TOXICITY OF STRYCHNINE TO TIIK RAT. 13 



of the rats can dispose of 50 per cent ; and that only rarely does one 

 successfully dispose of 67 per cent. This was determined by in- 

 jecting a series of rats with the minimum lethal subcutaneous dose, 

 and at the end of two hours injecting those surviving with one of 

 these fractional doses. 



Coefficients of this magnitude are representative of the experi- 

 mental conditions obtained when the drug is maintained somewhere 

 near the lethal concentration, because strychnine may be found in 

 the urine of various animals for several days after similar injections 

 are made. Coefficients obtained in this manner, therefore, apparently 

 can be applied only on a relative basis. To illustrate : The average co- 

 efficient of disposal is 50 per cent the first two hours. The amount 

 disposed of the second two hours is presumably only 50 per cent of 

 the 50 per cent which remained at the end of the second hour. At 

 the end of the fourth hour, if the application of the coefficient were 

 by absolute amounts,' no strychnine w T ould be left, whereas on a 

 strictly relative basis 25 per cent would still be present. For this 

 reason halving the coefficients obtained for 2-hour periods probably 

 gives results slightly low for the first hour. The data, nevertheless, 

 illustrate the marked ability of the rat to withstand this drug, pro- 

 viding the maximum sublethal concentration is not exceeded. An 

 average rat, however, can eliminate a minimum lethal subcutaneous 

 dose with certainty in four hours (26) and presumably in three 

 hours, if the amount of strychnine is continuously kept near the 

 lethal concentration. 



Because of this rapid disposal it is possible for the rat to survive 

 many times the lethal subcutaneous dose when it is administered by 

 mouth, providing the amount present within the system at any one 

 time does not exceed the maximum sublethal dose. This also ex- 

 plains why some animals (28) are extraordinarily resistant to strych- 

 nine by mouth. In comparing the oral toxicity of strychnine in one 

 species of animals with that in another, ratios of potency of from 1 

 to 50, or even from 1 to 100, may be obtained. Analysis will show 

 that the reason for so high a ratio may be that one of the animals 

 used for the comparison is very sensitive and has an empty stomach, 

 thus requiring only a small oral dose, while the other has a full 

 stomach, retarding the absorption of the strychnine and increasing 

 from 5 to 10 times the originally high species tolerance. Ratios of 

 potency of this magnitude, therefore, must be considered as practical 

 ratios only, rather than as the true indices of species resistance. 



ABSORPTION FROM STOMACH. 



In considering previously the absorption of strychnine from the 

 stomach, the question of distinguishing between absorption by the 

 stomach of a lethal dose of strychnine in the absence of food and in 



