control: 0 mg.kg-1.day-1 low dose: 150 mg.kg-1.day-1 mid dose: 400 mg.kg-1.day-1 high dose: 1 000 mg.kg-1.day-1 an additional satellite group of 10 animals (5/sex) included in the control and high dose groups were maintained for a further 14-day recovery period prior to sacrifice mid and low dose animals showed no of Clinical observations: toxicity during the study; high dose animals of both sexes showed isolated incidents of increased salivation after day 5, together with fur wetting and red/brown staining of the external body surface; one high does female developed hunched posture, pilo- erection, decreased respiratory rate, lethargy and ptosis by day 27; following dosing, deterioration continued and the animal was killed in extremis showed increases in plasma alkaline phosphatase; Clinical male animals in this group showed increases in aspartate aminotransferase and bilirubin while both cholesterol and triglycerides were slightly elevated in females; plasma alanine aminotransferase was mid and low dose also slightly raised in all animals in the high dose animals showed no group; treatment-related changes had regressed treatment- related completely after 14 days without treatment; all high- changes in blood dose animals showed a reduction in haemoglobin chemistry or concentration and haematocrit; reductions in mean haematological corpuscular haemoglobin and mean corpuscular parameters; high dose volume suggest that the anaemia was microcytic and animals of both sexes hypochromic in nature; cessation of treatment and mid- dose males resulted in complete recovery by day 14 absolute and relative liver weight compared with Terminal studies, controls; several animals had a pale liver at the end including histopathology: of the treatment period; treatment-related hepatic changes were observed including hepatocyte high dose animals of both enlargement and increased hepatocytoplasmic sexes had a statistically density but no evidence of hepatocellular significant increase in both degeneration; the brain and kidney
control: 0 mg.kg-1.day-1 low dose: 150 mg.kg-1.day-1 mid dose: 400 mg.kg-1.day-1 high dose: 1 000 mg.kg-1.day-1 an additional satellite group of 10 animals (5/sex) included in the control and high dose groups were maintained for a further 14-day recovery period prior to sacrifice Clinical observations: mid and low dose animals showed no of toxicity during the study; high dose animals of both sexes showed isolated incidents of increased salivation after day 5, together with fur wetting and red/brown staining of the external body surface; one high does female developed hunched posture, pilo- erection, decreased respiratory rate, lethargy and ptosis by day 27; following dosing, deterioration continued and the animal was killed in extremis Clinical mid and low dose animals showed no treatment- related changes in blood chemistry or haematological parameters; high dose animals of both sexes and mid- dose males showed increases in plasma alkaline phosphatase; male animals in this group showed increases in aspartate aminotransferase and bilirubin while both cholesterol and triglycerides were slightly elevated in females; plasma alanine aminotransferase was also slightly raised in all animals in the high dose group; treatment-related changes had regressed completely after 14 days without treatment; all high- dose animals showed a reduction in haemoglobin concentration and haematocrit; reductions in mean corpuscular haemoglobin and mean corpuscular volume suggest that the anaemia was microcytic and hypochromic in nature; cessation of treatment resulted in complete recovery by day 14 Terminal studies, including histopathology: high dose animals of both sexes had a statistically significant increase in both absolute and relative liver weight compared with controls; several animals had a pale liver at the end of the treatment period; treatment-related hepatic changes were observed including hepatocyte enlargement and increased hepatocytoplasmic density but no evidence of hepatocellular degeneration; the brain and kidney
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