FDA report on Searle's submission for NutraSweet approval 1977 - Part 15

Back to Aspartame Articles

Part: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23




Bart Tangonan

Tony Martinez

David Kie

Robert Spaet


The above four persons in the toxicology department were involved with

assembling data for clinical chemistry and hematology determinations for

April 1973 to Feb. l974.


Joyce Schulmann - performed urinalysis and hematology determinations from

April l973 to Feb. l974.


Philip Muellner - Technician in Path-Tox Dept. July l970 till end of



Janet Praal - Technician, prepared individual work sheets for urinalysis.

No longer employed by Searle.


C. The following employees were interviewed regarding clinical lab

procedures, and methods for recording clinical lab. data.


1) Bart Tangonan on 6/1/77 regarding the recording of data.


2) Judith Beauchamp, on 6/2/77 regarding hematology and urinalysis.


3) Judith Schmal, on 6/2/77, 6/7/77, and 7/29/77 regarding clinical



4) Tony Martinez, on 6/3/77 regarding urine and blood collection,

and recording of data.


5) Jane Drury, on 6/7/77 regarding electrophoresis.


Accounts of these interviews are attached as exhibits #47-54.


D. Other Documents and Procedures Used to Authenticate Clinical

Laboratory Data values in Submission were as follows:


1) One loose leaf volume entitled "SC-19192: 104 Week Oral

Toxicity Study In The Rat. PT - 988573 Protocols, Organ

Weights, Dosage, Hematology, Urinalysis, Blood Chemistry,

Protein Electrophoresis." The volume was subdivided into

sections according to the above parameters. The individual




pages (See Exhibit #77, Section IX for example) are composed

of forms containing the appropriate measurements and units

printed on the left side of the page onto which data on

"sticky back sheets" corresponding to each of these

measurements were pasted in columns representing the various

time periods. These pages, in addition to other information,

were headed by the identifying number of the rat for which

the measurements were made. The information on the sticky

back sheets (see Exhibit #77, Sec. IX) was copied (hand

written) from laboratory notebooks, sheets, Auto-

analyzer Charts, teletype sheets (on line data generated by

analytical instruments) or computer printouts (containing

raw and calculated data resulting from on line or off line

input data from instruments) by individuals of General

Toxicology Section (see interview with Bart Tangonan).

Many of the pages were initialed "BRT" (apparently by Bart

R. Tangonan). Most of the final values transcribed into

the sticky back sheets resulted apparently from calculations

made directly by the analytical instruments or by external

computer using the appropriate stored equations and data for

the reference standards.


(2) Since the values appearing in the volume referred to in the

above section were copied from other sources, an attempt was

made to verify these values by examining the information in

these sources. No attempt was made to recover the teletype

sheets, or computer printouts which we were told were no

longer available or could not be recovered (see interview

with Judith R. Schmal, Exhibit #54). All laboratory notebooks

that might contain the original data were requested. Notebooks

dated prior to the dates of the DKP study were excluded. The

appropriate laboratory notebooks were then identified by BA

numbers which were listed on the top sections of the sticky

back sheets included in the volume referred to above.

Examination of these few laboratory notebooks revealed only a

very small amount of data would could be used for additional

verification of the values in the submission. It was necessary

to obtain the consultation of Judith Schmal to clarify the

system used to relate the values in these books with the

corresponding rat and period of time of bleeding. The following

notebooks, as designated by information on the front covers,

were examined:




1) Lab. notebook #N-26375 (hematology), 25 June 71 to 1/21/72.


2) Lab notebook #127133 (phenylalanine), 10/8/71 to 4/21/72.


3) *Lab notebook #113239 (cholesterol), dated 5/1/72.


4) *Lab notebook #17, BA #0007118926 (SGOT), 12/27/71 to 2/25/72.


5) Lab notebook #126472 (phenylalanine), 4/21/72 to 6/8/72.


6) Blue Book #1591, identified "JF VON - 70" (hematology).


7) Columnar book #21, identified "JF VON 27" (Differential cell



8) Spiral notebook identified "JABEA-" (coagulation/prothrombin)

dated 7/23/71.


9) *Spiral notebook #16, (SGOT), 8/27/71 to 12/16/71.


*Those books (3,4, & 9 above) marked with an asterisk provided us with no

useable data, because a formula or standard curve (no longer available)

was necessary to convert the data.


Copies of the applicable pages from all of the above notebooks were

obtained, and are included in exhibit #77.


The following data were cross checked against available data from original

entries (in addition to being checked against transcribed data on "sticky

back sheets" in bound volume):


1. Hematology - Erythrocytes:

Treatment days 42,91,364 & 546 Males and Females.


2. Hematology - Leucocytes, WBC:

Treatment Days 42, 91, 364, & 546 Males and Females.


3. Hematology - Leucocytes, Differential:

Treatment Days 42,91,189,364, & 546, Males and Females.


4. Hematology - Coagulogram, Prothrombin Time:

Treatment Days 42 & 91, Males and Females.




5. Phenylalanine.

Treatment Days 42,189 Males and Females, Day 91 Males.


E. Discrepancies were found between the clinical laboratory

methods described on pages 5-7 of submission Volume 1

(referenced on page 120) and those actually carried out.

These discrepancies were documented by the interviews

described in Section C and in a document (Exhibit #77,

Section II) voluntarily submitted by Jutidy Schmal, June

7, 1977 in response to requests for clarification of the

clinical chemistry procedures as they were actually conducted

in regard to analytical methology instrumentation, and

processing and recording of data.


1) Glutamic Pyruvic Transaminase.


Reference: Russell, C.D. and Cotlove, E. (1971)/

Clin. Chem. 17; 1114


The reference describes a coupled reaction U.V. assay for

serum glutamic oxaloacetic transaminase in which malic

dehydrogenase is used.


As described by Judith R. Schmal (June 7,1977) glutamic

pyruvic transaminase was assayed by a method adopted from

Sigma Kit Technical bulletin #410 - U. V. using Lactic acid



2) Glutamic Oxaloacetic Transaminase


Reference: Same as in (1) above.


As described by Judith R. Schmal (June 7, 1977), from Novem-

ber 1971 to March 15, 1972 a manual colorimetric method

(Fermco Kit) was used (employing dinitrophenylhydrazine).

From March 15, 1972 the method used was adapted from Sigma

Kit, Technical bulletin #410 - U. V. using Lactic acid



3) Blood (serum) urea nitrogen.


Reference: Marsh, (Marsh in Submission) W.H., Fingerhut,

B. and Miller, H. (1965). Clin Chem 11, 624.


The referenced method calls for reaction of urea with diacetyl

monoxime in the presence of thiosemicarbazide and ferric

ions in a relatively weak acid solution.


Continue to Part 16


NEW! Splenda® Exposed
Detox Program eBook Thumbnail

Read about SweetPoison
Buy SweetPoison

Dr. Janet Starr Hull's Newsletter:


Aspartame Dangers Revealed | Disclaimer | Link to us | Contact read tab | Site Map | Search
© Copyright 2002. SweetPoison.com All rights reserved