blending

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CALCULATING DIET CONCENTRATION & BLENDING OF TREATMENT MIXTURES

There were no batch records to show the quantities of DKP and basal diet weighed, type of mixer used, mixing time, dates, or names of individuals performing the weighing and blending operations. We were told that mixing was performed in a Hobard mixer, and that mixing times were about 10 minutes. There was no evidence that any tests had been done to determine theblending charactoeristics of the mixer, or to validate the 10 minute mix time. Fresh batches were mixed on a weekly, bi-weekly, or monthly basis, and batch size ranged from 6 kilograms to 28 kilograms during the study.

The concentration of DKP in the basal diet was calculated by the Mat-Stat Department on a weeklly, bi-weekly, or monthly basis (based on the food consumtion for the previous time period), and submitted to the Path-Tox Department as a Food Concentration Prediction record. The concentration was expressed as grams of DKP per kilogram of basal diet. The Path-Tox Department PErsonnel thenmultiplied the grams of compound indicated on the prediction record by the number of kilograms of diet mix needed to arrive at the proper quantities of DKP and basal diet to be blended. THe concentrations were calculated to yield the proper dosage levels of 9.75, 1.5, and 3.0 grams of DKP per kilograms of body weight per day, for the low, medium, and high dose groups. (Copies of Diet Calculation Records are attached as Exhibit #34). At the end of each treatment period, the remaining treatment mistures were discaded and fresh batches were made.

Now reserve sample of either the DKP or the DKP/diet mixtuures used in this study were retained according to Searle.

DKP was withdrawin from stock by means of a compound inventory card, which was filled out by the person requesting the material. Tony Martinez was the person that usually requested DKP for use in study E-77/78. We examined eighteen (18) compound inventory cards which accounted for 177.0 kg of DKP withdrawon from stock. According to our calculations a total of 152.81 kg of DKP would have been necessary 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	DATA REMOVED BY FDA CENSORS
2R	DATA REMOVED BY FDA CENSORS
3R	DATA REMOVED BY FDA CENSORS
4R	DATA REMOVED BY FDA CENSORS
5R	DATA REMOVED BY FDA CENSORS
6R	DATA REMOVED BY FDA CENSORS
7R	DATA REMOVED BY FDA CENSORS
8R	DATA REMOVED BY FDA CENSORS

TOTAL - DATA REMOVED BY FDA CENSORS

CALCULATED QUANTITIES REQUIRED FOR THE STUDY

Dose Group	Calculated Quantity Required
Low Dose Males	DATA REMOVED BY FDA CENSORS
Mid Dose Males	DATA REMOVED BY FDA CENSORS
High Dose Males	DATA REMOVED BY FDA CENSORS
Low Dose Females	DATA REMOVED BY FDA CENSORS
Mid Dose Females	DATA REMOVED BY FDA CENSORS
High Dose Females	DATA REMOVED BY FDA CENSORS

QUANTITIES WITHDRAWN FROM STOCK (FROM COMPOUND INVENTORY CARDS)

Date Withdrawn From Stock	Quantity	Lot
10/29/71	(DATA REMOVED) KG	1R
1/4/72	(DATA REMOVED) KG	1R
2/28/72	(DATA REMOVED) KG	4R
3/11/72	(DATA REMOVED) KG	3R
3/29/72	(DATA REMOVED) KG	2R
9/11/72	(DATA REMOVED) KG	3R
10/10/72	(DATA REMOVED) KG	2R
*	(DATA REMOVED) KG	2R
12/1/72	(DATA REMOVED) KG	3R
*	(DATA REMOVED) KG	4R
12/27/72	(DATA REMOVED) KG	5R
*	(DATA REMOVED) KG	2R
1/25/73	(DATA REMOVED) KG	5R
3/22/73	(DATA REMOVED) KG	6R
4/18/73	(DATA REMOVED) KG	5R
7/10/73	(DATA REMOVED) KG	6R
8/10/73	(DATA REMOVED) KG	6R
9/7/73	(DATA REMOVED) KG	6R
11/2/73	(DATA REMOVED) KG	7R

TOTAL (DATA REMOVED) 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 (DATA REMOVED) 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 (DATA REMOVED) 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.