494 Proceedings of the Royal Society of Edinburgh. [Sess. 
now being investigated by Dr Clark. The effect upon the kidney, as 
indicated by the presence of protein and the appearance of renal epithelium 
in the urine, is much more marked when chloroform is given by the mouth 
than when administered by the respiratory passages. Zweifel {fieri, klin. 
Wochensch., 1874, p. 245) and Pohl (Arch. f. exp. Path. n. Pharmac., 
Bd. xxviii., p. 251) found traces of chloroform in the urine, and Nicloux 
(Jour, de Pharm. et Ghim.. 24 [6], p. 64) has found that the amount 
after administration by the respiratory passages is very small. But the 
fact that protein appeared in the urine in certain of my experiments in 
which it was given in this way without exerting a true toxic action on the 
liver, and the very frequent occurrence of transient albuminuria described 
by many surgeons, seems to indicate that its effect on the kidney is direct. 
The question naturally arises of how far these differences in the effect 
of chloroform given by the respiratory passages and by the mouth are 
merely a result of difference of dose. The amount of chloroform in the 
blood necessary to produce anaesthesia has now been investigated by 
several observers — Tissot (C.R. Soc. biol., 1906, p. 198), Nicloux (C.R. Soc. 
biol ., t. lx., p. 144), Buckmaster (Proc. Roy. Soc., vol. lxxix., 1907) — and 
the general result is to indicate that, to produce the state, something like 
30 to 50 mg. per 100 c.c. must be present in the blood of the dog or cat. 
After the administration is stopped, the amount rapidly falls, and the elim- 
ination is practically complete in about three hours (see succeeding paper). 
So far no determinations of the amount of chloroform in the blood after 
it has been administered by the mouth have been recorded, but a series of 
experiments carried out by Miss D. Lindsay upon the blood of rabbits 
after the administration of chloroform in oil, nearly equivalent to that 
given by me to the dogs experimented upon, shows that the percentage 
amount never rises so high as during administration by the lungs, and that 
the drug persists in the blood for a much longer period — about six hours. 
The greater effect upon the metabolism of chloroform when adminis- 
tered by the mouth is not the result of a larger dose, but must be due 
rather to the direct influence upon the liver, and to the more prolonged action. 
In rabbits, I have found that the administration of 1 c.c. by the 
mouth, which leads to the appearance of at most between 20 and 30 mg. 
per 100 of CHC1 S in the blood, is infinitely more toxic than a prolonged 
administration by the lungs. Of 12 rabbits, no less than 11 showed 
albuminuria, while 7 died, and 2 which appeared to be dying were killed. 
How far the fatal result is due to the injury to the kidneys, how far 
to the toxic action on the liver, and how far to the more general injury to 
the tissues produced, we have no data to enable us to determine. The 
