Subchronic toxicity experiment with rats fed a diet containing ergotamine-tartrate

In a subchronic toxicity study 4 groups of 10 Sprague-Dawley rats/group/sex received 0, 5, 20 and 80 mg ergotamine tartrate (EAT)/kg diet respectively during 13 weeks. Food intake and water intake were measured twice a week. Body weight gain was recorded weekly. After 7 weeks and 12 weeks urine and serum were sampled to measure the kidney function. After 10 weeks blood was sampled for haematological examination. At the end of the experiment blood and a small proportion of the liver were sampled for biochemical analyses. After necropsy organ weights were recorded and tissues were fixed for a complete histopathological examination. In female rats the body weight gain, and food intake were decreased at a dose level of 80 mg EAT/kg diet. The haematological examinations revealed increased RBC and PCV values in the animals of the high dose group (80 mg EAT/kg diet) only. Biochemical examination showed increased alkaline phosphatase activity, LDL-cholesterol and decreased glucose concentrations in the serum of animals of the high dose group. Urine-analyses revealed increased urine volume only in the females of the high dose group. Relative spleen and brain weights in the high dose group were higher than in the control and pituitary weight was lower in the high dose group. Macroscopical examination revealed pale thyroids and slight dilation of the uterus, haemorrhagic changes in the lymph nodes in animals of the high dose group. The only treatment-related finding in histopathology was the muscular atrophy in the caudal longitudinal muscles of the tail of animals of the high dose group. The no-toxic effect level in this experiment was 20 mg EAT/kg diet equivalent 0.9 mg ergotamine/kg bw.