of the four groups received a
daily intravenous dose of Borazidine, delivered at a concentration of
either 100, 250, 500, or 10,000 mg/kg/day.
Within the high-dose
group (10,000 mg/kg/day) effects were immediate and catastrophic,
resulting in death within 20 mins of dosing for all but one of the
five animals. Animals 93445 and 93557, pre-death, exhibited vomiting
and disorientation. These two animals almost immediately entered a
catatonic state and were sacrificed moribund. Animals 93001 and 93458
exhibited vomiting, anxiety, disorientation, and digging at their
abdomens. These animals also quickly entered a catatonic state and
were sacrificed moribund.
Only one animal within
this high-dose group, animal 93990, a diminutive 26 kg male, appeared
unaffected.
All of the animals that
had succumbed were removed from the enclosure and necropsied. Cause
of death was seen, in all cases, to be renal failure.
No effects were seen on
Day 1 in any of the three lower-dose groups (i.e., 100, 250, or 500
mg/kg/day).
On Day 2, after the
second round of dosing, animals in the 500 mg/kg/day group began to
exhibit vomiting, and, in some cases, aggressive behavior. This
aggressive behavior most often consisted of a directed shrieking,
with or without feigned biting. Some animals in the two lowest-dose
groups (100 and 250 mg/kg/day) were observed to vomit, and one in the
250 mg/kg/day group (animal 93002) appeared to exhibit
self-scratching behaviors similar to those seen earlier in the
high-dose group (i.e., probing and scratching at abdomen, with
limited writhing).
By the end of Day 3,
three of five animals in the 500 mg/kg/day group had entered a
catatonic state and the other two animals in this dose group were
exhibiting extreme writhing punctuated with attempted biting and
pinching of their fellows, often with shrieking. Some hair loss,
ranging from slight to extreme, was observed, as was some "playing"
with the resulting hair bundles. This "playing" behavior
ranged from mild to quite energetic. This "playing"
behavior was adjudged to be typical of the type of "play"
such an animal might initiate with a smaller animal such as a rodent,
i.e., out of a curiosity impulse, i.e., may have been indicative of
hallucinogenic effects. Several animals were observed to repeatedly
grimace at the hair bundles, as if trying to elicit a fear behavior
from the hair bundles. Animal 93110 of the 500 mg/kg/day group was
observed to sit in one corner of the cage gazing at its own vomit
while an unaffected animal (93222) appeared to attempt to rouse the
interest of 93110 via backpatting, followed by vigorous backpatting.
Interestingly, the sole remaining high-dose animal (93990, the
diminutive male), even after the second day's dosage, still showed no
symptoms. Even though this animal was the smallest in weight within
the highest-dose group, it showed no symptoms. It showed no vomiting,
disinterest, self-scratching, anxiety, or aggression. Also no hair
loss was observed. Although no hair bundles were present (because no
hair loss occurred), this animal was not seen to "play"
with inanimate objects present in the enclosure, such as its food
bowl or stool or bits of rope, etc. This animal, rather, was seen
only to stare fixedly at the handlers through the bars of the cage
and/or to retreat rapidly when the handlers entered the enclosure
with the long poking sticks to check under certain items (chairs,
recreational tire) for hair bundles and or deposits of runny stool.
By the middle of Day 3,
all of the animals in the 500 mg/kg/day group had succumbed.
Pre-death, these showed, in addition to the effects noted above,
symptoms ranging from whimpering to performing a rolling
dementia-type motion on the cage floor, sometimes accompanied by
shrieking or frothing. After succumbing, all five animals were
removed from the enclosure and necropsied. Renal failure was seen to
be the cause of death in all cases. Interestingly, these animals
daily intravenous dose of Borazidine, delivered at a concentration of
either 100, 250, 500, or 10,000 mg/kg/day.
Within the high-dose
group (10,000 mg/kg/day) effects were immediate and catastrophic,
resulting in death within 20 mins of dosing for all but one of the
five animals. Animals 93445 and 93557, pre-death, exhibited vomiting
and disorientation. These two animals almost immediately entered a
catatonic state and were sacrificed moribund. Animals 93001 and 93458
exhibited vomiting, anxiety, disorientation, and digging at their
abdomens. These animals also quickly entered a catatonic state and
were sacrificed moribund.
Only one animal within
this high-dose group, animal 93990, a diminutive 26 kg male, appeared
unaffected.
All of the animals that
had succumbed were removed from the enclosure and necropsied. Cause
of death was seen, in all cases, to be renal failure.
No effects were seen on
Day 1 in any of the three lower-dose groups (i.e., 100, 250, or 500
mg/kg/day).
On Day 2, after the
second round of dosing, animals in the 500 mg/kg/day group began to
exhibit vomiting, and, in some cases, aggressive behavior. This
aggressive behavior most often consisted of a directed shrieking,
with or without feigned biting. Some animals in the two lowest-dose
groups (100 and 250 mg/kg/day) were observed to vomit, and one in the
250 mg/kg/day group (animal 93002) appeared to exhibit
self-scratching behaviors similar to those seen earlier in the
high-dose group (i.e., probing and scratching at abdomen, with
limited writhing).
By the end of Day 3,
three of five animals in the 500 mg/kg/day group had entered a
catatonic state and the other two animals in this dose group were
exhibiting extreme writhing punctuated with attempted biting and
pinching of their fellows, often with shrieking. Some hair loss,
ranging from slight to extreme, was observed, as was some "playing"
with the resulting hair bundles. This "playing" behavior
ranged from mild to quite energetic. This "playing"
behavior was adjudged to be typical of the type of "play"
such an animal might initiate with a smaller animal such as a rodent,
i.e., out of a curiosity impulse, i.e., may have been indicative of
hallucinogenic effects. Several animals were observed to repeatedly
grimace at the hair bundles, as if trying to elicit a fear behavior
from the hair bundles. Animal 93110 of the 500 mg/kg/day group was
observed to sit in one corner of the cage gazing at its own vomit
while an unaffected animal (93222) appeared to attempt to rouse the
interest of 93110 via backpatting, followed by vigorous backpatting.
Interestingly, the sole remaining high-dose animal (93990, the
diminutive male), even after the second day's dosage, still showed no
symptoms. Even though this animal was the smallest in weight within
the highest-dose group, it showed no symptoms. It showed no vomiting,
disinterest, self-scratching, anxiety, or aggression. Also no hair
loss was observed. Although no hair bundles were present (because no
hair loss occurred), this animal was not seen to "play"
with inanimate objects present in the enclosure, such as its food
bowl or stool or bits of rope, etc. This animal, rather, was seen
only to stare fixedly at the handlers through the bars of the cage
and/or to retreat rapidly when the handlers entered the enclosure
with the long poking sticks to check under certain items (chairs,
recreational tire) for hair bundles and or deposits of runny stool.
By the middle of Day 3,
all of the animals in the 500 mg/kg/day group had succumbed.
Pre-death, these showed, in addition to the effects noted above,
symptoms ranging from whimpering to performing a rolling
dementia-type motion on the cage floor, sometimes accompanied by
shrieking or frothing. After succumbing, all five animals were
removed from the enclosure and necropsied. Renal failure was seen to
be the cause of death in all cases. Interestingly, these animals
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