Selection of CRO for Preclinical Toxicity and Formulation Development studies

STUDY-1

Study-I Product- II- Efficacy of Test compounds in Monoiodoacetate Model of Osteoarthritis Pain in Rat Animal Welfare: Studies to be done as per IAEC (CPCSEA) approved Protocols (1)- Test System Species: Rat Strain: Wistar Sex, Age: Male/Female, 6-8 weeks Procedure: Animals is to be anaesthetized and given single intra-articular injection of 1 mg of monosodium iodoacetate (MIA) through the infrapatellar ligament of the right knee. Sterile saline: used for injections in normal control animals Treatment start: 5/7 days post MIA injection. Treatment end: Animals to be terminated 28/56 day post MIA injection. Efficacy Readout: • Body weights • Mechanical hyperalgesia • Histopathology • Clinical Observations: General clinical signs Analysis: One way ANOVA (95 % confidence level) Group Treatment No. of animals / group 1 Normal control 10 2 Control 10 3 Reference Control 10 4 Test Dose -1 10 5 Test Dose-2 10 6 Test Dose -3 10

STUDY-2

Product- II, Acute Toxicology Studies (Two Species: Mice and Rat) Acute single dose oral toxicity of Phytopharmaceutical lead (Product- II) in mice and rat by oral route as per Appendix III of Schedule Y (GLP study). Report of study should include all results, raw data, interpretations, observations, conclusions.

STUDY-3

Product- II, 10 days Dose ranging finding (DRF) studies 10-days dose-range finding (DRF) study (non-GLP study) of Phytopharmaceutical lead (Product- II ) in rat to identify a dose-range for 28-days repeated dose toxicity study

STUDY-4

Product- II, Sub Acute Toxicology Studies (28 days) in rat 28-days repeated dose oral toxicity study of Phytopharmaceutical lead (Product- II) in rat as per Appendix III of Schedule Y (GLP study) Report of study should include all results, raw data, interpretations, observations, conclusions.

Dabur Research Foundation