Additive 3 was non sensitising to guineapig skin Result: 9.2 Repeated Dose Toxicity (Hunter, 1998) Rat/Sprague-Dawley Species/strain: Treatment phase: 5/sex/dose group Number/sex of animals: Recovery phase: 5/sex/control and high dose group Oral (gavage) Method of administration: 0, 15, 150 or 1 000 mg/kg/day for 28 consecutive Dose/Study duration: days, followed by a 14 day treatment free period for animals assigned to the recovery group Nil Mortality: Clinical observations: Treatment phase: food consumption in high dose animals was generally more than control animals during treatment. There were no clinical sings attributable to treatment. Recovery phase: comparable to controls. Clinical chemistry/Haematology: Treatment phase: animals of the high dose group had higher plasma total bilirubin (6 fold increase above controls) and in males only lower plasma cholesterol concentration and slightly higher aspartate aminotransferase (AST) activity when compared to control values. The study authors suggest that the increased total bilirubin level may be due to the method of detection for bilirubin as it could be also detecting the test substance. One female of the low dose group had a significantly decreased total leucocyte count, decreased lymphocyte count, and increased neutrophil count. The study authors suggested that this variation could be because the sample was taken at necropsy. Recovery phase: significantly increased alanine transferase (ALT) activity was observed in high dose males and significantly increased alkaline phosphatase (AP) activity and inorganic phosphatase (Pi) levels were observed in high dose females. weight: Treatment phase: significantly increased adrenal and liver weights in high dose animals and low dose males, increased kidney weights in high dose males, increased thymus weights in low dose males, increased brain weights in mid dose males. Recovery phase: comparable to controls. Necropsy: Treatment phase: a large liver was noted in four of the high dose animals (3 males, 1 male), one mid dose female, and one control male. Recovery comparable to controls.
Result: Additive 3 was non sensitising to guineapig skin 9.2 Repeated Dose Toxicity (Hunter, 1998) Species/strain: Rat/Sprague-Dawley Number/sex of animals: Treatment phase: 5/sex/dose group Recovery phase: 5/sex/control and high dose group Method of administration: Oral (gavage) Dose/Study duration: 0, 15, 150 or 1 000 mg/kg/day for 28 consecutive days, followed by a 14 day treatment free period for animals assigned to the recovery group Mortality: Nil Clinical observations: Treatment phase: food consumption in high dose animals was generally more than control animals during treatment. There were no clinical sings attributable to treatment. Recovery phase: comparable to controls. Clinical chemistry/Haematology: Treatment phase: animals of the high dose group had higher plasma total bilirubin (6 fold increase above controls) and in males only lower plasma cholesterol concentration and slightly higher aspartate aminotransferase (AST) activity when compared to control values. The study authors suggest that the increased total bilirubin level may be due to the method of detection for bilirubin as it could be also detecting the test substance. One female of the low dose group had a significantly decreased total leucocyte count, decreased lymphocyte count, and increased neutrophil count. The study authors suggested that this variation could be because the sample was taken at necropsy. Recovery phase: significantly increased alanine transferase (ALT) activity was observed in high dose males and significantly increased alkaline phosphatase (AP) activity and inorganic phosphatase (Pi) levels were observed in high dose females. weight: Treatment phase: significantly increased adrenal and liver weights in high dose animals and low dose males, increased kidney weights in high dose males, increased thymus weights in low dose males, increased brain weights in mid dose males. Recovery phase: comparable to controls. Necropsy: Treatment phase: a large liver was noted in four of the high dose animals (3 males, 1 male), one mid dose female, and one control male. Recovery comparable to controls.