Toxicity Studies in Rodents

General 14-Day Protocol (No Recovery Groups)

• Groups of 5 males and 5 females are treated with the test substance by gavage at 3 dose levels for 14 days; a vehicle control group is included (40 animals total)
• Study measurements include daily clinical observations, weekly body weights, and feed consumption
• Hematology and serum clinical chemistry evaluations at termination
• Necropsies are performed on any animals that die or upon termination; weights are recorded for major organs
• Full histopathological examinations are conducted on the control and high-dose groups and on any unscheduled deaths

Comprehensive 28-Day Protocol (Recovery Groups Included)

• Groups of 5 males and 5 females are treated with the test substance by gavage at 3 dose levels for 14 days; a vehicle control group is included (40 animals total)
• Study measurements include daily clinical observations, weekly body weights, and feed consumption
• Hematology and serum clinical chemistry evaluations at termination
• Necropsies are performed on any animals that die or upon termination; weights are recorded for major organs
• Full histopathological examinations are conducted on the control and high-dose groups and on any unscheduled deaths (at 14 days)
• Additional recovery group with 5 males and 5 females per dose level (80 rats total) Recovery group evaluated on day 28

General 28-Day Oral Toxicity Study (No Recovery Groups)

• Groups of 10 males and 10 females are treated with the test substance by gavage at 3 dose levels for 28 days; a vehicle control group is included (80 rats total)
• Study measurements include daily clinical observations, weekly body weights and feed consumption, and ophthalmological examination pretest and at study termination
• Hematology, serum clinical chemistry and urinalysis evaluations at termination
• Necropsies are performed on any animals that die or upon termination; weights are recorded for major organs
• Full histopathological examinations are conducted on the control and high-dose groups and on any unscheduled deaths
• Target organs are examined in the intermediate groups

Comprehensive 28-Day Toxicity Study (Recovery Groups Included)

• Groups of 10 males and 10 females are treated with the test substance by gavage at 3 dose levels for 28 days; a vehicle control group is included (80 rats total)
• Study measurements include daily clinical observations, weekly body weights and feed consumption, and ophthalmological examination pretest and at study termination
• Hematology, serum clinical chemistry and urinalysis evaluations at termination
• Necropsies are performed on any animals that die or upon termination; weights are recorded for major organs
• Full histopathological examinations are conducted on the control and high-dose groups and on any unscheduled deaths
• Target organs are examined in the intermediate groups
• Additional recovery group with 5 males and 5 females per dose level (120 rats total). Recovery group evaluated on day 42