(28)
achieve the diet
concentrations and batch sizes that were
reportedly used in
the study. A total of 230.0 kg of DKP
was manufacturered
by Searle Chemist Jack Drogt. Following
are tables showing
the quantities of DKP manufactured,
calculalted quantity
required for the study, and quantities
withdrawin from stock.
QUANTITIES MANUFACTURED
Lot #. Quantity (After
Milling)
1R
2R
3R
4R Another FDA gutted
table!
5R
6R
7R
Total
CALCULATED QUANTITIES
REQUIRED FOR THE STUDY
Dose Group Calculated
Quantity Required
Low Dose Males
Mid Dose Males
High Dose Males
Low Dose Females
Another FDA gutted table!
Mid Dose Females
High Dose Females
(29)
QUANTITIES WITHDRAWN
FROM STOCK (FROM COMPOUND INVENTORY CARDS)
Date Withdrawn From
Stock Quantity Lot
10/29/71 kg 1R
1/4/72 kg 1R
2/28/72 kg 4R
3/11/72 kg 3R
3/29/72 kg 2R
9/11/72 kg 3R
10/10/72 kg 2R
* kg 2R
12/1/72 kg 3R
* kg 4R
12/27/72 kg 5R
* kg 2R
1/25/73 kg 5R
3/22/73 kg 6R
4/18/73 kg 5R
7/10/73 )5 kg 6R
8/10/73 )5 kg 6R
9/7/73 kg 6R
11/2/73 kg 7R
Another FDA gutted
table!
TOTAL kg
* These three cards
were not signed or dated.
It should be noted
that only two of the 18 compound inventory
cards
specified that the
SKP withdrawn from stock was to be used
in study
E-77/78 (PT 988S73).
Thirteen of the cards list "Toxicity"
or
"Toxicology"
as the reason for withdrawal. Three of
the cards have
no entries at all,
except for the word "empty".
(Copies of the
compound inventory
cards are attached as Exhibit #28).
The total quantity
withdrawn from stock is kg in excess of
the
amount necessary
to achieve the diet concentrations used
in the study.
(Based on the diet
calculation records attached as Exhibit
#34, which we
used to construct
the diet calculation summary table attached
as Exhibit
#30).
It is not known whether
any of the kg of DKP accounted for on
the 18
compound inventory
cards was withdrawn for use in studies
other than
E-77/78. We could
find no other records to verify the amount
of DKP
withdrawn for, or
used in this study.
(30)
ANIMALS UNDER TEST
Three hundred and
sixty weanling albino rats, CD strain,
180 of each sex,
were used. The rats
were 21 days old when received from the
Copies of shipping
labels were obtained, and
are attached as Exhibit
#10.
The rats were housed
individually in wire cages an were given
a one-week
acclimation period
before being placed on treatment at the
age of four
weeks.
Rockland Rat/Mouse
Diet (complete), , was fed for the first
62 weeks, and /Rat
Chow was used from week 63 until the study
was
terminated at 114
weeks.
The animals were
housed in air conditioned rooms maintained
at 72 degrees
F, with artificial
fluorescent lighting at 12 hours per day
exposure.
The rats were divided
into 12 housing groups, (6 groups per
sex), 30 rats
in each housing group.
Initiation of treatment was staggered
over a 2
week period, beginning
11/8/71.
Each housing group
was composed of dosage groups as follows:
Multiples of No.
of Rats Per
Treatment Dosage
Estimated Daily Housing Group Total
Group gm/kg/day Human
Dosage Male Female Rats
Control
Low
This entire table
was blotted out prior to delivery
Medium
High
RANDOMIZATION OF
ANIMALS
Computer-generated
randomization tables were used for assigning
the dose
and housing groups
(copies of these tables were obtained
and are attached
as Exhibit #6). Each
housing group consisted of 30 animals
(12 controls,
6 low, 6 medium,
and 6 high dose). Each animal was assigned
a letter to
(31)
designate the housing
group (A through M), a cage number (1
through 30),
a letter to indicate
dose group (C,L,M & H), and a letter
to indicate sex
(M or F). For example,
animal A30CM would be a control male,
in housing
group A, occupying
cage number 30 (Exhibit #69).
Each rack (30 animals)
contained a random distribution of control
and
treated animals.
An example of a typical housing group
is shown in the
diagram attached
as Exhibit #7.
The specific problems
of feeding animals housed in the above
manner were
discussed in the
report generated by the task force investigation
of
Aspartame in l975/l976.
We will reiterate them here:
Housing experimental
animals in this manner (controls, low,
medium, & high
dose animals randomly
distributed on the same rack) would greatly
increase
the chance of administering
the wrong diet to the animals. The chance
of
error was compounded
by the method used to feed the animals
which was as
follows: At the specified
intervals, the animals were weighed, and
the
empty food jars were
removed, weighed and new food jars placed
in the
cages. The new (filled)
food jars were placed on a mobile cart
in rows
corresponding to
dose group (See Exhibit #8). The cart
was wheeled to the
Intec Unit and placed
up against it with the rows of high dose
jars
farthest away from
the operator. The operator started from
the upper left
corner of the housing
rack, (See Exhibit #7), removed the mylar
card from
the cage and inserted
it into the Intec Unit. This printed out
the
animal's identification
number. A color coded card for dose level,
also
bearing the animal
number, remained on the cage. The technician
then
opened the cage,
removed the animal, placed it on the scale
pan, pushed
the button to register
the weight and returned the animal to
its cage. He
then removed the
empty food jar, placed it on the scale
and pushed the
button to record
the empty feeder weight. The empty jar
was placed on
another mobile cart
provided for that purpose. The new (filled)
jar was
selected from the
appropriate row according to dose level
(Exhibit #8),
placed on the scale,
weight recorded, and the jaw placed in
the cage. The
Card was then removed
from the Unit and replaced on the cage.
