TABLE 3.
Summary of functional observation battery test measurements in females in the repeat-dose 90-day toxicity study. The numbers represent the number of animals showing the respective observations. *Statistically significant (p < 0.05) with respect to the control group (vehicle).
| Group no. | Paraxanthine | Caffeine | |||||
|---|---|---|---|---|---|---|---|
| Dose (mg/kg b.w.) | 0 | 100 | 150 | 185 | 150 | 185 | |
| Number of animals | 10 | 10 | 10 | 10 | 10 | 10 | |
| Open field measurement | |||||||
| A. Gait | |||||||
| 1 | Normal | 10 | 10 | 10 | 9 | 10 | 9 |
| 2 | Ataxia, uncoordinated movement, excessive sway, rock, or lurch (stop and sudden movement) | 0 | 0 | 0 | 1 | 0 | 0 |
| 3 | Body drags or is flattened (animal’s ventral surface makes contact with the cart surface) | 0 | 0 | 0 | 0 | 0 | 1 |
| 4 | Limbs splayed or dragging; unable to support weight (specify hind or forelimbs) | 0 | 0 | 0 | 0 | 0 | 0 |
| B. Mobility | |||||||
| 1 | Normal (animal moves easily around open field) | 10 | 6 | 10 | 7 | 10 | 9 |
| 2 | Increased movement (animal moves mostly continuously, rarely stopping to sniff or groom) | 0 | 4 | 0 | 1 | 0 | 0 |
| 3 | Decreased movement (reduced movement around field; movements may be sluggish) | 0 | 0 | 0 | 2 | 0 | 1 |
| 4 | None (animal does not move around field even after gently prodding) | 0 | 0 | 0 | 0 | 0 | 0 |
| C. Arousal | |||||||
| 1 | Normal and alert with exploratory movements | 10 | 10 | 10 | 3 | 5 | 3 |
| 2 | Low; slight stupor, some head or body movements | 0 | 0 | 0 | 0 | 1 | 1 |
| 3 | Very low; stupor, little or no responsiveness to the environment | 0 | 0 | 0 | 2 | 0 | 0 |
| 4 | High; slight excitement, tense, sudden darting (sudden rapid movement) or freezing | 0 | 0 | 0 | 5 | 4 | 6 |
| 5 | Very high; hyper alert, sudden boost of running or movement | 0 | 0 | 0 | 0 | 0 | 0 |
| D. Stereotype | |||||||
| 1 | None | 10 | 10 | 10 | 10 | 6 | 10 |
| 2 | Excessive grooming | 0 | 0 | 0 | 0 | 3 | 0 |
| 3 | Repetitive circling | 0 | 0 | 0 | 0 | 0 | 0 |
| 4 | Any other (Dragging lower jaw against the floor) | 0 | 0 | 0 | 0 | 1 | 0 |
| E. Piloerection | |||||||
| 1 | Absent | 10 | 10 | 10 | 10 | 10 | 10 |
| 2 | Present | 0 | 0 | 0 | 0 | 0 | 0 |
| F. Clonic and tonic movement | |||||||
| 1 | Absent | 10 | 10 | 10 | 10 | 10 | 10 |
| 2 | Present | 0 | 0 | 0 | 0 | 0 | 0 |
| G. Number of Urinations | |||||||
| Mean | 2.70 | 1.20 | 1.50 | 1.20 | 0.70* | 0.90 | |
| STDEV (±) | 2.11 | 1.23 | 1.90 | 1.93 | 1.06 | 0.91 | |
| H. Number of Defecations | |||||||
| Mean | 0.00 | 0.10 | 0.20 | 0.20 | 0.20 | 0.30 | |
| STDEV (±) | 0.00 | 0.32 | 0.42 | 0.42 | 0.42 | 0.67 | |
| I. Number of rearing | |||||||
| Mean | 11.40 | 14.00 | 13.40 | 7.80 | 9.70 | 9.20 | |
| STDEV (±) | 4.60 | 4.14 | 3.81 | 5.55 | 3.40 | 2.90 | |
| J. Foot splay (cms) | |||||||
| Mean | 5.96 | 6.76 | 6.55 | 5.30 | 7.03 | 5.74 | |
| SD (±) | 1.96 | 1.18 | 1.37 | 1.57 | 1.53 | 1.06 | |