496 Proceedings of the Royal Society of Edinburgh. [Sess. 
percentage of chloroform in the arterial blood than does the administration 
of the same amount hypodermically ; and hence dogs which got two doses 
of 25 c.c. of chloroform by the mouth may have had a higher proportion of 
the drug in the circulating blood than those which had two doses of 5 c.c. 
hypodermically. The respect in which the hypodermic administration re- 
sembles the administration by the mouth is in the persistence of the drug. 
The hypodermic administration of chloroform to rabbits appears to be 
almost as fatal as the administration by the mouth, and the appearance of 
proteins and tube-casts in the urine is almost as frequent. Dr Clark also 
finds that the changes in the liver are as marked as when the drug is given 
by the stomach. 
It would seem that the acute transitory action of chloroform adminis- 
tered by the respiratory passages leads to a stimulation of hepatic 
metabolism, while the less acute and more sustained action leads to injury 
without previous stimulation. 
Although in these experiments the administration of chloroform by the 
respiratory passages failed to cause the grave disturbances, metabolic and 
structural, which were caused by its administration by other channels, the 
results of such administration by other channels seem to show how, in the 
event of the chloroform given by the lungs not being eliminated with the 
usual rapidity, serious injuries might be effected, which would lead to the 
symptoms of late chloroform poisoning. 
Moore and Roaf ( B.M.J . , vol. ii., 1906, p. 721) have shown how 
chloroform is fixed to the proteins of the blood, and Nicloux ( G.R . Soc. 
biol., t. lx., pp. 206, 248, 1906 ; t. lxii., p. 1153, 1907) has also shown 
the way in which it is anchored to certain tissues. Sherrington and 
Sowton have proved that the action of chloroform upon the heart depends 
upon its tension in the circulating fluid, and that it is greater in saline 
solutions than in the protein-containing blood where it becomes fixed. 
These observations, taken in conjunction with our results, seem to show 
that chloroform, when given by the respiratory passages, is rapidly taken 
up and first dissolved in the blood, and in this condition acts upon the nerve- 
centres, the excess being rapidly eliminated ; while, when given by the 
stomach or hypodermically, the assumption is slow, more stable compounds 
are formed, the elimination is consequently delayed, and the drug has thus 
more time to produce a slow toxic effect upon the protoplasm of the tissues. 
The onset of late chloroform poisoning after anaesthesia would thus be 
due to delayed elimination brought about by unusually firm fixation, or by 
respiratory deficiency. 
{Issued separately August 15, 1908.) 
