GENERAL PROPERTIES AND ACTIONS OF THE \ ENOM. 71 



long period of time, it may lead to a slight degree of fibrosis in these organs. 

 In the lungs the venom itself does not produce any distinct changes and, as 

 stated above, the pneumonic condition which has been noted is most probably 

 due to a terminal infection. In the bone-marrow, however, changes are pro- 

 duced which probably represent an effort to produce leucocytosis of the poly- 

 morphonuclear element. 



INFLUENCE OF THE METHOD OF ADMINISTRATION ON THE TOXICITY 



OF THE VENOM. 



It was possible in certain cases to determine exactly the influence that a 

 certain mode of administration of the heloderma venom might have on the 

 toxic effect, and especially upon the lethal dose of the venom. We have tested 

 the influence of injecting the venom subcutaneouslj% intravenously, intraperi- 

 toneally, and subdurally, and also of injecting it into the stomach or intestines. 



We found that the venom acts most quickly when injected intravenously, 

 and also that, when thus administered, the minimal lethal dose is smaller than 

 when administered in any other manner. When injected in this manner the 

 venom causes the death of the animal in a very short time, usually within 30 

 minutes. 



The effect of the venom appears rather more slowly when it is injected 

 intraperitoneally, and the amount necessary to cause the death of the animal 

 is distinctly larger than when injected intravenously. 



Although the subcutaneous injection of venom kills the animals rather 

 more slowly than does the intraperitoneal injection, it is probable that very 

 little difference exists between the smallest amount of venom necessary to kill 

 the animal when injected in these two different methods. As a rule, the mini- 

 mal lethal dose appears to be the same, but occasionally an animal injected 

 subcutaneously would survive the injection, whereas an animal injected in- 

 traperitoneally with a similar quantity of venom died. The most important 

 difference between the effects of injecting venom subcutaneouslj^ and intra- 

 peritoneally probably arises from the fact that the absorption of venom from 

 the peritoneal cavity is more rapid than the absorption from the subcuta- 

 neous tissues. 



When injecting venom subdurally, one difficulty to be met and overcome 

 is the probability that the injection of large quantities of fluid into the sub- 

 dural spaces may, of itself, have some injurious influence. Although we injected 

 1 e.c. of 0.85 per cent sodium-chloride solution subdurally in guinea-pigs with- 

 out producing any noticeable effects, it is possible that the injection of 1 c.c. 

 of the diluted venom solution may produce more harmful effect than the injec- 

 tion of 0.1 c.c. of pure venom solution. Indeed, our experiments would appear 

 to support this possibility. When guinea-pigs were injected subdurally with 

 venom which had been diluted (they received subdural injections of 1 c.c. of 

 fluid), they died in almost as short a time as the animals which were injected 

 intravenously, and the minimal lethal dose appeared to be approximately the 

 same whether administered intravenously or subdurally. On the other hand, 



