TOXICITY OF STRYCHNINE TO THE RAT. 17 



SUMMARY. 



The limit of tolerance of Mux uorvegicus 10 to strychnine admin- 

 istered subcutaneously is from 3 to 3.5 milligrams of strychnine sul- 

 phate per kilo. Of the comparatively few species of mammals for 

 which accurate data are available, the guinea pig alone possesses a 

 resistance greater than this. The existing data indicate that while 

 the lower orders of mammals, such as the Chiroptera (bats) (24) and 

 Insectivora (hedgehog) (19) (39), are at times more tolerant than 

 the guinea pig and the rat, at other times they are less tolerant. 



The size of the subcutaneous lethal dose (species tolerance) remains 

 constant when a certain definite experimental procedure is followed. 

 General or mixed diets and seasons had no effect upon the species 

 tolerance in the series of experiments reported in this bulletin. 



The rat shows a marked ability to dispose of strychnine. Under 

 favorable conditions the calculated disposal amounts to 1 milligram 

 per hour (one-third of a minimum lethal subcutaneous dose). Prac- 

 tically, with the unfavorable experimental procedure used (discon- 

 tinuous injections) it was slightly less than this. 



Immature rats differ from adult rats, both in the toxicity of and 

 reaction to strychnine, which seems to be correlated with the func- 

 tional development of their nervous system. 



The practically certain oral lethal dose of strychnine is from 20 

 to 25 milligrams per kilo of the free alkaloid, equivalent when cal- 

 culated as the sulphate to from 25.6 to 32 milligrams. The ratio of 

 the subcutaneous lethal doses to the oral lethal doses is about 1 to 

 8 or 1 to 9. The reason for this high ratio in rats would seem to be 

 that when less than a lethal dose has been given the stomach and its 

 contents directly or indirectly hinder absorption. On this account 

 the animal can prevent the accumulation of a lethal amount within 

 the system by the rapid disposal. When a lethal dose is administered 

 by mouth the fatality usually occurs within several hours. The rat, 

 therefore, must be overwhelmed by the drug; otherwise, it probably 

 will survrce. At times this certainly involves the play of a usually 

 subordinate function, gastric absorption. 



On the basis of its alkaloid content, the toxicity of two so-called 

 tasteless preparations of strychnine (adsorption compound of dia- 

 tomaceous or infusorial earth with strychnine sulphate) was found 

 to be reduced by more than 50 per cent. 



Mice are more susceptible to strychnine than rats, both to subcu- 

 taneous injections and to doses orally administered. 



10 It is to be hoped that the first opportunity presenting itself for a comparative test 

 with Mus rattus will be accepted by those into whose hands these data fall. The sup- 

 position that the toxicity of strychnine will be the same in both cases is not warranted, 

 although it is legitimate to infer that this is true in the case of barium carbonate. 



