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TDMS Study 99033-03 Pathology Tables

NTP Experiment-Test: 99033-03                  NONNEOPLASTIC LESIONS BY INDIVIDUAL ANIMAL                         Report: PEIRPT09
Study Type: SUBCHRON 26-WEEK                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                        Date: 03/05/03
Route: DOSED FEED                                                                                                 Time: 11:43:21

                                                      FINAL #3 TG:P16 MICE




       Facility:  BIORELIANCE

       Chemical CAS #:  22839-47-0

       Lock Date:  07/20/01

       Cage Range:  All

       Reasons For Removal:    All

       Removal Date Range:     All

       Treatment Groups:       Include All




































                                                              Page   1


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