TDMS Study 99033-01 Pathology Tables
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
FINAL #3 TG.AC 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 001 VEHICLE CONTROL
Include 002 3125 PPM
Include 003 6250 PPM
Include 004 12500 PPM
Include 005 25000 PPM
Include 006 50000 PPM
Include 008 VEHICLE CONTROL
Include 009 3125 PPM
Include 010 6250 PPM
Include 011 12500 PPM
Include 012 25000 PPM
Include 013 50000 PPM
a Number of animals examined microscopically at site and number of animals with lesion
Page 1
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS FEMALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 15 15 15 15 15 15
Early Deaths
Moribund Sacrifice 3 2 3 4 3 2
Natural Death 1 3 3 2 1 5
Survivors
Terminal Sacrifice 11 10 9 9 11 8
Animals Examined Microscopically 15 15 15 15 15 15
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Gallbladder (14) (6)
Inflammation, Chronic Active 1 (7%)
Liver (15) (15) (14) (15) (14) (14)
Infiltration Cellular, Focal, Lymphocyte 1 (7%)
Infiltration Cellular, Focal,
Polymorphonuclear 1 (7%)
Inflammation, Acute, Focal 1 (7%) 1 (7%) 2 (14%)
Inflammation, Chronic Active, Focal 2 (13%) 1 (7%) 1 (7%)
Necrosis 1 (7%)
Necrosis, Focal 1 (7%) 4 (29%)
Hepatocyte, Necrosis, Focal 1 (7%) 4 (27%) 1 (7%)
Stomach, Forestomach (15) (13) (13) (15) (14) (11)
Infiltration Cellular, Focal, Lymphocyte 1 (8%)
Muscularis, Inflammation, Acute, Focal 1 (8%)
Tongue (15) (15)
Ulcer 1 (7%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
None
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (15) (12) (13) (13) (14) (15)
Accessory Adrenal Cortical Nodule 1 (7%)
Atrophy 3 (20%) 2 (17%) 1 (8%) 4 (31%) 5 (36%) 5 (33%)
Capsule, Inflammation, Acute, Focal 1 (7%)
Subcapsular, Hyperplasia, Focal 12 (80%) 6 (50%) 6 (46%) 5 (38%) 6 (43%) 6 (40%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS FEMALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Zona Reticularis, Vacuolization Cytoplasmic 12 (80%) 9 (75%) 6 (46%) 8 (62%) 9 (64%) 8 (53%)
Pituitary Gland (13) (11) (12) (10) (11) (9)
Cyst 2 (15%)
Pars Intermedia, Hypertrophy 1 (9%)
Thyroid Gland (15) (13) (12) (15) (14) (11)
Follicle, Cyst 1 (7%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (2)
Pigmentation 1 (50%)
Abdominal, Fat, Necrosis, Focal 1 (50%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Ovary (15) (15) (13) (14) (14) (14)
Atrophy 2 (13%) 1 (8%)
Cyst, Focal 1 (7%)
Hemorrhage, Focal 1 (7%)
Uterus (15) (13) (13) (12) (14) (14)
Cyst, Focal 1 (8%)
Hydrometra 1 (7%)
Endometrium, Hyperplasia, Cystic 10 (67%) 8 (62%) 9 (69%) 10 (83%) 10 (71%) 10 (71%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Lymph Node (1) (1)
Renal, Hyperplasia 1 (100%)
Lymph Node, Mandibular (15) (14) (12) (12) (14) (12)
Hyperplasia 2 (14%) 2 (17%) 2 (14%)
Hyperplasia, Plasma Cell 2 (13%) 1 (8%)
Inflammation, Acute, Focal 1 (7%)
Lymph Node, Mediastinal (12) (11) (11) (12) (11) (11)
Hyperplasia 1 (8%) 1 (9%)
Spleen (15) (14) (14) (12) (14) (14)
Accessory Spleen 1 (7%)
Hematopoietic Cell Proliferation 10 (67%) 4 (29%) 7 (50%) 6 (50%) 8 (57%) 5 (36%)
Pigmentation 10 (67%) 10 (71%) 11 (79%) 10 (83%) 11 (79%) 9 (64%)
Thymus (15) (13) (12) (12) (13) (11)
Atrophy, Diffuse 3 (20%) 1 (8%) 1 (8%) 2 (17%) 2 (15%) 2 (18%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS FEMALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Atrophy, Focal 2 (13%) 1 (8%) 1 (8%) 1 (9%)
Hyperplasia, Diffuse 1 (8%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (15) (3) (1) (3) (15)
Lip, Control Epidermis, Hyperplasia, Focal 1 (33%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (15) (12) (13) (13) (14) (11)
Abscess, Focal 1 (7%)
Inflammation, Acute, Focal 1 (7%)
Cerebellum, Corpus Callosum, Pons,
Vacuolization Cytoplasmic, Focal 1 (8%)
Cortex, Cerebrum, Degeneration, Focal 1 (9%)
Cortex, Cerebrum, Neuron, Necrosis 1 (8%)
Medulla, Vacuolization Cytoplasmic 1 (7%)
Pyramidal Cell, Hippocampus, Necrosis 1 (8%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (15) (14) (14) (15) (14) (14)
Hemorrhage, Focal 1 (7%)
Infiltration Cellular, Focal, Lymphocyte 1 (7%)
Inflammation, Chronic Active, Focal 1 (7%)
Alveolar Epithelium, Hyperplasia, Focal 1 (7%) 1 (7%)
Perivascular, Infiltration Cellular,
Lymphocyte 1 (7%) 1 (7%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (15) (10)
Retina, Atrophy 15 (100%) 10 (100%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS FEMALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Harderian Gland (15) (15)
Inflammation, Chronic Active 1 (7%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (15) (12) (13) (14) (14) (14)
Infiltration Cellular, Focal, Lymphocyte 1 (7%)
Inflammation, Acute, Focal 1 (7%)
Mineralization, Focal 1 (7%)
Nephropathy 1 (7%) 1 (7%)
Renal Tubule, Dilatation, Focal 1 (7%) 2 (17%) 1 (8%) 1 (7%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS MALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 15 15 15 15 15 15
Early Deaths
Natural Death 3 3 1 1 1
Moribund Sacrifice 3 3 4 2 3 4
Survivors
Terminal Sacrifice 9 12 8 12 11 10
Animals Examined Microscopically 15 15 15 15 15 15
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Liver (15) (15) (14) (15) (14) (15)
Hematopoietic Cell Proliferation 1 (7%) 1 (7%)
Infiltration Cellular, Focal, Lymphocyte 1 (7%) 1 (7%)
Inflammation, Acute, Focal 1 (7%)
Necrosis, Focal 2 (13%)
Stomach, Forestomach (12) (15) (13) (14) (14) (14)
Epithelium, Hyperplasia 1 (8%)
Stomach, Glandular (12) (15) (13) (14) (14) (14)
Inflammation, Acute 1 (7%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
None
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (13) (15) (13) (14) (15) (13)
Atrophy 10 (77%) 12 (80%) 8 (62%) 9 (64%) 8 (53%) 6 (46%)
Hypertrophy, Focal 9 (69%) 5 (33%) 5 (38%) 6 (43%) 7 (47%) 5 (38%)
Subcapsular, Hyperplasia, Focal 1 (8%)
Thyroid Gland (13) (15) (13) (14) (14) (14)
Follicle, Cyst 2 (15%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS MALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Coagulating Gland (1) (1)
Cyst 1 (100%)
Epididymis (15) (15) (15) (15) (15) (15)
Bilateral, Aspermia 1 (7%)
Bilateral, Spermatozoa, Degeneration 1 (7%) 1 (7%)
Unilateral, Aspermia 1 (7%) 3 (20%) 4 (27%) 2 (13%) 3 (20%) 2 (13%)
Unilateral, Cyst 1 (7%) 1 (7%) 1 (7%)
Unilateral, Inflammation, Chronic Active 2 (13%)
Unilateral, Duct, Hyperplasia, Regenerative 1 (7%) 1 (7%)
Unilateral, Spermatozoa, Degeneration 1 (7%)
Preputial Gland (12) (1) (1) (12)
Cyst 1 (8%) 1 (100%) 1 (100%)
Prostate (13) (15) (15) (15) (15) (14)
Inflammation, Acute, Focal 1 (7%)
Seminal Vesicle (13) (1) (14)
Dilatation 1 (100%)
Testes (15) (15) (15) (14) (15) (15)
Cyst 1 (7%) 1 (7%) 1 (7%)
Bilateral, Germinal Epithelium, Degeneration 2 (13%) 1 (7%) 1 (7%)
Unilateral, Cyst 1 (7%) 2 (13%) 3 (20%) 2 (14%) 2 (13%) 1 (7%)
Unilateral, Germinal Epithelium, Degeneration 1 (7%) 2 (13%) 4 (27%) 2 (14%) 3 (20%) 3 (20%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (14) (14)
Hyperplasia 2 (14%)
Lymph Node, Mandibular (12) (15) (13) (14) (14) (14)
Hyperplasia 2 (13%) 2 (14%)
Hyperplasia, Plasma Cell 1 (8%) 1 (7%)
Necrosis 2 (17%)
Lymph Node, Mesenteric (13) (15) (13) (14) (15) (14)
Hyperplasia 1 (8%)
Necrosis 1 (8%)
Lymph Node, Mediastinal (11) (13) (11) (10) (14) (13)
Hyperplasia 1 (10%)
Spleen (14) (15) (13) (15) (14) (14)
Hematopoietic Cell Proliferation 3 (21%) 3 (20%) 8 (62%) 2 (13%) 8 (57%) 4 (29%)
Pigmentation 9 (64%) 12 (80%) 8 (62%) 12 (80%) 13 (93%) 11 (79%)
Lymphoid Follicle, Depletion Cellular 1 (7%)
Thymus (12) (14) (12) (13) (14) (12)
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 99033-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: 26-39 WEEKS TRANSGENIC MODEL EVALUATION II (ASPARTAME) Date: 03/05/03
Route: DOSED FEED Time: 11:23:35
____________________________________________________________________________________________________________________________________
TGAC (FVB/N) HEMIZYGOUS MALE VEHICLE 3125 PPM 6250 PPM 12500 25000 50000
CONTROL PPM PPM PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Atrophy, Diffuse 1 (8%) 1 (8%) 4 (29%)
Atrophy, Focal 1 (8%) 2 (14%) 2 (17%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (15) (2) (1) (15)
Control Epidermis, Hyperplasia, Focal 1 (100%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (15) (15) (13) (14) (14) (15)
Cortex, Cerebrum, Degeneration, Focal 1 (7%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (14) (15) (14) (15) (14) (14)
Hemorrhage, Focal 3 (20%) 1 (7%)
Alveolar Epithelium, Hyperplasia, Focal 1 (7%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (12) (14)
Retina, Atrophy 12 (100%) 14 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (15) (15) (13) (15) (14) (15)
Dilatation, Diffuse 1 (8%)
Nephropathy 3 (20%) 1 (7%)
Renal Tubule, Cyst 1 (7%)
Renal Tubule, Dilatation, Diffuse 1 (7%) 1 (7%)
Renal Tubule, Dilatation, Focal 1 (7%) 1 (8%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
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