Table 7.

Repeated dose intravenous toxicological studies in dogs and monkeys

Species (number of animals per group)	Dosage (mg/kg bw per day)	Observation (days)	Adverse effects	NOAEL emesis (mg/kg bw per day)	NOAEL haemato‐ toxicity (mg/kg bw per day)	Reference
Dog (1 male, 1 female)	4 weeks 0.02, 0.06 and 0.18	28	Emesis, bloody stool and weight loss, blood disorders lymphopenia and erythroblastosis	0.02	0.02	Stähelin (1968)
Beagle Dog (1 male, 1 female)	5 daily injections 0, 0.016, 0.031, 0.063, 0.125, 0.25	52	Leucopenia, neutrophilia and lymphopenia were described as emesis, erythema and polydipsia	0.031	0.016	IRDC report (1973)
Beagle Dog (1 male, 1 female)	5 daily injections three times with 9 days of rest0.031, 0.125	75	Leucopenia, neutropenia, relative lymphocytosis, thrombocytopenia, polychromasia of erythrocytes	0.031	[LOAEL 0.031]
Beagle Dog (1 male, 1 female)	Weekly injection during 6 weeks 0.031, 0.063, 0.125, 0.25	43, 81	Emesis and slight erythema post‐dosing, neutropenia, anaemia, lymphopenia	0.031	[LOAEL 0.031]
Rhesus Monkey 1 male and 1 female/group	5 daily injections 0,0.125,0.25, 0.50, 1.0	12, 50	Emesis, polydipsia, diarrhoea, erythema, increased haematocrit, anaemia, leucocytosis and/or leucopenia, neutrophilia, lymphopenia, elevated ALT and AST activity, elevated BUN and nucleated erythrocytes	0.125	0.125	IRDC report (1973)

ALT: alanine transaminase; AST: aspartate aminotransferase; NOAEL: no‐observed‐adverse‐effect level; BUN: blood urea nitrogen; LOAEL: lowest observed adverse effect level.