TDMS Study 99033-03 Pathology Tables
NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 FINAL #3 TG:P16 MICE Facility: BIORELIANCE Chemical CAS #: 22839-47-0 Lock Date: 07/20/01 Cage Range: All Reasons For Removal: All Removal Date Range: All Treatment Groups: Include All Page 1 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 1| 7| 7| 7| 1| 7| 7| 7| | | | 5| 6| 5| 6| 5| 5| 5| 3| 6| 6| 6| 9| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 8| 8| 8| 8| 8| 8| 8| 8| 8| 9| 9| 9| 9| 9| 9| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Esophagus | + + M + + + + A + + M + + + + | 12 | |__________________________________________________________________________|____________| Gallbladder | + M + + + + + A + + + A + + + | 12 | |__________________________________________________________________________|____________| Intestine Large, Colon | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Rectum | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Intestine Large, Cecum | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Intestine Small, Duodenum | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Intestine Small, Jejunum | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Intestine Small, Ileum | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Lymphocyte | 2 | 1 2.0| Inflammation, Chronic Active | 1 | 1 1.0| |__________________________________________________________________________|____________| Pancreas | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Salivary Glands | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 1 1 1 | 4 1.0| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + A + + + | 14 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Tongue | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 2 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 1| 7| 7| 7| 1| 7| 7| 7| | | | 5| 6| 5| 6| 5| 5| 5| 3| 6| 6| 6| 9| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 8| 8| 8| 8| 8| 8| 8| 8| 8| 9| 9| 9| 9| 9| 9| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| CARDIOVASCULAR SYSTEM - cont | | | |__________________________________________________________________________|____________| Blood Vessel | + + + M + + + M + M + + + + + | 12 | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 1 2 1 1 1 1 1 1 1 1 1 1 2 | 14 1.1| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Islets, Pancreatic | + + + + + + + A + + + + + + + | 14 | |__________________________________________________________________________|____________| Parathyroid Gland | M + M + M + + M + M M M + M + | 7 | |__________________________________________________________________________|____________| Pituitary Gland | I + + + I + I M M + + + + + + | 10 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | Ultimobranchial Cyst | X | 1 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Clitoral Gland | M M M M + + M M + + + M + + + | 8 | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Uterus | + + + + + + + + + + + + + + + | 15 | Endometrium, Hyperplasia, Cystic | 2 2 2 2 2 1 2 1 2 2 1 2 3 2 | 14 1.9| |__________________________________________________________________________|____________| Vagina | + + M + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 3 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 1| 7| 7| 7| 1| 7| 7| 7| | | | 5| 6| 5| 6| 5| 5| 5| 3| 6| 6| 6| 9| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 8| 8| 8| 8| 8| 8| 8| 8| 8| 9| 9| 9| 9| 9| 9| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Bone Marrow | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + A + + + + + + + | 14 | Inflammation, Chronic Active | 3 | 1 3.0| |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + A + + + + + + + | 14 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + + + A + + + + + + + | 14 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 1 4 2 2 2 | 5 2.2| Pigmentation | 1 | 1 1.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + A + + + + + + + | 14 | Atrophy, Diffuse | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + A + + + A + + + | 13 | |__________________________________________________________________________|____________| Skin | + + + + + + + A + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | |__________________________________________________________________________|____________| Bone | + + + + + + + + + + + + + + + | 15 | Cranium, Osteoporosis | 1 | 1 1.0| |__________________________________________________________________________|____________| Skeletal Muscle | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | Granuloma | 2 | 1 2.0| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 4 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 1| 7| 7| 7| 1| 7| 7| 7| | | | 5| 6| 5| 6| 5| 5| 5| 3| 6| 6| 6| 9| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 8| 8| 8| 8| 8| 8| 8| 8| 8| 9| 9| 9| 9| 9| 9| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| NERVOUS SYSTEM - cont | | | Cerebellum, Medulla, Vacuolization | | | Cytoplasmic | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Larynx | + M + M M + I M M I M + M M I | 4 | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | Alveolar Epithelium, Hyperplasia, | | | Focal | 1 | 1 1.0| Alveolus, Crystals | 4 | 1 4.0| |__________________________________________________________________________|____________| Nose | + + + + + + + + + + + + + + + | 15 | Olfactory Epithelium, Hyaline Droplet| 2 2 | 2 2.0| Respiratory Epithelium, Hyaline | | | Droplet | 2 | 1 2.0| |__________________________________________________________________________|____________| Trachea | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | |__________________________________________________________________________|____________| Eye | + + + + + + + + + + + A + + + | 14 | Cataract | X | 1 | |__________________________________________________________________________|____________| Harderian Gland | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Zymbal's Gland | + M M + M M + + + + + + + + M | 10 | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | Nephropathy | 1 | 1 1.0| Renal Tubule, Dilatation, Diffuse | 2 | 1 2.0| Renal Tubule, Dilatation, Focal | 1 1 1 1 1 1 1 1 1 1 | 10 1.0| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 5 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 1| 7| 7| 7| 1| 7| 7| 7| | | | 5| 6| 5| 6| 5| 5| 5| 3| 6| 6| 6| 9| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 8| 8| 8| 8| 8| 8| 8| 8| 8| 9| 9| 9| 9| 9| 9| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM - cont | | | |__________________________________________________________________________|____________| Urinary Bladder | + + + + + + + A + + + + + + + | 14 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 6 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 5| 5| 5| 6| 5| 5| 6| 5| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 3125 PPM | 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 1| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Gallbladder | + | 1 | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Hepatocyte, Necrosis, Focal | 1 | 1 1.0| |__________________________________________________________________________|____________| Pancreas | + | 1 | |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 1 1 1 1 1 1 1 1 1 1 2 1 3 1 | 15 1.2| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Pituitary Gland | + + + I + + + + + + + + + I + | 13 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 7 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 5| 5| 5| 6| 5| 5| 6| 5| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 3125 PPM | 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 1| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Uterus | + + + + + + + + + + + + + + + | 15 | Endometrium, Hyperplasia, Cystic | 2 2 2 1 2 2 2 2 2 2 2 2 2 | 13 1.9| _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 1 2 | 2 1.5| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | Atrophy, Focal | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Trachea | + + | 2 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 8 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 5| 5| 5| 6| 5| 5| 6| 5| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 3125 PPM | 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 1| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | Renal Tubule, Dilatation, Diffuse | 2 | 1 2.0| Renal Tubule, Dilatation, Focal | 1 1 1 1 1 1 1 | 7 1.0| __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 9 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 1| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 1| 0| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 6| 6| 6| 6| 6| 8| 6| 6| 5| 6| 6| 5| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 6250 PPM | 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| 2| 2| 2| 2| 2| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Intestine Large, Cecum | A + | 1 | |__________________________________________________________________________|____________| Intestine Small, Jejunum | A | | |__________________________________________________________________________|____________| Intestine Small, Ileum | A | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + A A + + + + + + + + | 13 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + A A + + + + + + + + | 13 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | Myocardium, Necrosis, Focal | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + A A + + + + + + + + | 13 | Subcapsular, Hyperplasia, Focal | 1 1 3 1 1 1 2 2 1 1 1 2 | 12 1.4| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + A A + + + + + + + + | 13 | |__________________________________________________________________________|____________| Pituitary Gland | + + + + + I I + + + + + + + + | 13 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | |__________________________________________________________________________|____________| Tissue NOS | + | 1 | Abdominal, Fat, Hemorrhage, Focal | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 10 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 1| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 1| 0| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 6| 6| 6| 6| 6| 8| 6| 6| 5| 6| 6| 5| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 6250 PPM | 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| 2| 2| 2| 2| 2| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Uterus | + + + + + + + + + + + + + + + | 15 | Endometrium, Hyperplasia, Cystic | 2 2 2 2 2 2 2 2 2 2 2 2 2 | 13 2.0| _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + A A + + + + + + + + | 13 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + A + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + A A + + + I + + + + | 12 | |__________________________________________________________________________|____________| Spleen | + + + + + A + + + + + + + + + | 14 | Hematopoietic Cell Proliferation | 1 1 3 2 | 4 1.8| |__________________________________________________________________________|____________| Thymus | + + + + + A + + + + + + + + + | 14 | Atrophy, Focal | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + A + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + A + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 11 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 1| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 1| 0| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 6| 6| 6| 6| 6| 8| 6| 6| 5| 6| 6| 5| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 6250 PPM | 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| 2| 2| 2| 2| 2| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + A A + + + + + + + + | 13 | Renal Tubule, Dilatation, Focal | 1 1 1 1 1 | 5 1.0| |__________________________________________________________________________|____________| Urinary Bladder | + | 1 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 12 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 6| 6| 6| 5| 6| 6| 6| 6| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 12500 | 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 1 1 1 1 1 1 2 2 1 1 1 1 1 1 | 15 1.1| |__________________________________________________________________________|____________| Adrenal Medulla | M + + M + + + + + + + + + + + | 13 | |__________________________________________________________________________|____________| Pituitary Gland | + + I + + + + + + + M + + + I | 12 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | Ectopic Thymus | 1 1 | 2 1.0| _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | Cyst | X | 1 | |__________________________________________________________________________|____________| Uterus | + + + + + + + + + + + + + + + | 15 | Endometrium, Hyperplasia, Cystic | 2 2 2 2 2 2 2 2 2 2 2 3 2 2 2 | 15 2.1| _____________________________________________________________________________________________________________________| | * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 13 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 6| 6| 6| 5| 6| 6| 6| 6| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 12500 | 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + I + + + + + + + + M + | 13 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Accessory Spleen | 2 | 1 2.0| Hematopoietic Cell Proliferation | 2 2 2 | 3 2.0| |__________________________________________________________________________|____________| Thymus | M + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 14 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 6| 6| 6| 5| 6| 6| 6| 6| 6| 6| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 12500 | 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM - cont | | | Renal Tubule, Dilatation, Focal | 1 1 1 1 1 | 5 1.0| __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 15 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 6| 6| 6| 6| 5| 5| 6| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 25000 | 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Necrosis, Focal | 1 | 1 1.0| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Accessory Adrenal Cortical Nodule | 1 | 1 1.0| Subcapsular, Hyperplasia, Focal | 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 | 15 1.1| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Pituitary Gland | + + I I + I + + M + + + + + + | 11 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Uterus | + + + + + + + + + + + + + + + | 15 | Endometrium, Hyperplasia, Cystic | 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 | 15 1.9| _____________________________________________________________________________________________________________________| | * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 16 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 6| 6| 6| 6| 5| 5| 6| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 25000 | 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + M I + + + + + + + + + + M + | 12 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 2 2 | 2 2.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | Renal Tubule, Dilatation, Diffuse | 2 | 1 2.0| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 17 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 5| 5| 6| 5| 6| 6| 6| 6| 6| 5| 5| 6| 6| 5| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 25000 | 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| 5| 5| 5| 5| 5| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM - cont | | | Renal Tubule, Dilatation, Focal | 1 1 1 1 1 | 5 1.0| __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 18 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 7| 5| 6| 6| 5| 6| 6| 6| 5| 5| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 50000 | 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| 6| 6| 6| 6| 7| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Esophagus | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Gallbladder | + + + + + M + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Intestine Large, Colon | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Rectum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Cecum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Duodenum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Jejunum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Ileum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 1 3 | 2 2.0| Infiltration Cellular, Focal, | | | Lymphocyte | 1 | 1 1.0| Necrosis, Focal | 1 1 | 2 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 1 | 2 1.0| |__________________________________________________________________________|____________| Pancreas | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Salivary Glands | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 1 1 1 1 | 5 1.0| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 19 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 7| 5| 6| 6| 5| 6| 6| 6| 5| 5| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 50000 | 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| 6| 6| 6| 6| 7| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM - cont | | | |__________________________________________________________________________|____________| Tongue | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Blood Vessel | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 1 1 1 1 1 1 1 1 1 3 1 1 1 1 | 15 1.1| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Islets, Pancreatic | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Parathyroid Gland | M M + + + M M M M M M M M + M | 4 | |__________________________________________________________________________|____________| Pituitary Gland | + + + + + + I M + + + + M + + | 12 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Clitoral Gland | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Ovary | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Uterus | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 20 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 7| 5| 6| 6| 5| 6| 6| 6| 5| 5| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 50000 | 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| 6| 6| 6| 6| 7| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Endometrium, Hyperplasia, Cystic | 1 2 2 2 2 2 2 2 2 2 2 2 2 2 | 14 1.9| |__________________________________________________________________________|____________| Vagina | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Bone Marrow | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | Hyperplasia | 2 | 1 2.0| |__________________________________________________________________________|____________| Lymph Node, Mesenteric | M + + + + + + + + + + + + + + | 14 | Hyperplasia, Histiocytic | 3 | 1 3.0| |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + M + + + M + M + + + | 12 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 2 1 3 | 3 2.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Skin | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | |__________________________________________________________________________|____________| Bone | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Skeletal Muscle | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 21 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 7| 5| 6| 6| 5| 6| 6| 6| 5| 5| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 50000 | 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| 6| 6| 6| 6| 7| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| NERVOUS SYSTEM - cont | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Peripheral Nerve | + | 1 | |__________________________________________________________________________|____________| Spinal Cord | + | 1 | Vacuolization Cytoplasmic | 3 | 1 3.0| _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Larynx | I M + I I I I I + M + I I + + | 5 | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Nose | + + + + + + + + + + + + + + + | 15 | Olfactory Epithelium, Atrophy | 1 | 1 1.0| Olfactory Epithelium, Hyaline Droplet| 2 1 2 | 3 1.7| Respiratory Epithelium, Hyaline | | | Droplet | 2 1 | 2 1.5| |__________________________________________________________________________|____________| Trachea | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | |__________________________________________________________________________|____________| Eye | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Harderian Gland | + + + + + + + + + + + + + + + | 15 | Hyperplasia | 3 | 1 3.0| Infiltration Cellular, Lymphocyte | 1 | 1 1.0| |__________________________________________________________________________|____________| Zymbal's Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 22 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 6| 6| 5| 5| 7| 5| 6| 6| 5| 6| 6| 6| 5| 5| 6| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) FEMALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| 5| | A | 50000 | 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| 6| 6| 6| 6| 7| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM - cont | | | Kidney | + + + + + + + + + + + + + + + | 15 | Nephropathy | 1 | 1 1.0| Glomerulus, Hyalinization | 2 | 1 2.0| Renal Tubule, Dilatation, Focal | 1 1 1 1 1 1 1 1 1 | 9 1.0| |__________________________________________________________________________|____________| Urinary Bladder | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 23 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 6| 7| 7| 7| 7| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 3| 4| 5| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 9| 9| 9| 9| 9| 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Esophagus | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Gallbladder | + + + + + + + + + + + + I + + | 14 | |__________________________________________________________________________|____________| Intestine Large, Colon | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Rectum | + + + M + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Intestine Large, Cecum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Duodenum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Jejunum | + + + + + + + A + + A + + + + | 13 | |__________________________________________________________________________|____________| Intestine Small, Ileum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 1 1 | 3 1.0| Inflammation, Acute | 1 1 | 2 1.0| Necrosis, Focal | 1 2 | 2 1.5| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 1 1 1 1 1 | 6 1.0| |__________________________________________________________________________|____________| Pancreas | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Salivary Glands | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 1 1 1 1 1 1 1 1 1 1 1 | 12 1.0| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 24 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 6| 7| 7| 7| 7| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 3| 4| 5| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 9| 9| 9| 9| 9| 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM - cont | | | |__________________________________________________________________________|____________| Tongue | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Blood Vessel | + + + + + + + + + I + + + + + | 14 | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 1 | 2 1.0| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Islets, Pancreatic | + + + M + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Parathyroid Gland | M + + M M M + + + + M + M M + | 8 | |__________________________________________________________________________|____________| Pituitary Gland | + + I + + + + + + + + + I + + | 13 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + M + | 14 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | Bilateral, Spermatozoa, Degeneration | 1 | 1 1.0| |__________________________________________________________________________|____________| Preputial Gland | + + + + + + + M + + + + + + + | 14 | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 25 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 6| 7| 7| 7| 7| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 3| 4| 5| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 9| 9| 9| 9| 9| 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Prostate | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Seminal Vesicle | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Testes | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Bone Marrow | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | Hyperplasia | 2 | 1 2.0| Necrosis | 1 | 1 1.0| |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + + + M + + M M + + + | 12 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Atrophy, Diffuse | 4 | 1 4.0| Lymphoid Follicle, Atrophy | 1 | 1 1.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | Atrophy, Diffuse | 3 | 1 3.0| Atrophy, Focal | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | |__________________________________________________________________________|____________| Skin | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 26 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 6| 7| 7| 7| 7| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 3| 4| 5| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 9| 9| 9| 9| 9| 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| MUSCULOSKELETAL SYSTEM - cont | | | Bone | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Skeletal Muscle | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | Cerebellum, Medulla, Vacuolization | | | Cytoplasmic | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Larynx | + M M M M M M M M M I M M + M | 2 | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Nose | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Trachea | + + + + + + + + + + + + + M + | 14 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | |__________________________________________________________________________|____________| Eye | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Harderian Gland | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Lymphocyte | 1 1 | 2 1.0| |__________________________________________________________________________|____________| Zymbal's Gland | + + + + + + M + + + M + + + + | 13 | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | Nephropathy | 1 1 | 2 1.0| |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 27 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 6| 7| 7| 7| 7| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 3| 4| 5| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 3| 3| 3| 3| 3| 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| | A | VEHICLE | 9| 9| 9| 9| 9| 9| 9| 9| 9| 0| 0| 0| 0| 0| 0| | L | CONTROL | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM - cont | | | Urinary Bladder | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 28 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 3| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 2| 5| 4| 4| 5| 5| 5| 5| 4| 4| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 3125 PPM | 0| 0| 0| 0| 1| 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Hepatocyte, Necrosis, Focal | 1 | 1 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 2 2 2 2 1 1 2 1 2 1 | 11 1.5| |__________________________________________________________________________|____________| Stomach, Forestomach | A + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Stomach, Glandular | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 | 1 1.0| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Pituitary Gland | + + I + + + I I + I + + + + I | 10 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Prostate | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 29 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 3| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 2| 5| 4| 4| 5| 5| 5| 5| 4| 4| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 3125 PPM | 0| 0| 0| 0| 1| 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Testes | + + + + + + + + + + + + + + + | 15 | Germinal Epithelium, Degeneration | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | M + + + + + + + + I + + + + + | 13 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 2 | 1 2.0| |__________________________________________________________________________|____________| Thymus | M + + + + + + + + + + + + + + | 14 | Atrophy, Focal | 1 1 | 2 1.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | |__________________________________________________________________________|____________| Skeletal Muscle | + | 1 | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | Cerebellum, Medulla, Vacuolization | | | Cytoplasmic | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 30 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 3| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 2| 5| 4| 4| 5| 5| 5| 5| 4| 4| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 3125 PPM | 0| 0| 0| 0| 1| 1| 1| 1| 1| 1| 1| 1| 1| 1| 2| | L | | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| RESPIRATORY SYSTEM - cont | | | Infiltration Cellular, Focal, | | | Lymphocyte | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 31 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 5| 4| 4| 5| 4| 5| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 6250 PPM | 2| 2| 2| 2| 2| 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Necrosis, Focal | 1 1 1 | 3 1.0| Hepatocyte, Necrosis, Focal | 1 | 1 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 1 1 2 1 1 2 1 1 1 2 1 1 1 | 14 1.2| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Pituitary Gland | + I + I + I I + + + + + I + + | 10 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | Inflammation, Chronic Active, Focal | 2 | 1 2.0| |__________________________________________________________________________|____________| Prostate | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 32 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 5| 4| 4| 5| 4| 5| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 6250 PPM | 2| 2| 2| 2| 2| 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | |__________________________________________________________________________|____________| Testes | + + + + + + + + + + + + + + + | 15 | Germinal Epithelium, Degeneration | 2 | 1 2.0| _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | Hyperplasia | 2 2 | 2 2.0| |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + M + + + + M + + + + + + | 13 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 3 3 | 2 3.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | Atrophy, Diffuse | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 33 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 5| 4| 4| 5| 4| 5| 4| 4| 4| 5| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 6250 PPM | 2| 2| 2| 2| 2| 2| 2| 2| 2| 3| 3| 3| 3| 3| 3| | L | | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 34 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 0| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 4| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 4| 5| 4| 4| 4| 5| 4| 4| 5| 4| 4| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 12500 | 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | A + + + + + + + + + + + + + + | 14 | Hepatocyte, Vacuolization | | | Cytoplasmic, Diffuse | 1 | 1 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 1 1 1 1 2 1 1 | 8 1.1| |__________________________________________________________________________|____________| Stomach, Forestomach | A + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Stomach, Glandular | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | A + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Adrenal Medulla | A + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Pituitary Gland | A + + + + + + + I + + I + + + | 12 | |__________________________________________________________________________|____________| Thyroid Gland | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Prostate | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 35 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 0| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 4| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 4| 5| 4| 4| 4| 5| 4| 4| 5| 4| 4| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 12500 | 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Testes | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | A + + + + + + + + + + + + + + | 14 | Hyperplasia | 2 | 1 2.0| |__________________________________________________________________________|____________| Lymph Node, Mesenteric | A + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | A + + + + + + + + + + + + M + | 13 | |__________________________________________________________________________|____________| Spleen | A + + + + + + + + + + + + + + | 14 | Hematopoietic Cell Proliferation | 2 2 2 | 3 2.0| |__________________________________________________________________________|____________| Thymus | A M + + + + + + + + + + + + + | 13 | _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | A + + + + + + + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 36 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 0| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 4| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 4| 5| 4| 4| 4| 5| 4| 4| 5| 4| 4| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 12500 | 3| 3| 3| 3| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 5| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | A + + + + + + + + + + + + + + | 14 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 37 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 2| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 4| 5| 4| 4| 2| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 25000 | 5| 5| 5| 5| 5| 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Necrosis, Focal | 1 | 1 1.0| Hepatocyte, Necrosis, Focal | 1 | 1 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 1 1 1 1 1 1 1 1 1 1 1 1 2 | 13 1.1| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + A | 14 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Subcapsular, Hyperplasia, Focal | 1 | 1 1.0| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Pituitary Gland | + I I + I + + I + + + + + + I | 10 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Prostate | + + M + + + + + + + + + + M + | 13 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 38 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 2| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 4| 5| 4| 4| 2| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 25000 | 5| 5| 5| 5| 5| 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | |__________________________________________________________________________|____________| Testes | + + + + + + + + + + + + + + A | 14 | _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + M | 14 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + A | 14 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + I + + + + + + + M + + | 13 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Atrophy, Diffuse | 4 | 1 4.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | Atrophy, Diffuse | 4 | 1 4.0| Atrophy, Focal | 1 | 1 1.0| _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | None | | | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 39 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 0| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 2| | | | 4| 4| 4| 4| 4| 5| 4| 4| 4| 4| 4| 5| 4| 4| 2| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 25000 | 5| 5| 5| 5| 5| 5| 5| 5| 5| 6| 6| 6| 6| 6| 6| | L | PPM | 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| | | _____________________________________________________________________________________________________________________|____________| URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 40 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 4| 4| 4| 5| 5| 4| 5| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 50000 | 6| 6| 6| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 8| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Esophagus | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Gallbladder | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Colon | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Large, Rectum | + + + + + M + M + + + + + + + | 13 | |__________________________________________________________________________|____________| Intestine Large, Cecum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Duodenum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Jejunum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Intestine Small, Ileum | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Liver | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 | 1 1.0| Necrosis, Focal | 2 1 1 1 | 4 1.3| Hepatocyte, Necrosis, Focal | 1 | 1 1.0| Hepatocyte, Periportal, | | | Vacuolization Cytoplasmic | 2 1 1 1 1 1 2 2 2 2 1 2 2 | 13 1.5| |__________________________________________________________________________|____________| Pancreas | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Salivary Glands | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Focal, | | | Lymphocyte | 1 1 1 1 1 1 1 1 1 1 1 | 11 1.0| |__________________________________________________________________________|____________| Stomach, Forestomach | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Stomach, Glandular | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 41 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 4| 4| 4| 5| 5| 4| 5| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 50000 | 6| 6| 6| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 8| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| ALIMENTARY SYSTEM - cont | | | |__________________________________________________________________________|____________| Tongue | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | CARDIOVASCULAR SYSTEM | | | |__________________________________________________________________________|____________| Blood Vessel | + + + M + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| Heart | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | ENDOCRINE SYSTEM | | | |__________________________________________________________________________|____________| Adrenal Cortex | + + + + + + + + + + + + + + + | 15 | Accessory Adrenal Cortical Nodule | 1 | 1 1.0| Subcapsular, Hyperplasia, Focal | 1 1 1 1 | 4 1.0| |__________________________________________________________________________|____________| Adrenal Medulla | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Islets, Pancreatic | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Parathyroid Gland | M + + M M + M M + + M + M + + | 8 | |__________________________________________________________________________|____________| Pituitary Gland | + + + + + I + I + + + + + I I | 11 | |__________________________________________________________________________|____________| Thyroid Gland | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | GENERAL BODY SYSTEM | | | None | | | _____________________________________________________________________________________________________________________| | GENITAL SYSTEM | | | |__________________________________________________________________________|____________| Epididymis | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Preputial Gland | M + + + + + + + + + + + + + + | 14 | |__________________________________________________________________________|____________| _____________________________________________________________________________________________________________________|____________| * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 42 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 4| 4| 4| 5| 5| 4| 5| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 50000 | 6| 6| 6| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 8| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| GENITAL SYSTEM - cont | | | Prostate | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Seminal Vesicle | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Testes | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | HEMATOPOIETIC SYSTEM | | | |__________________________________________________________________________|____________| Bone Marrow | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mandibular | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mesenteric | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Lymph Node, Mediastinal | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Spleen | + + + + + + + + + + + + + + + | 15 | Hematopoietic Cell Proliferation | 4 | 1 4.0| Pigmentation | 1 | 1 1.0| |__________________________________________________________________________|____________| Thymus | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | INTEGUMENTARY SYSTEM | | | |__________________________________________________________________________|____________| Mammary Gland | M M M M M M M M M M M M M M M | | |__________________________________________________________________________|____________| Skin | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | MUSCULOSKELETAL SYSTEM | | | |__________________________________________________________________________|____________| Bone | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Skeletal Muscle | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 43 NTP Experiment-Test: 99033-03 NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL Report: PEIRPT09 Study Type: SUBCHRON 26-WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03 Route: DOSED FEED Time: 11:43:21 __________________________________________________________________________________________________________________________________ | 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| 2| | | DAY ON TEST | 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| | | | 5| 4| 5| 4| 4| 4| 4| 5| 5| 4| 5| 5| 4| 4| 4| | | __________________________________________|__________________________________________________________________________| T (*) | | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | O | P16(INK4A)/(+/-) (C57BL/6) MALE | 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| 0| | T | ANIMAL ID | 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| 4| | A | 50000 | 6| 6| 6| 6| 7| 7| 7| 7| 7| 7| 7| 7| 7| 7| 8| | L | PPM | 6| 7| 8| 9| 0| 1| 2| 3| 4| 5| 6| 7| 8| 9| 0| | | _____________________________________________________________________________________________________________________|____________| NERVOUS SYSTEM | | | |__________________________________________________________________________|____________| Brain | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | RESPIRATORY SYSTEM | | | |__________________________________________________________________________|____________| Larynx | I + I M M + M M M M M I I M + | 3 | |__________________________________________________________________________|____________| Lung | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Nose | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Trachea | + + + + + + + + + + + + + + + | 15 | _____________________________________________________________________________________________________________________| | SPECIAL SENSES SYSTEM | | | |__________________________________________________________________________|____________| Eye | + + + + + + + + + + + + + + + | 15 | |__________________________________________________________________________|____________| Harderian Gland | + + + + + + + + + + + + + + + | 15 | Infiltration Cellular, Lymphocyte | 1 1 | 2 1.0| |__________________________________________________________________________|____________| Zymbal's Gland | + + + + + + M + + + + + + + + | 14 | _____________________________________________________________________________________________________________________| | URINARY SYSTEM | | | |__________________________________________________________________________|____________| Kidney | + + + + + + + + + + + + + + + | 15 | Nephropathy | 1 1 1 1 1 1 1 | 7 1.0| |__________________________________________________________________________|____________| Urinary Bladder | + + + + + + + + + + + + + + + | 15 | __________________________________________________________________________________________________________________________________ * : Total animals with tissue examined microscopically; total animals with lesion and mean severity grade + : Tissue examined microscopically M : Missing tissue 1-4 : Lesion qualified as: X : Lesion present but not qualified A : Autolysis precludes examination 1) Minimal 3) Moderate I : Insufficient tissue BLANK : Not examined 2) Mild 4) Marked Page 44 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------