The toxicity of caffein in the rabbit varies with the mode of its
administration, being least when given by mouth and greatest by
intravenous administration. The toxicity is from 15 to 20 per cent
greater by subcutaneous injections than by mouth, but is about half
of that when injected into the peritoneal cavity. No difference was
observed in the toxicity of caffein whether administered into gluteal
or into the lumbar muscles. When introduced by this route the toxicity
was found to be less by one-third than when it is injected into the
peritoneal cavity, but is about 30 per cent more toxic than the
subcutaneous injections. White or black rabbits were found to be less
resistant to caffein than gray rabbits.
The resistance of the guinea pig to caffein, as of the rabbit,
is greatest when given by mouth. The minimum fatal dose is less
by intraperitoneal injections, but greater than by subcutaneous
injections, thus differing from the rabbit in this regard. The adult
cat is less resistant than the guinea pig or rabbit to caffein. The
minimum lethal dose by mouth is the same as by subcutaneous, and is
less than by intraperitoneal, injection. The minimum fatal dose for
dogs was found to be the same by mouth as by subcutaneous injection and
is almost the same as for the cat. The toxicity of caffein varies in
the guinea pig according to season of the year.
Age is likewise a factor in the toxicity of caffein, young animals
being more resistant than the full-grown and older animals; this was
shown in experiments on rabbits, cats, and dogs. The symptoms of
caffein poisoning also were different in puppies and in full-grown
dogs. Different diets, such as carrots and oats, did not influence
the resistance of rabbits and guinea pigs to caffein. Low protein
diet tends to decrease resistance to caffein in dogs. Young growing
dogs are less resistant to caffein on a meat than on a milk diet.
Caffein is not cumulative in the rabbit or dog, even if administered
for a considerable length of time. Some degree of tolerance may be
induced in the rabbit under certain conditions, but not in dogs under
the conditions of the experiments made in this investigation. The
possibility, however, that dogs may acquire tolerance for caffein
is not excluded. Although the rabbit tolerates a much larger single
dose of caffein than the dog, it was found, in experiments on chronic
intoxication that the rabbit is less resistant to caffein than the
dog. The toxicity of caffein is probably increased under pathological
conditions, since comparatively smaller doses were fatal to rabbits,
cats, and dogs, when marked lesions not due to caffein were found at
autopsy. Glycosuria was observed in rabbits, guinea pigs, and cats when
caffein was given in sufficient amounts.
TABLE 18.--_Acute caffein intoxication: Table showing average
minimum toxic and minimum fatal doses for adult animals._
Table headings:
SC: Subcutaneously.
BM: By mouth.
IP: Intraperitoneally.
IM: Intramuscular.
IV: Intravenous.
-------------+------+-------------------------------------------------
|Effect| Dose per kilo (grams)
Animal. |of +---------+-----------+-----------+-------+-------
|dose. | SC | BM | IP | IM | IV
-------------+------+---------+-----------+-----------+-------+-------
Rabbit, gray |{Toxic| 0.15| 0.325| 0.100| 0.13| 0.05
| | | | -0.125 | -0.15|
|{Fatal| .30| .350| .150| .20| 0.10
| | | | | | -.16
Rabbit, white|{Toxic| | | | |
or black |{Fatal| .20| .290| | |
| | | | | |
Guinea pig |{Toxic|0.15- .16| .150| .200| |
|{Fatal| .20- .24|0.280- .300| .240- .250| |
| | | | | |
Cat |{Toxic| .12- .14| .125| .125- .150| |
|{Fatal| .15| .150| .180- .200| |
| | | | | |
Dog |{Toxic| | .100- .120| | |
|{Fatal| .15- .16| .140- .150| | |
-------------+------+---------+-----------+-----------+-------+-------
NOTE.--The doses given in this table are approximate.