15 
from experiments with 5 rabbits that the lethal intravenous dose 
is about 0.06 mg. per kilo, although 0.03 mg. per kilo may prove 
very toxic. An intrapleural injection of 2 mg. per kilo or the 
same amount injected intraperitoneall}^ into guinea pigs may prove 
fatal. 
Up to this time toxicity experiments and blood pressure determi- 
nations were primarily (pialitative in nature, yet they furnish a most 
reliable index of the relative purity and activity of adrenal extracts, 
and of the pure products of the active principle thus far made. 
Houghton (38), however, in 1901, emphasized the usefulness of 
quantitative determinations by the blood-pressure method and pub- 
lished records illustrating the relative effect of different volumes 
of the same solution injected subcutaneously. In 1902 (39) he 
proved this method one of the most accurate means of assaying 
adrenalin. Three solutions. A, B, and C, were used, one containing 
85, one 40, and another 130 per cent of adrenalin in a given solution. 
An assistant reported that A contained 80, B 40, and C 135 per cent 
of the amount in the 1-aiovm solution. It was also found that Taka- 
mine’s crystalline product was from 600 to 800 times as active as the 
best aqueous extracts of freshl}^ prepared glands. 
Lawen (46) in 1903 studied the quantitative effect of adrenalin 
upon the blood vessels of frogs. The brain and spinal cord were 
destroyed and, by measuring the outflow from the vessels subjected 
to a given pressure vdth a known solution, he determined the relative 
vaso-constrictor action of the different adrenalin solutions. With a 
pressure equivalent to 30 c. c. of HgO the frogs lasted about two hours. 
Two ten- thousandths of a milligram of suprarenin in a concentration 
of 2:100,000,000 constricted the blood vessels of a 50-gram frog so 
that the outflow was reduced 20 to 37 per cent. In other experi- 
ments it was determined what pressure in excess of the minimum was 
necessary to overcome the increased resistance due to vaso-constric- 
tion. By these experiments Lawen not only could study solutions 
quantitatively, but could even detect the differences between fresh 
solutions and those that had been standing for some time. 
L^p to this time little attention had been given to the possibility 
of using particular organs for assaying adrenalin, but observations 
made by the following writers eventually led to the idea that possibly 
the eye or separate strips of muscle might prove serviceable. 
In 1904 Meltzer and Auer (54), Lewandowsky (50), Boruttau (13), 
and Langley (45) confirmed Foa’s observation that adrenalin extract 
intravenously injected causes dilation of the pupil and that subcuta- 
neous injections have no effect. It is assumed that the extract is 
oxidized in the lymph spaces before it reaches the neuro-muscle 
apparatus and effects dilation. Meltzer (54) states that Ms extensive 
