10 THE TOXICITY OF CAFFEIN. 



Stuhlmann and Falck 83 (1857) were the first to make a study of 

 the toxicity of caffein on animals of different species. The adminis- 

 tration of 0.5 gram of caffein subcutaneously or per rectum in rabbits 

 induced tremors, tonic and clonic convulsions, paralysis, and increased 

 frequency of respiration at first followed by violent dyspnoea. On 

 autopsy he noticed congestion of the organs and in two of the three 

 rabbits experimented upon punctiform hemorrhages of the brain with 

 congestion of the meninges were found. In the other rabbit anemia 

 of the brain was observed. Experiments on cats were carried out 

 by subcutaneous, intravenous, and rectal injections. The symptoms 

 observed after the administration of *0.5 to 0.7 gram of caffein were 

 the same as in rabbits except that the cats developed diarrhea when 

 caffein was given and no anatomic lesions were found on autopsy. 

 The effect of caffein on dogs indicated that in subjects of medium 

 weight a dose of 0.5 gram given by mouth might produce restlessness 

 and increased frequency of respiration, while the injection of the 

 same amount intravenously into such animals may cause death. 

 Large, full-grown dogs, however, survived an intravenous injection 

 of 2 grams of caffein, showing symptoms of incoordination, salivation, 

 and frequent defecation. These investigators also made observations 

 on caffein, using pigeons and other birds; 0.5 to 0.1 gram introduced 

 into the stomach caused vomiting, diarrhea, tonic, but more fre- 

 quently clonic, convulsions, incoordination, tremors, paresis, and 

 paralysis. 



In a few, but not in all of the birds, there was at first increased 

 frequency of respiration followed by dyspnoea and circulatory dis- 

 turbances. These amounts of caffein proved fatal in all of the experi- 

 ments on birds. Inflammation of the intestinal mucosa and conges- 

 tion of the meninges were the only changes found on autopsy. 

 Stuhlmann and Falck also studied the effects of caffein on fishes and 

 toads. Mitscherlich 60 (1858) fed 0.4 gram of caffein with bread to a 

 rabbit and noticed lowered temperature, fatigue, convulsions, first 

 increased then decreased frequency of respiration, and on autopsy 

 congestion of all the viscera. He also reported observations on two 

 frogs, one of which was given one-sixteenth of a grain of caffein in a 

 pill with bread. It was administered to the other frog in aqueous 

 solution, but the mode of administration was not published. The 

 symptoms observed were in the main the same as in rabbits. In 

 pigeons 0.125 gram introduced into the stomach caused severe vomit- 

 ing, muscular incoordination, tonic rigidity of the limbs, and retrac- 

 tion of the head. Respiration was increased in frequency. Death 

 followed within 3 hours and 15 minutes. 



From a series of experiments on frogs which Hoppe 38 carried out 

 (1858) by applying one-fourth of a grain of caffein to the muscles of 

 the back, he concluded that caffein causes paralysis of the nerves, 



