National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/12083

TDMS Study 99033-02 Pathology Tables

NTP Experiment-Test: 99033-02         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: 11:32:25

                                                       FINAL #3/P53 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


































a  Number of animals examined microscopically at site and number of animals with lesion

                                                              Page   1


NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) 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                                 1                         1                                                  
    Natural Death                                                   1                                                               
  Survivors                                                                                                                         
    Terminal Sacrifice                                14           14           14           15           15           15           
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15           15           
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Liver                                              (15)         (15)         (15)         (15)         (15)         (15)         
      Infiltration Cellular, Focal, Lymphocyte         4 (27%)      3 (20%)      4 (27%)      6 (40%)      4 (27%)      4 (27%)     
      Necrosis, Focal                                                                                                   1 (7%)      
      Pigmentation, Focal, Hemosiderin                 1 (7%)                                                                       
      Tension Lipidosis                                1 (7%)                                                                       
      Hepatocyte, Necrosis, Focal                                                                          2 (13%)                  
      Hepatocyte, Vacuolization Cytoplasmic, Focal                                                         1 (7%)                   
   Salivary Glands                                    (15)                                                             (15)         
      Infiltration Cellular, Focal, Lymphocyte         6 (40%)                                                          8 (53%)     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (15)         (15)         (14)         (15)         (15)         (15)         
      Hyperplasia, Focal                                                         1 (7%)       1 (7%)       1 (7%)                   
      Subcapsular, Hyperplasia, Focal                 12 (80%)     13 (87%)     13 (93%)     15 (100%)    15 (100%)    15 (100%)    
   Pituitary Gland                                    (9)          (14)         (13)         (14)         (11)         (14)         
      Pars Intermedia, Hypertrophy                                               1 (8%)                    2 (18%)      2 (14%)     
   Thyroid Gland                                      (14)         (13)         (14)         (14)         (13)         (15)         
      Ectopic Thymus                                   2 (14%)      1 (8%)       1 (7%)       3 (21%)      1 (8%)       2 (13%)     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) FEMALE                    VEHICLE      3125 PPM     6250 PPM     12500        25000        50000           
                                                   CONTROL                                PPM          PPM          PPM             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Ovary                                              (15)         (15)         (14)         (15)         (15)         (15)         
      Atrophy                                                                    1 (7%)                                             
      Cyst                                             1 (7%)                                                                       
   Uterus                                             (15)         (15)         (15)         (15)         (15)         (15)         
      Hydrometra                                                    1 (7%)                                                          
      Endometrium, Hyperplasia, Cystic                14 (93%)     14 (93%)     15 (100%)    14 (93%)     15 (100%)    15 (100%)    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Lymph Node, Mandibular                             (15)         (13)         (13)         (15)         (15)         (14)         
      Congestion                                                                                           1 (7%)                   
      Hyperplasia                                      1 (7%)       2 (15%)                   1 (7%)       1 (7%)                   
      Hyperplasia, Histiocytic                         1 (7%)                                                                       
      Hyperplasia, Lymphoid                            2 (13%)                                                                      
      Hyperplasia, Plasma Cell                         1 (7%)                                                                       
   Lymph Node, Mesenteric                             (15)         (14)         (14)         (14)         (15)         (15)         
      Hyperplasia                                                   1 (7%)                                                          
      Hyperplasia, Lymphoid                            1 (7%)                                                                       
   Lymph Node, Mediastinal                            (12)         (13)         (13)         (12)         (13)         (15)         
      Hyperplasia, Lymphoid                            1 (8%)                                                                       
   Spleen                                             (15)         (15)         (15)         (15)         (15)         (15)         
      Depletion Cellular, Diffuse                                   1 (7%)                                                          
      Hematopoietic Cell Proliferation                 3 (20%)      4 (27%)      1 (7%)       3 (20%)      1 (7%)       1 (7%)      
      Pigmentation                                                                                         1 (7%)                   
   Thymus                                             (14)         (14)         (14)         (15)         (15)         (15)         
      Atrophy, Focal                                   1 (7%)                                                                       
      Hyperplasia                                                                1 (7%)                                 1 (7%)      
      Hyperplasia, Atypical, Focal                                                            1 (7%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (15)                      (1)                                    (15)         
      Femur, Fibrous Osteodystrophy, Focal                                                                              1 (7%)      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) FEMALE                    VEHICLE      3125 PPM     6250 PPM     12500        25000        50000           
                                                   CONTROL                                PPM          PPM          PPM             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (15)         (14)         (14)         (15)         (15)         (15)         
      Medulla, Cyst Epithelial Inclusion                                                      1 (7%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (15)         (14)         (15)         (15)         (15)         
      Infiltration Cellular, Focal, Lymphocyte         1 (7%)                                              1 (7%)       1 (7%)      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Harderian Gland                                    (15)                                                             (15)         
      Infiltration Cellular, Focal, Lymphocyte         1 (7%)                                                           3 (20%)     
      Inflammation, Chronic Active                                                                                      1 (7%)      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (15)         (14)         (15)         (15)         (15)         (15)         
      Infiltration Cellular, Focal, Lymphocyte                      1 (7%)                    1 (7%)                                
      Glomerulus, Hyalinization                                                                                         1 (7%)      
      Renal Tubule, Dilatation, Diffuse                1 (7%)       2 (14%)      3 (20%)                                            
      Renal Tubule, Dilatation, Focal                  6 (40%)      5 (36%)      2 (13%)      5 (33%)      4 (27%)      4 (27%)     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) 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                                      1                         1                         1                        
    Moribund Sacrifice                                                           1                                      1           
  Survivors                                                                                                                         
    Terminal Sacrifice                                14           15           13           15           14           14           
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15           15           
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Liver                                              (15)         (15)         (15)         (15)         (14)         (15)         
      Infiltration Cellular, Focal, Lymphocyte         2 (13%)      2 (13%)      4 (27%)      1 (7%)       2 (14%)      5 (33%)     
      Inflammation, Chronic                            1 (7%)                                                                       
      Inflammation, Chronic Active                     3 (20%)                                                          1 (7%)      
      Necrosis, Focal                                  2 (13%)      1 (7%)                                              1 (7%)      
      Hepatocyte, Periportal, Vacuolization                                                                                         
        Cytoplasmic, Diffuse                           2 (13%)                                                          4 (27%)     
   Salivary Glands                                    (15)         (1)          (1)                       (1)          (15)         
      Infiltration Cellular, Focal, Lymphocyte         9 (60%)      1 (100%)                               1 (100%)    10 (67%)     
   Tooth                                                                                                               (1)          
      Peridontal Tissue, Cyst                                                                                           1 (100%)    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (15)         (15)         (15)         (15)         (15)         (15)         
      Atrophy                                         14 (93%)     14 (93%)     12 (80%)     12 (80%)     10 (67%)     13 (87%)     
      Hypertrophy, Focal                                            1 (7%)       3 (20%)      2 (13%)      1 (7%)       3 (20%)     
      Subcapsular, Hyperplasia, Focal                  1 (7%)                    2 (13%)      1 (7%)       2 (13%)      1 (7%)      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) MALE                      VEHICLE      3125 PPM     6250 PPM     12500        25000        50000           
                                                   CONTROL                                PPM          PPM          PPM             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (15)         (15)         (15)         (15)         (14)         (15)         
      Epithelium, Degeneration, Focal                               1 (7%)                                                          
   Testes                                             (15)         (15)         (15)         (15)         (14)         (15)         
      Mineralization, Focal                                         1 (7%)                                                          
      Germinal Epithelium, Degeneration, Diffuse                    1 (7%)                                                          
      Germinal Epithelium, Degeneration, Focal                      1 (7%)                    1 (7%)                                
      Rete Testes, Inflammation, Focal                 1 (7%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (14)                                                             (15)         
      Hyperplasia                                                                                                       1 (7%)      
   Lymph Node                                                                                (1)                                    
      Iliac, Pigmentation, Focal                                                              1 (100%)                              
   Lymph Node, Mandibular                             (14)         (15)         (14)         (15)         (14)         (15)         
      Hyperplasia                                                   3 (20%)                   2 (13%)                               
      Hyperplasia, Plasma Cell                         1 (7%)                                                           2 (13%)     
   Lymph Node, Mesenteric                             (14)         (14)         (15)         (13)         (14)         (15)         
      Hyperplasia                                                                                          1 (7%)                   
   Lymph Node, Mediastinal                            (13)         (14)         (14)         (13)         (12)         (13)         
      Hyperplasia                                                                                          1 (8%)                   
   Spleen                                             (15)         (15)         (15)         (15)         (14)         (15)         
      Atrophy                                          2 (13%)                                                                      
      Hematopoietic Cell Proliferation                                                                     1 (7%)       2 (13%)     
      Hyperplasia, Lymphoid                                                                                             1 (7%)      
   Thymus                                             (14)         (15)         (15)         (14)         (15)         (14)         
      Atrophy, Diffuse                                                                                     1 (7%)                   
      Atrophy, Focal                                                                                                    2 (14%)     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-02         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: 11:32:25    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P53+/-(C57BL/6) MALE                      VEHICLE      3125 PPM     6250 PPM     12500        25000        50000           
                                                   CONTROL                                PPM          PPM          PPM             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (14)         (15)         (15)         (15)         (14)         (15)         
      Hydrocephalus                                                              1 (7%)                                             
      Corpus Callosum, Medulla, Vacuolization                                                                                       
        Cytoplasmic, Focal                                                       1 (7%)                                             
      Medulla, Vacuolization Cytoplasmic, Focal                                                                         1 (7%)      
      Ventricle, Hydrocephalus                                      1 (7%)                                                          
   Peripheral Nerve                                   (1)                                                                           
      Vacuolization Cytoplasmic, Diffuse               1 (100%)                                                                     
   Spinal Cord                                        (1)                                                                           
      Vacuolization Cytoplasmic, Focal                 1 (100%)                                                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (15)         (15)         (15)         (14)         (15)         
      Infiltration Cellular, Focal, Lymphocyte                                                                          1 (7%)      
      Inflammation, Chronic Active, Diffuse                                      1 (7%)                                             
      Perivascular, Infiltration Cellular,                                                                                          
        Lymphocyte                                                                                         2 (14%)                  
   Nose                                               (14)                                                             (15)         
      Inflammation, Acute                              1 (7%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (14)                      (1)                                    (15)         
      Developmental Malformation                                                 1 (100%)                                           
   Harderian Gland                                    (15)                                                             (15)         
      Infiltration Cellular, Focal, Lymphocyte         5 (33%)                                                          1 (7%)      
      Inflammation, Chronic Active                                                                                      1 (7%)      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (14)         (15)         (15)         (15)         (14)         (15)         
      Infiltration Cellular, Focal, Lymphocyte                      1 (7%)                    1 (7%)                                
      Nephropathy                                      4 (29%)                                                          3 (20%)     
      Renal Tubule, Dilatation, Diffuse                             2 (13%)                   1 (7%)                    1 (7%)      
      Renal Tubule, Dilatation, Focal                               2 (13%)                                                         
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
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