Abstract

In rats acetanilid in doses of 19 and 38 mgm. per kilogram of body weight (minimum therapeutic antipyretic dose = 12.5 mgm. per kilogram (11)) six times a week for 13 weeks did not produce significant changes in the growth, food consumption, hemoglobin concentration, number of erythrocytes, leucocytes, or ratio of types of leucocytes.

Rats receiving doses of 200 mgm. acetanilid per kilogram (50 per cent "fatal" single dose = 800 mgm. per kilogram (11)) six times a week for 10 weeks were likewise not found to be significantly different from normal animals.

Twenty-six rats were given 400 mgm. acetanilid per kilogram, some of them being continued for as much as 13 weeks. During this time 9 of them died. The average duration of life at this dosage was not determined, but was at least 70 days. The animals grew more slowly than normal animals and at 6, 10 and 13 weeks the hemoglobin concentration and number of erythrocytes were significantly lower. No changes were observed in the leucocytes. At the end of ten weeks the number of reticulocytes was several times that of normal animals (S.R. = 8.6).

Nine rats that received 400 mgm. per kilogram for 13 weeks were studied for 4 weeks after withdrawal of the drug. At the end of this time they were growing at more than the normal rate and the hemoglobin, erythrocytes and reticulocytes were at approximately normal level.

The fall in temperature in these withdrawn animals after a subsequent large single dose of acetanilid was not significantly different from that in normal animals.

These results show that more than one-fourth of the acute fatal dose of acetanilid must be given daily in order to produce signs of chronic toxicity. Such doses are many times larger than the dose necessary to produce therapeutic effects in these animals.