The chronic toxicity of quinacrine (atabrine).

Although the recent extensive use of quinacrine in the therapeutic and prophylactic treatment of malaria has focused attention on its possible chronic toxicity, no study of its lifetime effects on laboratory animals has been reported. Experiments (1, 2) conducted for shorter periods of time have shown that quinacrine can cause extensive pathological lesions in animal tissues, especially when relatively large amounts are administered. Early experiments (3, 4, 5, 6, 7) suggested and later work (8, 9, 10, 11) established the fact that an accumulation of quinacrine occurs in animal tissues. These observations indicate the possibility of damage from small dosages. Furthermore, if quinacrine is to be administered therapeutically or prophylactically over long periods of time, dietary considerations are likely to be important. Recently Scudi and Hamlin (12) reported that rats maintained on a high protein, low fat diet resisted the toxic action of quinacrine to a graater degree than those maintained on a low protein diet or a diet high in both protein and fat. Hegsted, McKibbin and Stare (13) found that’ the addition of various vitamins, yeast and protein did not prevent changes that were produced by quinacrine in animals on an already adequate diet. In the present investigation we have demonstrated differences in response to the toxic action of quinacrine when administered for the approximate lifetime of albino rats on high and low protein diets. ._