950 
Journal of Agricultural Research 
Vol. XXX, No. 10 
its solubility in and absorption from 
the digestive tract are matters of some 
little interest in connection with our 
study of an even more insoluble 
chlorine compound. Hall (6) pointed 
out in his first paper that the safety of 
carbon tetrachloride appeared to be 
correlated with its insolubility. Chopra 
and Me Vail (4) sav: “Owing to its low 
solubility and volatility and conse¬ 
quently slow rate of diffusion, only 
small quantities are absorbed into the 
circulation. Large quantities can there¬ 
fore be introduced into the alimentary 
canal without untoward effects.” So 
far as we can judge from the available 
evidence, the amount of absorption of 
carbon tetrachloride from the digestive 
tract does not usually increase as the 
amount administered is increased, or 
if it does, there seems to be a com¬ 
pensatory elimination of the larger 
amounts of the drug without a con¬ 
comitant and strictly proportionate 
increase in liver injury. Wells (11) 
has recently shown that a high per¬ 
centage of the absorbed carbon tetra¬ 
chloride is rapidly excreted in the 
expired air. 
The experience of various workers 
indicates that a certain amount of drug 
is absorbed usually and that it causes a 
moderate amount of injury to the liver, 
this injury being rapidly and completely 
repaired. In fact, Bose and Mukerji 
( 1 ) have reported two cases in which a 
levulose test of liver function before 
and after treatment with carbon tetra¬ 
chloride showed deficiency of liver 
function before treatment and normal 
function after treatment, a thing theo¬ 
retically possible where a chronic indo¬ 
lent pathological condition is rendered 
acute and stimulated to repair. When 
large amounts of the drug, 25 c. c. per 
kilo, or totals of several hundred c. c. 
at a time, or up to 2 liters in repeated 
doses, are administered to dogs, as has 
been done, it seems clear that if the ab¬ 
sorption and a concomitant liver injury 
increased proportionately these animals 
would be killed in all cases, as we 
know that animals may be killed with 
therapeutic doses if conditions are such 
as to facilitate absorption, for instance, 
such conditions as appear to be present 
in certain cases of hemorrhagic enter¬ 
itis. However, normal dogs commonly 
survive these heavy doses, showing 
that absorption or the tissue injury 
from the absorbed drug is limited; 
almost all the deaths reported in 
man and dogs followed therapeutic 
doses. 
Lamson, Gardner, Gustafson, Maire, 
McLean and Wells (9) report that of 
35 dogs given 100 to 500 times the 
therapeutic dose only 1 died. To put 
it in other words, there is no such thing 
as a minimum lethal dose of carbon 
tetrachloride for such animals as man 
and dog, and the same is true for 
chickens. Individuals of high indi¬ 
vidual intolerance for the drug may be 
killed with therapeutic doses, but 
normal individuals will tolerate enorm¬ 
ous doses, and the limit of tolerance for 
normal dogs appears to be approxi¬ 
mately the limit of gastric capacity. 
Chloroform, a much more soluble 
product, soluble 1 part in 161 parts of 
water at 22° C., is apparently much 
more readily and regularly absorbed 
in the digestive tract than is carbon 
tetrachloride, or a resultant injury is 
more regularly produced. Caius and 
Mhaskar (2) state in regard to chloro¬ 
form: “Toxic symptoms are occa¬ 
sionally noticed with a dose of 30 
minims [2 c. c.] and become more 
general and more marked with in¬ 
creasing dosages until 45 minims 
[3 c. c.] is reached.” A dose of 3 c. c. 
of carbon tetrachloride is the one 
most used for human adults and 
usually causes no symptoms or only 
slight and transient symptoms. Much 
larger doses have been administered 
without evident bad effects. Peyre 
(10) has reported no inconvenience from 
carbon tetrachloride in a case of 
hepatic cirrhosis with ascites, precisely 
the sort of case in which bad results 
would follow if absorption and pro¬ 
portionate injury occurred to any 
marked extent. 
Reasoning from the increased efficacy 
and safety of carbon tetrachloride as 
compared with chloroform, and asso¬ 
ciating it with its lesser water-solubility 
as perhaps the determining factor for 
these qualities, the writers have raised 
the question as to whether a halogen 
compound less soluble than carbon 
tetrachloride might be still more ef¬ 
fective against hookworms, or safer, or 
more effective and safer. Carbon 
trichloride is evidently a less soluble 
halogen compound. The following ex¬ 
periments were made to test it. 
EXPERIMENTAL DATA 
COARSE CRYSTALS ADMINISTERED IN 
CAPSULES 
Six dogs were given the coarse crys¬ 
tals in capsules, the number of each 
dog, its weight, its total dose, and its 
dose rate in terms of grams per kilo 
(g. p. k.) being as follows: Dog. No. 
665, 13 kilos, 1 gm. (0.077 g. p. k.); 
No. 666, 10 kilos, 2 gm. (0.2 g. p. k.); 
No. 667, 6.5 kilos, 3 gm. (0.46 g. p. k.); 
