Minimal Lethal Dose of various Toxic Substances. 323 



tion in the plasma of any substance administered to animals under like 

 conditions in doses proportional to their body weights will be much less 

 in the lighter animals than in the heavier individuals of the same species. 



On the other hand, if the doses be administered in relation to the body 

 surface, their initial and their maximal concentration in the plasma will 

 be the same whatever be the weights of the individual animals concerned. 



The results brought forward for diphtheria toxin do not constitute an 

 isolated instance in support of this view, that in any given species of 

 animal dosage must be used in relation to the volume of the blood. Very 

 numerous observations from the literature of toxicology which we have 

 collected and analysed confirm the accuracy of this method of measure- 

 ment. It appears to hold, so far as we have been able hitherto to ascertain, 

 for a large number of substances of very different constitution and of 

 diverse mode of action in warm-blooded animals. Wherever a sufficient 

 number of accurate data can be found the effect of dosage can be shown 

 to be related to blood volume and surface area in any given species. 

 Numerous results which have been thought to be inexplicable when the 

 dosage was expressed in per cent, of body weight, except on the ground 

 of special individual susceptibility or individual resistance, in reality give 

 precisely the results which would have been expected had the dosage been 

 expressed in terms of body surface. 



In the case of arsenic (AS2O3) in the rabbit the observations of 

 Morishima (8) afford an interesting illustration. The data and the calcula- 

 tions from these observations are given in Table III. Here it is seen that 

 the time of death shows no exact relation to the dose expressed in per 

 cent, of weight, but it follows quite closely the dose in relation to surface, 

 though animal 5 shows an irregularity in living longer than animal 4. 

 It will, however, be seen that the average dose per surface of animals 3 

 and 5, taken together, and their average time of death are identical with 



Table III. — -Arsenic (AS2O3) in Babbit, Morishima's Experiments 

 (subcutaneous injection). 



No. 



Weight 

 of animal, 

 in grin. 



Actual dose 

 (d), in ingrm. 



Dose (D) in 

 relation to surface, ' 

 in mgrm. 

 D = d/W"-' 2 . 



No. 

 of hours to 

 death. 



Dose in per 

 cent, of weight, 

 mgrm. 

 per 100 grm. 



1 



1324 



8 -61 



4-86 



00 



0-65 



2 



1103 



7 72 



4-95 



00 



0-70 



:i 



1495 



10 -47 



5 -42 



84 



0-70 



4 



1112 



8 -90 



5 -G7 



96 



-80 



5 



1702 



11 -90 



5 -91 



108 



0-70 



