**Although the date found dead was listed as 1/9/74 on the gross pathology sheet, the "Tissue Masses & Deaths" book listed this date as 7/25/73.

The gross pathology sheet for one of the above animals, F6HF, described a tissue mass measuring 5.0 X 4.5X2.5 cm.  This tissue mass was first observed on 8/24/73 according to the pathology sheet (Exhibit #79), the observation records (Exhibit #70), and the palpation record in the "Tissue Masses and Deaths" book (Exhibit #65).  The submission to FDA (Exhibit #8) reported no tissue mass and the animal was excluded from the study due to marked autolysis.

In addition to the above twenty animals that were excluded from the study, many other animals exhibited marked autolysis.  For example, D27LF, M25CF, and H12CF are all described grossly in the submission to FDA as follows; "all organs examined grossly were markedly autolyzed".

Records for approximately 30 animals showed substantial differences between gross observations on pathology sheets, when compared with the individual pathology summaries submitted to FDA.  Following is a detailed comparison of ten of these.  (Copies of all the gross pathology sheets, and the pathology summaries submitted to FDA are attached as Exhibits #78, #79, and #86).

A2CM

Submission to FDA:

Lung         - Focal adhesion

Adrenal      - Moderately enlarged

All other organs examined grossly were unremarkable.

Original Pathology Sheet:

Pituitary - Missing

Lung      - Left, mid-portion adheres to the medial area of the rib cage by a "fibrous" type of tissue.  (Submitted together with relevant portion of the rib cage).

Right, post-caval lobe has undergone consolidation.  Contains grayish-yellowish nodules measuring 2 x 2 mm.  (Entire lung submitted in toto)

Lymph Nodes, Pancreatic - Slightly enlarged

Adrenal   - Left, moderately enlarged.  Right and left, covered with tiny yellow spots measuring 1.0 x 1.0 mm.

Lymph Nodes, Mesenteric - moderately enlarged.

Mass - previously described on 8/20/73 has since then regressed.

Prostate - Marked atrophy, all lobes

Seminal Vesicles - Marked atrophy, bilaterally

All other organs examined were grossly normal and unremarkable.

M15CF

Submission:

Mammary gland   - subcutaneous mass located in mid-thoracic region measuring 7 x 6 x 2.5 cm.

Urinary bladder - papillary growth in the lumen.

All other organs examined grossly were unremarkable.

Original:

Mass #1 - Previously described in the left inguinal region on 2/9/73 has since then regressed.

Masses #2 and # - Located in the mid-axillary-cervical regions are all on mass now measuring 7.0 x 6.0 x 2.5 cm and may be described as irregular in shape, multi-nodular, smooth-surfaced, non-glistening, No Spinal Cord    yellowish-purpulish in color, non-adherent to the VL           underlying muscle and containing a whitish-yellowish firm tissue within.  (Submitted in toto together with  remainder of tissue).

 Heart             - Left Ventricle - dilitation and walls thin.

 Spleen            - Slightly enlarged

 Liver             - Prominent lobular architecture.

 Adrenal           - Left, slightly enlarged.  Right, unremarkable.

 Ovary             - Right, small cyst measuring 4.0 x 4.0 mm and distended with a clear yellow fluid.

All other organs examined were grossly normal and unremarkable.

G10LM

Submission:

Testis  - Marked atrophy, unilaterally.

Kidney  - Moderate enlargement, mottled appearance, bilaterally.

Small and large intestine exhibited moderate autolysis, no sections submitted.

All other organs examined were grossly normal and unremarkable.

Original:

Mass which was initially palpated on 2/9/72 (86 days Rx) in the left inguinal area was actually the left testis which ascended and went thru weakened left inguinal ring into the subcutaneous area.

Testis  - Left (ascended) appears atrophied (submitted in toto).

Kidney  - Moderate, diffuse and uniform enlargement, mottled, bilaterally (submitted in toto).

 Small and large intestines are moderately autolyzed (no sections submitted).

 Thyroid   - Moderately enlarged, bilaterally.  A 2 mm in dia., discrete, sl raised, moderately firm yellowish-grey lesion is located in the posterior tip, bilaterally. (Thyroid submitted in toto wrapped in a lens paper).

All other organs examined were grossly normal and unremarkable.

 L11LM

Submission:

Kidney     - Mottled appearance

Testes     - Marked atrophy, bilaterally

Prostate   - Marked atrophy

All other organs examined grossly exhibited marked autolysis.

Original:

Adrenal    - Pale yellow, bilaterally

Kidney     - Pale yellow, bilaterally, rough-surfaced, bilaterally, moderately autolyzed, bilaterally, tiny spaces in the cortex region measuring about 1 mm in diameter, bilaterally.

Testes     - Marked atrophy, bilaterally, marked autolysis, bilaterally.

Prostate   - Marked atrophy, all lobes

Seminal Vesicles - Marked atrophy, bilaterally

Spleen     - Marked autolysis

Pancreas   - Marked autolysis

Stomach    - Marked autolysis.  A glandular portion - numerous, tiny,  pitted ulcerations measuring 1 -4 mm in diameter.

Lymph Nodes, Mesenteric - Marked autolysis

Heart      - Wall of left ventricle thin

Brain      - Marked autolysis

Pituitary  - Marked autolysis

Liver      - Marked autolysis

All other organs examined were grossly normal and unremarkable.

M17LF

Submission:

Pituitary        - Marked enlargement.

Adrenal          - Markedly enlarged and hyperemic, bilaterally.

Mammary Gland    - Mass 1, located subcutaneously in left axillary region, measuring 3 X 3 X 2.5 cm; mass 2, located subcutaneously adjacent to mass 1, measuring 3 X 2 X 1 cm; mass 3, located subcutaneously in the right axillary region, measuring 2.5 X 2 X 1 cm; mass 4, located subcutaneously in the left inguinal region, measuring 3 X 1 X 1 cm; mass 5, located subcutaneously in the right inguinal region, measuring 2 X 1.5 X 1 cm.

All other organs examined grossly were unremarkable.

Original

Pit         - appears markedly hyperemic

Adrenal     - Exhibits numerous minute greyish spots on the serosal surface bilaterally.  It appears markedly enlarged.

Mass (1)    - A 3 X 3 X 2.5 cm. spheroidal, multinodular, yellowish white, slightly firm mass located subcutaneously in the left axillary area.  Mass non-adherent to the surrounding muscles or tissue (submitted in toto).

Mass (2)    - A 2.5 X 2 X 1 cm spheroidal, smooth, yellowish white firm mass located subcutaneously and adjacent to the above described mass (submitted in toto) mass non-adherent to the surrounding muscles or tissues.

Mass (3)    - A 2.3 X 2 X 1 cm. irregularly shaped, multinodular, yellowish white, firm mass located subcutaneously on the rt. axillary area.  Mass non-adherent to the surrounding muscles or tissues (submitted in toto).

Mass (4)    - A 3 X 1 X 1 cm. elongated, multinodular, yellowish white, firm mass located subcutaneously on the left inguinal area.  Mass non-adherent to the surrounding muscles or tissues (submitted in toto).

Mass (5)    - A 2 X 1.5 X 1 cm. flat, multinodular, yellowish white, firm mass located subcutaneously on the rt. inguinal area.  Mass non-adherent to the surrounding muscles or tissues (submitted in toto).

All other organs examined were grossly normal and unremarkable.

C1MM

Submission

Kidney        Marked enlargement with yellowish discoloration.

Testis        Marked atrophy, bilaterally.

Tissue mass located subcutaneously in the right inguinal area measuring 2.5 X 1 cm.

All other organs examined grossly were unremarkable.

Original:

Mass       - Previously described on 12/9/72 and located subcutaneously in the right inguinal area now measures 2.5 X 2.0 X 1.0 cm and may be described as smooth-surfaced, purplish- yellowish in color, non-glistening, firm, multi-nodular, non-adherent to the underlying muscles and containing a firm yellowish-whitish tissue.  (Submitted in toto together with a portion of the skin and underlying muscle with remainder of tissue).

Heart      - Left ventricle has undergone a moderate amount of dilitation.  Wall, left ventricle is thin.

Liver      - Prominent lobular architecture.

Lung       - Right, post-caval lobe-consolidation.

Kidney     - Markedly enlarged, yellow and rough-surfaced, bilaterally. Dilitation of the pelvis.

Adrenal    - Covered with tiny yellow spots measuring 1 mm in diameter,  bilaterally.

Testes     - Marked atrophy, bilaterally.

All other organs examined were grossly normal and unremarkable.

Tiss. Trimming -  Nodules discovered immediately posterior (2.0 cm) to the pyloric portion of the stomach within the adipose tissue.  Nodules may be described as firm, yellowish brownish in color.  Non-glistening measuring 1.2 X 1.0 mm to 4.0 X 4.0 mm.

E27MM

Submission:

Lung         - Moderate diffuse hyperemia.

Eye          - Opaque cornea, bilaterally.

All other organs examined grossly were unremarkable

Original:

Lungs - All lobes exhibit moderate diffuse and uniform hyperemia.

Kidney      - Moderate autolysis.

Eye         - The entire cornea is opaque, bilaterally.

Spleen      - Moderately autolyzed.

Stomach     - Numerous 1-2 mm. hemorrhagic ulcerations are located on the glandular mucosa.  Entire small and large intestines are moderately autolyzed.

Brain & Pituitary - Moderately autolyzed.

All other organs examined were grossly normal and unremarkable.

A1HM

Submission:

All organs examined were grossly unremarkable.

Original:

Testes       - Markedly atrophy, bilaterally

Lung, Rt     - Middle lobe exhibits a 1 X 1 cm consolidation on the posterior portion.

Liver        - All lobes appear olive green otherwise unremarkable.

All other organs examined were grossly normal and unremarkable.

L27HM:

Submission:

Testes      - Right, slightly enlarged; left, mild atrophy.

All other organs examined grossly were unremarkable.

Original:

Testes      - lt./appears markedly atrophy rt./appears to be distended with yellowish white substance

Seminal V-  Appears markedly atrophy bilaterally.

Intestinal  - Large, markedly distended with "gas".

All other organs examined were grossly normal and unremarkable.

P.M. Testes - Also, small black areas are noted within along with the yellowish areas.  Black areas measuring 1.0 X 1.0 to 4.0 X 4.0 mm in diameter.

J30HM

Submission:

Lung    - Moderate consolidation of all right lobes.

Testis  - Moderate atrophy

All other organs examined grossly were unremarkable.

Original:

Pituitary  - Markedly enlarged; slightly hyperemic.

Heart      - Left Ventricle has undergone dilitation walls thin.

Lung       - Right, anterior, medial and post-caval lobe have undergone consolidation.

Testes     - Marked atrophy, bilaterally.

Seminal Vesicle - Marked atrophy, bilaterally.

All other organs examined were grossly normal and unremarkable.