ACUTE INTOXICATION GUINEA PIGS. 47 



Experiments were also conducted to determine the largest dose which does not pro- 

 duce any visible effects. In a number of testa with from 100 to 120 mg caffein per 

 kilo (series E, see Table 6, p. 51) no manifestation of nervous or muscular disturbance 

 nor any departure from the normal in respiratory activity was observed. Such 

 quantities may be regarded as the largest doses which are surely safe for these animals. 

 It is quile possible, therefore, that the greater variation in the toxicity of caffein 

 observed in these experiments is due to morbid conditions. Moreover, there is some 

 evidence that caffein increases the toxicity of certain poisons, as shown by Hale 33 for 

 acetanilid. Is it not possible that caffein may similarly be affected by poisons cir- 

 culating within the body? Indeed the recent work of Loeb w makes this supposition 

 highly probable. This investigator found that caffein and adrenalin injected together 

 produce myocarditis in the rabbit. It is conceivable that the combined action of 

 caffein and some preexisting poison may cause changes which terminate in the death 

 of the animal. The delayed death of guinea pigs after the administration of caffein 

 observed in this and other series may probably be accounted for in this way. 



Experiment 57 lends some support to this view. The condition of the kidneys and 

 the presence of a severe gastro-enteritis are sufficient to account for the death of this 

 case. Again the frequent association of gastro-enteritis and congestion of the organs 

 in caffein intoxication iound in different animals makes it highly probable that these 

 lesions were caused by caffein. 



INJECTION INTO THE PERITONEAL, CAVITY. 



The experiments were carried out with different doses. All the guinea pigs in 

 this series were kept on a uniform diet, consisting of oats . Most of them were of average 

 size and there were no wide variations in their weights. The experiments of series A 

 with the smallest doses were conducted in March and April; all the other experiments 

 it will be noticed were made in October. 



SERIES A. 



Guinea pig 41. Weight, 700 grams. Diet, oats. 



April 1: 3.30 p. m., 4.5 cc 2 per cent caffein (130 mg per kilo) injected into peri- 

 toneal cavity. 5.35 p. m., symptoms present but no tetanus. 



April 2: Found dead about 2 p. m., duration of life about 22 hours. Autopsy: 

 Subcutaneous hemorrhage at the point of inoculation; serious exudate on visceral 

 and parietal peritoneum with marked inflammation of peritoneum; portions of 

 intestines showed slight enteritis. 



Guinea pig 49. Male. Weight, 370 grams. Diet, oats. 



April 1: 3.15 p. m., 2.5 cc 2 per cent caffein (135 mg per kilo) injected into the peri- 

 toneal cavity; 5.30 p. m., symptoms present; reflexes increased, but no tetanus. 

 Guinea pig survived. 

 Guinea pig 47. Female. Weight, 550 grams. Diet, oats since about February 4- 



March 17: 3.30 p. m., 3.5 cc 2 per cent caffein (127 mg per kilo) injected into peri- 

 toneal cavity; 4.35 p. m., increased irritability present, but not marked; 5.40 p. m., 

 symptoms about the same as before. 



March 18: 2.30 p. m., condition good; no symptoms. Survived. 

 Guinea pig 50. Female. Weight, 290 grams. Diet, oats. 



April 1: 3.30 p. m., 2 cc 2 per cent caffein (138 mg per kilo) injected into peritoneal 

 cavity; 5.35 p. m., symptoms present; reflexes much increased, but no tetanus. 

 Survived. 



SERIES B. 



Guinea pig 51. Yellow female. Weight, 41.5 grams. 



October 1: 9.50 a. m., 3 cc (144 mg per kilo) 2 per cent caffein injected into peri- 

 toneal cavity; 4.30 p. m., no symptoms, although under observation all day. 



October 3: 2 p. m., alive. 

 Guinea pig 52. White male. Weight, 450 grams. 



October 1: 9.45 a. m., 3.5 cc, 2 per cent caffein (155 mg per kilo), injected into 

 peritoneal cavity; 4.30 p. m., no symptoms developed since injection. 



October 3: 2 p. m., alive. 



