Oxy-Powder®
28-Day Safety Study Sub-Chronic Toxicity Report

PROJECT NO.12204
SUBCHRONIC ORAL TOXICITY STUDY (28 DAY) OF OXY-POWDER®
IN THE SPRAGUE DAWLEY RAT

The Sub-Chronic oral toxicity study was designed and conducted to determine the toxicity profile of Oxy-Powder® when administered daily for 28 days in Sprague Dawley rats. In the acute toxicity test the compound was found to be non toxic at the dose level of 5000 mg/kg body weight. The dose has been selected on this basis and the justification provided on page 14 of this report.

Oxy-Powder® suspended in distilled water was administered to animals at the dose levels 250 mg/kg, 500 mg/kg and 1000 mg/kg body weight. Two additional dose levels were added to the study as 0 mg/kg (Rev.) and 1000 mg/kg (Rev.), in order to study the reversibility or delayed occurrence of symptoms, if any. The control animals were administered with vehicle only.

Salient features of the study were as follows:

1. All the male and female animals from control and all the treated dose groups up to 1000 mg/kg survived throughout the dosing period of 28 days and the recovery period of 14 days.
2. No signs of intoxication were observed in male and female animals from different dose groups during the dosing period of 28 days and during the recovery period of 14 days.
3. Male and female animals from all the treated dose groups exhibited comparable body weight gain with that of controls throughout the dosing period of 28 days and the recovery period of 14 days.
4. Food consumption of control and treated animals was found to be comparable throughout the dosing period of 28 days and the recovery period of 14 days.
5. Ophthalmoscopic examination, conducted prior to and at the end of dosing period on animals from control and all the treated dose groups did not reveal any abnormality.
6. Hematological analysis conducted at the end of the dosing period on day 29 and at the end of recovery period on day 43, revealed no abnormalities attributable to the treatment.
7. Biochemical analysis conducted at the end of the dosing period on day 29 and at the end of recovery period on day 43, revealed no abnormalities attributable to the treatment.
8. Functional battery observation tests conducted at termination revealed no abnormalities.
9. Urine analysis, conducted at the end of the dosing period in week 4 and at the end of recovery period in week 6, revealed no abnormality attributable to the treatment.
10. Organ weight data of male and female sacrificed at the end of the dosing period and at the end of the recovery period was found to be comparable with that of respective controls.
11. Gross pathological examination did not reveal any abnormality.
12. Histopathological examination did not reveal any abnormality.

Based on these findings the no observed effect level (NOEL) of Oxy-Powder® supplied by Mayfair Clinical Education and Research Centre, Mumbai, in Sprague Dawley rat via oral route, over a period of 28 days was found to be 1000 mg/kg body weight for male and female animals.