J. D. E. Holmes 
79 
Ehrlich (1908) assumes that “ the arsanilate as such exercises no 
action at all in the organism, but that only the very small portion 
which undergoes a reduction in the living organism is the actual 
lethal agent.” 
Some authors still believe that arsenic is split off in the body and 
that no action of atoxyl is due to this free arsenic. 
Breinl and Nierenstein (1909) repeated the experiments of Levaditi 
and Yamanouchi, but only occasionally got positive results, and in these 
cases free arsenic was demonstrated in the solution of atoxyl. They 
conclude that “the assumption that a complicated reduction, product of 
atoxyl, is formed, is superfluous.” According to their view the atoxyl 
action may be regarded as the result of a simple oxidation, by means of 
which arsenic is set free from the benzene ring. The finding of free 
arsenic in the urine, they say also, supports this view. 
Tendron (1909), Wedemann (1908), Nierenstein (1908-09) and 
others found arsenic in the urine after the administration of atoxyl. 
Uhlenhuth and Woithe (1908) are of opinion that the action of 
atoxyl is clearly not direct, but they repeated Levaditi and Yamanouchi’s 
trypanotoxyl experiments with negative results. They do not agree 
with Ehrlich on his reduction theory. They think that the atoxyl 
stimulates the cells to a heightened production of substances which 
injure the parasites and that there is no direct action of reduced atoxyl. 
All our observations on the action of atoxyl are in support of the 
view that a small amount of cleavage occurs and that the therapeutic 
effect is entirely due to the presence of free arsenic. We were unable 
to get any positive trypanotoxyl results in repeated experiments. 
Atoxyl is a very convenient method of administering arsenic hypo¬ 
dermically or intravenously, but, even in this form, it is impossible 
to give arsenic without toxic effect in quantities sufficient to per¬ 
manently sterilise the tissues. 
Both the toxic and therapeutic effects of arsenic and atoxyl adminis¬ 
tered intravenously and subcutaneously are much alike. Arsenic given 
hypodermically from 0'25 to 0'5 grammes, while it produces sloughing, 
frees the blood from trypanosomes at the same time and keeps the 
circulation free from the parasites for about the same period as 2 grammes 
of atoxyl injected subcutaneously. 
When lethal doses are given subcutaneously or intravenously the 
symptoms of poisoning are produced about the third day. With atoxyl 
the kidneys are the seat of the chief macroscopical lesions, death, as a 
rule, being due to acute nephritis. 
