28 
to within 0.01 mgm. per gram body weight. The protocols of the 
experiments described later show what satisfactory results may, 
with careful work, be obtained. 
It has not been possible to determine all the causes of the differ- 
ences in susceptibility of different groups of mice to acetonitrile. 
Diet seems, however, to be the most important single factor; mice 
kept on certain diets for long periods may be many times as resistant 
as others of the same age and weight kept on a different diet. 
Another very important factor in the toxicity is the season. We 
have records of experiments performed in each month for three and 
in some cases for four years. Although the diet was approximately 
the same throughout the year, the mice were invariably more sus- 
ceptible to the acetonitrile during the summer than during the winter 
months. The following table shows the average fatal dose (in milli- 
grams per gram) determined during different months : 
January 
0.56 
May 
0.30 
j September 
.... 0.25 
February 
35 
June 
28 
October 
. . . . .39 
March 
58 
July 
31 
November 
45 
April . 
53 
August 
18 
December 
55 
There were greater variations (in different series of experiments) 
in the winter than in the summer months, but in only three cases 
were the figures as low as the average for the summer months. 
During the winter months the mice were kept in a room heated to 
75° F. (23.9° C.) ; hence it is not probable that the temperature was 
the only factor. a 
On the manner in which thyroid influences the resistance of mice to 
acetonitrile. — We are unable to suggest any entirely satisfactory 
explanation . of how the feeding of thyroid protects mice against 
« D. W. Harrington (Am. J. Physiol., 1898, 1, p. 385) has recorded some very inter- 
esting experiments on the relation of season to the susceptibility of the guinea pig to 
anesthetics and operative procedures; the resistance was very low from February to 
May and highest from October to January. Stimulation of the vagus was more effect- 
ive in stopping the heart during the fall and winter than during the spring months. 
Prof. C. W. Edmunds, of the University of Michigan, found frogs to be much less resist- 
ant to digitalis in April than during the summer months. 
The following statement of F. C. Koch (Proc. Am. Pharm. Ass., 1907, 55, p. 371) 
is very interesting in this connection: “I have recently had occasion to determine 
the per cent of iodine in unadulterated desiccated sheep thyroids prepared at different 
seasons during the last two and one-half years, and found that the desiccations without 
exception test as much as three times higher during the winter months than during 
June and July, and that the per cent gradually diminished toward the summer months 
and then again gradually increased toward the winter.” 
Although it is very probable that the differences found by Koch depend upon 
differences in diet, it is remarkable that the time of the minimum amount of iodine 
in sheep thyroid should coincide with the period of least resistance of mice to acetoni- 
trile; as we shall see later the resistance of animals to acetonitrile is closely dependent 
upon the amount of iodine which their thyroids contain. 
