There was a suggestion of decreased food consumption in the male dogs at 200, 450 and 1,000 mg/kg and in females dogs at 200 and 450 mg/kg. Food consumption was variable and certainly influenced by the frequent vomiting observed in the high-dose group (both sexes). The 200 and 450 mg/kg male dogs appeared to have decreased growth rate as a percent increase in body weight compared to Day 0 control weights in the 200 and 450 mg/kg dogs. This was not a dose-related trend, however the 1,000 mg/kg dog was vomiting frequently enough to have likely reduced the absorbed dose to a disproportionate level. Likewise in females, there was a suggestion of apparent decrease in growth rate as a percent increase in body weight compared to Day 0 control weights in the 200, 450 and 1,000 mg/kg dogs. The incidence of vomiting in the 1,000 mg/kg female likely reduced the absorbed dose to a disproportionate level. There was an apparent increase in vomiting in the 1,000 mg/kg dogs during treatment, which likely influenced the absorbed dose of compound. There was an increase in salivation priorto dosing in the 450 and 1,000 mg/kg dogs. This would appear to have been due to the physical effect of the test solution rather than a systemic neurologic response since no other relevant clinical signs or observations were detected. In addition there were no neurology or ophthalmology findings attributed to treatment. There was a preliminary suggestion of decreased thyroxine (T4) relative to pretreatment, as part of a dose- response manner and/or with reference to historical controls in the 50, 200, 450 and 1,000 mg/kg females on Days 15 and 24; in the 200, 450 and 1,000 mg/kg males on Day 15 and 24. There was a preliminary suggestion of increased ALP in the 450 and 1,000 mglkg females and males on Days 15 and 24. There was a preliminary suggestion of increased ALT in the 450 and 1,000 mg/kg females and the 1,000 mg/kg males on Days 15 and 24. There was a suggestion of increased cholesterol in the 200, 450 and 1,000 mg/kg females on Day 24, and in the 1,000 mg/kg females on Day 15. There was no change in inducible enzymes (demethylases or UDP-GL). There were no outstanding features of the hematology or urinalysis profiles. There were no compound-related gross pathology lesions. There was a preliminary suggestion from early examination of the relative organ weights that the relative liver weights were increased in at least the 450 and 1,000 mg/kg male and female dogs, and relative thyroid weights were increased in the 1,000 mg/kg female dog. Micropathology changes consisted of nephrosis in the kidneys, with some sclerosis and oxalate deposition. Both sexes were affected at 450 and 1,000 mg/kg, and the male also showed lesions at 200 mg/kg. In more severe cases in the tubular epithelium, there was occasional hyperplasia with bizarre nuclei, occasional mitotic figures and distorted cell shape and size. Hepatic changes consisted of bile stasis in 450 and 1,000 mg/kg females and increased cytoplasmic granularity in hepatocytes from the 450 mg/kg male.