National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/13052

TDMS Study 99033-03 Pathology Tables

NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56

                                                      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

































a  Number of animals examined microscopically at site and number of animals with lesion
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)

                                                              Page   1


NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (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                                                                                                                      
    Natural Death                                      2                         2                                                  
    Moribund Sacrifice                                                                                                  1           
  Survivors                                                                                                                         
    Terminal Sacrifice                                13           15           13           15           15           14           
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15           15           
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Liver                                              (15)         (15)         (15)         (15)         (15)         (15)         
      Hematopoietic Cell Proliferation                                                                                  2 [2.0]     
      Infiltration Cellular, Focal, Lymphocyte                                                                          1 [1.0]     
      Infiltration Cellular, Lymphocyte                1 [2.0]                                                                      
      Inflammation, Chronic Active                     1 [1.0]                                                                      
      Necrosis, Focal                                                                                      1 [1.0]      2 [1.0]     
      Hepatocyte, Necrosis, Focal                                   1 [1.0]                                                         
      Hepatocyte, Periportal, Vacuolization                                                                                         
        Cytoplasmic                                                                                                     2 [1.0]     
   Salivary Glands                                    (15)                                                             (15)         
      Infiltration Cellular, Focal, Lymphocyte         4 [1.0]                                                          5 [1.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (15)         (15)         (15)         (15)         (15)         (15)         
      Myocardium, Necrosis, Focal                                                1 [1.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (15)         (15)         (13)         (15)         (15)         (15)         
      Accessory Adrenal Cortical Nodule                                                                    1 [1.0]                  
      Subcapsular, Hyperplasia, Focal                 14 [1.1]     15 [1.2]     12 [1.4]     15 [1.1]     15 [1.1]     15 [1.1]     
   Thyroid Gland                                      (15)         (15)         (15)         (15)         (15)         (15)         
      Ectopic Thymus                                                                          2 [1.0]                               
      Ultimobranchial Cyst                             1                                                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) FEMALE            VEHICLE      3125 PPM     6250 PPM     12500        25000        50000        
                                                      CONTROL                                PPM          PPM          PPM          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   Tissue NOS                                                                   (1)                                                 
      Abdominal, Fat, Hemorrhage, Focal                                          1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Ovary                                              (15)         (15)         (15)         (15)         (15)         (15)         
      Cyst                                                                                    1                                     
   Uterus                                             (15)         (15)         (15)         (15)         (15)         (15)         
      Endometrium, Hyperplasia, Cystic                14 [1.9]     13 [1.9]     13 [2.0]     15 [2.1]     15 [1.9]     14 [1.9]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Lymph Node, Mandibular                             (14)         (15)         (13)         (15)         (15)         (15)         
      Hyperplasia                                                                                                       1 [2.0]     
      Inflammation, Chronic Active                     1 [3.0]                                                                      
   Lymph Node, Mesenteric                             (14)         (15)         (14)         (15)         (15)         (14)         
      Hyperplasia, Histiocytic                                                                                          1 [3.0]     
   Spleen                                             (15)         (15)         (14)         (15)         (15)         (15)         
      Accessory Spleen                                                                        1 [2.0]                               
      Hematopoietic Cell Proliferation                 5 [2.2]      2 [1.5]      4 [1.8]      3 [2.0]      2 [2.0]      3 [2.0]     
      Pigmentation                                     1 [1.0]                                                                      
   Thymus                                             (14)         (15)         (14)         (14)         (15)         (15)         
      Atrophy, Diffuse                                 1 [1.0]                                                                      
      Atrophy, Focal                                                1 [2.0]      1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (15)                                                             (15)         
      Cranium, Osteoporosis                            1 [1.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (15)         (14)         (14)         (15)         (15)         (15)         
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) FEMALE            VEHICLE      3125 PPM     6250 PPM     12500        25000        50000        
                                                      CONTROL                                PPM          PPM          PPM          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
NERVOUS SYSTEM - CONT                                                                                                               
      Granuloma                                        1 [2.0]                                                                      
      Cerebellum, Medulla, Vacuolization                                                                                            
        Cytoplasmic                                    1 [1.0]                                                                      
   Spinal Cord                                                                                                         (1)          
      Vacuolization Cytoplasmic                                                                                         1 [3.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (14)         (14)         (15)         (15)         (15)         
      Alveolar Epithelium, Hyperplasia, Focal          1 [1.0]                                                                      
      Alveolus, Crystals                               1 [4.0]                                                                      
   Nose                                               (15)                                                             (15)         
      Olfactory Epithelium, Atrophy                                                                                     1 [1.0]     
      Olfactory Epithelium, Hyaline Droplet            2 [2.0]                                                          3 [1.7]     
      Respiratory Epithelium, Hyaline Droplet          1 [2.0]                                                          2 [1.5]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (14)                                                             (15)         
      Cataract                                         1                                                                            
   Harderian Gland                                    (15)                                                             (15)         
      Hyperplasia                                                                                                       1 [3.0]     
      Infiltration Cellular, Lymphocyte                                                                                 1 [1.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (15)         (15)         (13)         (15)         (15)         (15)         
      Nephropathy                                      1 [1.0]                                                          1 [1.0]     
      Glomerulus, Hyalinization                                                                                         1 [2.0]     
      Renal Tubule, Dilatation, Diffuse                1 [2.0]      1 [2.0]                                1 [2.0]                  
      Renal Tubule, Dilatation, Focal                 10 [1.0]      7 [1.0]      5 [1.0]      5 [1.0]      5 [1.0]      9 [1.0]     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (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            1                        
  Survivors                                                                                                                         
    Terminal Sacrifice                                14           14           15           14           14           15           
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15           15           
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Liver                                              (15)         (15)         (15)         (14)         (15)         (15)         
      Infiltration Cellular, Focal, Lymphocyte         3 [1.0]                                                          1 [1.0]     
      Inflammation, Acute                              2 [1.0]                                                                      
      Necrosis, Focal                                  2 [1.5]                   3 [1.0]                   1 [1.0]      4 [1.3]     
      Hepatocyte, Necrosis, Focal                                   1 [1.0]      1 [1.0]                   1 [1.0]      1 [1.0]     
      Hepatocyte, Vacuolization Cytoplasmic,                                                                                        
        Diffuse                                                                               1 [1.0]                               
      Hepatocyte, Periportal, Vacuolization                                                                                         
        Cytoplasmic                                    6 [1.0]     11 [1.5]     14 [1.2]      8 [1.1]     13 [1.1]     13 [1.5]     
   Salivary Glands                                    (15)                                                             (15)         
      Infiltration Cellular, Focal, Lymphocyte        12 [1.0]                                                         11 [1.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (15)         (15)         (15)         (14)         (15)         (15)         
      Accessory Adrenal Cortical Nodule                                                                                 1 [1.0]     
      Subcapsular, Hyperplasia, Focal                  2 [1.0]      1 [1.0]                                1 [1.0]      4 [1.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) MALE              VEHICLE      3125 PPM     6250 PPM     12500        25000        50000        
                                                      CONTROL                                PPM          PPM          PPM          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (15)         (15)         (15)         (15)         (15)         (15)         
      Inflammation, Chronic Active, Focal                                        1 [2.0]                                            
      Bilateral, Spermatozoa, Degeneration             1 [1.0]                                                                      
   Testes                                             (15)         (15)         (15)         (14)         (14)         (15)         
      Germinal Epithelium, Degeneration                             1 [2.0]      1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Lymph Node, Mandibular                             (15)         (15)         (15)         (14)         (14)         (15)         
      Hyperplasia                                      1 [2.0]                                1 [2.0]                               
      Necrosis                                         1 [1.0]                                                                      
   Lymph Node, Mesenteric                             (15)         (15)         (15)         (14)         (14)         (15)         
      Hyperplasia                                                                2 [2.0]                                            
   Spleen                                             (15)         (15)         (15)         (14)         (15)         (15)         
      Atrophy, Diffuse                                 1 [4.0]                                             1 [4.0]                  
      Hematopoietic Cell Proliferation                              1 [2.0]      2 [3.0]      3 [2.0]                   1 [4.0]     
      Pigmentation                                                                                                      1 [1.0]     
      Lymphoid Follicle, Atrophy                       1 [1.0]                                                                      
   Thymus                                             (15)         (14)         (15)         (13)         (15)         (15)         
      Atrophy, Diffuse                                 1 [3.0]                   1 [1.0]                   1 [4.0]                  
      Atrophy, Focal                                   1 [2.0]      2 [1.0]                                1 [1.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (15)         (15)         (15)         (14)         (15)         (15)         
      Cerebellum, Medulla, Vacuolization                                                                                            
        Cytoplasmic                                    1 [1.0]      1 [1.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 99033-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/05/03    
Route: DOSED FEED                                 TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      Time: 11:45:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) MALE              VEHICLE      3125 PPM     6250 PPM     12500        25000        50000        
                                                      CONTROL                                PPM          PPM          PPM          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (15)         (15)         (15)         (15)         (15)         
      Infiltration Cellular, Focal, Lymphocyte                      1 [1.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Harderian Gland                                    (15)                                                             (15)         
      Infiltration Cellular, Lymphocyte                2 [1.0]                                                          2 [1.0]     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (15)         (15)         (15)         (14)         (15)         (15)         
      Nephropathy                                      2 [1.0]                                                          7 [1.0]     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
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NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.