32 



THE TOXICITY OF CAFFEIN. 



of a much smaller dose, namely, 0.15 gram of caff ein per kilo. Moreover, macroscopical 

 examination at the autopsy of Nos. 307 and 308 failed to show any lesions which might 

 tend to lessen the resistance to caff ein. 



That a dose of 0.15 gram per kilo is therefore in all probability the minimum fatal 

 dose for the rabbit when injected into the peritoneal cavity appears from the results 

 of the experiments in series C, in which smaller doses, 0.125 gram of caffein per kilo 

 caused mild symptoms only, while 0.1 gram per kilo rarely induced any symptoms. 

 It may be remarked that the rabbits of series C were fed carrots while rabbits Nos. 307 

 and 308 received oats. Their resistance to caffein may be different, but, as was 

 pointed out in the earlier part of this investigation, diet does not seem to influence the 

 toxicity of the single dose of caffein. Doses of 150 and of 100 to 125 mg per kilo, when 

 injected into the peritoneal cavity, maybe considered, respectively, as the minimum 

 fatal and minimum toxic doses for the gray rabbit. Analysis of the experiments in 

 series D shows much greater resistance to caffein than in the other rabbits which 

 received it intraperitoneally. Thus, after the administration of 0.2 gram per kilo to 

 each of five rabbits, no effect was observed in two cases (Nos. 310, 311), while in two 

 others (Nos. 74, 75) symptoms developed, but they survived. Only one rabbit, No- 

 312, died from the effects of this dose; the autopsy showed the presence of degenera- 

 tion of the liver and petechial hemorrhages on the cortex of the kidneys in the case of 

 No. 310, which was probably the cause of death rather than the caffein. 



Two decigrams of caffein can not be considered, therefore, the fatal dose for rabbits. 

 This is further corroborated by the results obtained in experiments with larger doses. 

 Rabbit 78, which received 257 mg per kilo, failed to show any symptoms. The same 

 amount in proportion to body weight in No. 323 caused mild symptoms only, while 

 the rapid death of rabbit No. 317 after the same dose of caffein may be explained by the 

 lesion found at autopsy, thus affording additional evidence that disease may decrease 

 the resistance to caffein. It will be observed that all the members of this series were 

 young rabbits and, as will be shown later, young animals of other species are likewise 

 more resistant to caffein than adult animals. Similar results were obtained by von 

 Anrep, who observed that atropin is less toxic in young than in full-grown animals. 



Observations were also made on the diuretic effect of caffein when injected into the 

 peritoneal cavity. The results shown in the following table indicates the stimulating 

 'effect on renal secretion whether the diet consisted of oats or of carrots. The urine of 

 some rabbits contained "moderate amounts of sugar after from 0.2 to 0.15 gram of caffein 

 per kilo was given; albumen was observed in one case, but in none of the others. In 

 rabbit No. 311 albumin was found before the injection of caffein, but none in the urine 

 which was collected three hours after caffein was injected. 



Effect of caffein on renal secretion. 



NOTE. The amount pf urine secreted in three hours by control rabbits, on a carrot diet, varied between 

 35 and 50 cc, the average weight of the animals being a little above 1,600 grams. The secretion of urine 

 on an oat diet was much less for an equal period of time. 



