 0.0 ± 6.5 | 0.1 ± 1.8 | 3.8 ± 1.9 | 0.63 ± 0.22 | 2.9 ± 2.9 | 0.49 ± 0.61 | 8.9 ± 7.0 | 5.3 ± 3.5 | N.D | N.A. | N.D | N.A. |
| Testes | 1.3 ± 0.4 | 0.33 ± 0.12 | 9.1 ± 7.0 | 1.6 ± 1.3 | 1.8 ± 1.1 | 0.28 ± 0.05 | 1.3 ± 0.0 | 0.78 ± 0.21 | 4.4 ± 2.7 | 0.90 ± 0.54 | 15 ± 22 | 2.5 ± 3.2 |
T/B, tissue/blood ratio; N.D., not detected: the average concentration was <0 after background correction; N.A., not applicable.
↵* Statistically higher (p ≤ 0.05) in the same tissues from three or seven dose studies versus the single-dose study.
↵# Statistically higher (p ≤ 0.05) in the same tissues from the seven-dose study versus the three-dose study.