11 
trile with the formation of methyl alcohol on the one hand and hydro- 
cyanic acid on the other, according to the equation 
CH3CN + H3O = CH3OH + HCN. 
Such a reaction has not been obtained by chemical processes outside 
of the body, and we have no reason to suppose that it can occur within 
the body.® A study of a number of related nitriles led me to form 
another conception of the process by which the hydrocyanic acid is 
formed. On comparing the toxicity of a number of nitriles I noticed 
that there is a relation between the degree of toxicity and the ease 
with which the hydrocarbon residue, to which the cyanogen group is 
lunited, is oxidized in the body. Thus acetonitrile is the least poison- 
ous of the series of aliphatic nitriles studied ; the methyl group is the 
most difficult of the hydrocarbon residues in these compounds for 
the body to oxidize. Proprionitrile (C2H5CN) is many times more 
poisonous than acetonitrile; the ethyl group (CgH.) is readily oxidized 
in the body. After the administration of acetonitrile, formic acid 
(a product of the oxidation of the methj^l group) is found in the urine; 
this shows that the oxidation is incomplete; after proprionitrile, the 
urine contains no formic (or acetic) acid, the ethyl group having been 
completely oxidized. The difference in the ease of oxidation of the 
methyl and ethyl groups is most strikingly illustrated by the fate in 
the body of ethyl and methyl alcohol, respectively. Ethyl alcohol, 
even when administered in comparatively large doses to man or other 
animals, is completely oxidized within a few hours; meth3d alcohol, 
on the other hand, even in small amounts, is imperfect^ oxidized, and 
the process extends over days instead of hours — a fact which led 
pharmacologists ^ to utter a word of warning concerning the use of 
methyl as a substitute for eth}^l alcohol years before there was a single 
well-kno^vn case of poisoning by it in man, a warning recently justified 
by the hundreds of cases of death and blindness caused by this 
substance.^ 
Having formed the conception that hydrocyanic acid is liberated 
from acetonitrile through the oxidation of the methyl group, I began 
experiments to determine the effects upon the toxicity of the nitrile, 
® The formation of hydrocyanic acid from nitroprussiate of soda, on the other hand, 
is probably the result of a hydrolytic cleavage (Carquet, These, Montpelier, 1903). 
b See Hunt, Johns Hopkins Hospital Bulletin, XIII, p. 213; 1902. 
c See Buller and Wood, Jour. Amer. Med. Assoc., Oct., 1904. 
d An analogy to this supposed mode of decomposition is that of ammonium chloride 
in rabbits. Pohl and Miinzer (Arch. f. exp. Path. u. Pharm., v. 43, p. 28) found that 
when this substance was administered to rabbits the ammonia was converted into urea 
while the hydrochloric acid was liberated and the animals died of acid intoxication; the 
fatal dose of the ammonium chloride corresponded closely to the equivalent amount 
of hydrochloric acid. In a similar manner Kohn and Czapek (Hofmeister’s Beit., v. 8, 
p. 302; 1906) explain the injurious effects of certain salts upon the growth of fungi. 
Some fungi use up the kations and the organisms become poisoned by the acids formed 
from the anions; others use up the anions and become poisoned by the alkalies formed 
from the kations. 
