ACUTE INTOXICATION RABBITS. 37 



doeee were administered by injection into the lumbar muscles the appearance of 

 symptoms was delayed several hours in some cases. The duration of life in these 14 

 rabbits varied considerably. Eight of them died within 1 to 20 hours; six survived. 

 About 0.2 gram caffein per kilo may be regarded as the minimum fatal dose, while 

 the minimum toxic dose is somewhere between 130 and 150 mg per kilo. 



INTRAVENOUS INJECTION. 



These experiments were carried out on well-fed, full-grown gray rabbite. The diet 

 for several days preceding the experiments consisted of oats or carrots, which were given 

 ad libitum. The injections were made into the ear veins from a burette or by means 

 of a syringe, the temperature of the caffein solution being about 40 C. Attention 

 was also directed to the effect of the rate of injection and of the concentration on the 

 toxicity. The minimum toxic as well as lethal doses were determined as shown in 

 the following experiments. 



SERIES A. 



In these experiments the rate of injection was about 1 cc of 2 per cent caffein solution 

 per minute. 

 Rabbit 194. White, female. Weight, 1,310 arams. 



October 19: Injected 7.5 cc 2 per cent solution caffein (115 mg per kilo) into the ear 

 vein. Rabbit showed stiffness ; paralysis of extremities appeared soon after. Rabbit 

 survived. 

 Rabbit 556. Gray, female. Weight, 1,635 grams. 



January 31: 2 p. m., 11 cc 2 per cent caffein (134 mg per kilo) injected into ear vein, 

 in about 11 minutes; 2.10 p. m., convulsions, rabbit remained lying on its side; during 

 the rest of the hour it had convulsions occasionally; 3.20 p. m., convulsions and died. 

 Rabbit did not urinate after the injection of caffein. 

 Rabbit 657. Gray, female. Weight, 1,580 grams. 



January 31: 2.30 to 2.37 p. m., 7 cc 2 per cent caffein injected from the burette at 

 the rate of 1 cc per minute; 2.37 p. m., now of liquid ceased, veins were engorged and 

 bled freely, injection was continued by means of a syringe; 2 cc 2 per cent caffein 

 injected in two minutes; injections discontinued as convulsions appeared; 2.50 p. m., 

 rabbit raised itself but fell over; 3.10 p. m., rabbit assumed normal attitude, walked 

 about the floor without manifesting any signs of the effects of caffein; 4.30 p. m., 

 walked about, gait normal, condition seemed to be good. 



February 1: 2p.m., condition good, appetite good, total amount of caffein injected, 

 9 cc 2 per cent solution, or 114 mg per kilo. 

 Rabbit 558. Gray, female. Weight, 1,590 grams. 



January 31: 3 p. m., given 8 cc 2 per cent caffein in eight minutes; 3.10 p. m., 

 violent convulsions; 3.20 p. m., rabbit was stretched out on his abdomen, extremities 

 extended, urinated; 4.30 p. m., looked normal; was able to walk about. 



February 1: 2 p. m., condition good, appetite good. 

 Rabbit 292. Belgian hare, male. Weight, 1,770 grams. 



February 18: 4.26 to 4.39 p. m., 12.5 cc warm caffein solution (0.141 gram per kilo) 

 injected into ear vein, convulsion followed when this quantity was injected, tonic 

 rigidity of limbs followed soon after; 4.52 p. m., condition unchanged, rabbit on floor, 

 limbs stretched out, and lying on abdomen. 



Rabbit 294. Belgian hare, female. Weight, 1,350 grams. Carrot diet for about 10 days 

 before the experiment. 



February 19: 12.20 p. m., 5 cc 2 per cent caffein (74 mg per kilo) injected into 

 ear vein in five minutes, edema of the ear, other ear used, 3.5 cc injected in 10 min- 

 utes, repeated convulsions; 1.25 p. m., rabbit still alive, frequent attacks of convul- 

 sions; 2.30 p. m., found dead. Total amount injected in 15 minutes, 8.5 cc, or 0.126 

 gram per kilo. 



It will be observed in the preceding experiments that symptoms of severe intoxi- 

 cation were present in all of the six rabbits, but only two of these (Nos. 294 and 556) 

 died from the effects of caffein. Of those which survived, three received doses of 



a Time of Injection Inadvertently omitted, but was probably not slower than In the other cases of this 



