RT Journal Article SR Electronic T1 THE CHRONIC ORAL TOXICITY OF CHLOROQUINE JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 147 OP 152 VO 93 IS 2 A1 O. Garth Fitzhugh A1 Arthur A. Nelson A1 Oma L. Holland YR 1948 UL http://jpet.aspetjournals.org/content/93/2/147.abstract AB 1. A two-year chronic toxicity study with rats fed diets containing from 100 to 1000 p.p.m. chloroquine showed that the toxicity of chloroquine was very slight or questionable at 100 p.p.m. and became progressively more severe with each increase in dosage. 2. There was a significant retardation of growth at a concentration of 400 p.p.m.; lower dosages produced no effect on growth. 3. A progressive increase in mortality occurred at dosage levels of 200 p.p.m. or more; the 800 and 1000 p.p.m. chloroquine caused early death of all animals. 4. The outstanding hematological change was a leukocytosis, predominantly neutrophilic. This was marked in the group on 800 p.p.m., less striking in the group on 400 p.p.m. and scarcely noticeable in those on 200 p.p.m. chloroquine. There was an increase in the hemoglobin concentration and erythrocyte counts in the rats on the 800 p.p.m. chloroquine. 5. Histopathological changes increased from very slight or absent in rats on 100 p.p.m. to marked in those on 800 and 1000 p.p.m. The two prominent lesions at toxic dosages of chloroquine were a slow focal necrosis of striated muscle, especially cardiac, and a moderate degree of centrolobular hepatic necrosis and fibrosis. 6. In relation to body weight of the rat the lowest dosage of chloroquine which produced slight toxic effects in some animals corresponds to approximately 4 mgm./kgm./day for two years. 7. In comparison with quinacrine fed to rats at similar dosage levels and with a similar diet, the anatomical changes produced by chloroquine were similar; however, the toxicity of chloroquine was, on the whole, slightly less than that of quinacrine. At the low dosage level of 4 mgm./kgm./day there was no noticeable difference between the toxicities of the two substances.