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TDMS Study 99034-01 Pathology Tables

NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19

                                                         FINAL #1 MICE




       Facility:  Battelle Columbus Laboratory

       Chemical CAS #:  71-43-2

       Lock Date:  10/15/01

       Cage Range:  All

       Reasons For Removal:    All

       Removal Date Range:     All

       Treatment Groups:       Include All

































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

                                                              Page   1


NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) FEMALE            0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          15           15           15           15           15                        
  Early Deaths                                                                                                                      
  Survivors                                                                                                                         
    Terminal Sacrifice                                15           15           15           15           15                        
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15                        
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Small, Duodenum                          (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Chronic Active                                                            2 [1.0]                               
   Liver                                              (15)         (15)         (15)         (15)         (15)                      
      Hematopoietic Cell Proliferation                                                        1 [2.0]      1 [1.0]                  
      Inflammation, Chronic                           10 [1.0]      6 [1.0]      6 [1.0]      4 [1.0]     11 [1.0]                  
   Stomach, Forestomach                               (15)         (15)         (15)         (15)         (15)                      
      Erosion                                                                                 1 [2.0]                               
      Hyperplasia                                      1 [1.0]                                                                      
      Inflammation, Chronic                                                      3 [2.0]                                            
   Stomach, Glandular                                 (15)         (15)         (15)         (15)         (15)                      
      Mineralization                                                                                       1 [1.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (15)         (15)         (15)         (15)         (15)                      
      Myocardium, Inflammation, Chronic                                                                    1 [1.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Pituitary Gland                                    (15)         (15)         (15)         (15)         (15)                      
      Infiltration Cellular, Lymphoid                  1 [1.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) FEMALE            0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
GENITAL SYSTEM - CONT                                                                                                               
   Clitoral Gland                                     (1)                                                                           
      Pigmentation                                     1 [3.0]                                                                      
   Ovary                                              (14)         (15)         (15)         (15)         (15)                      
      Angiectasis                                                                                          1 [1.0]                  
      Cyst                                             1 [1.0]                                2 [1.0]      2 [1.0]                  
   Uterus                                             (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Chronic Active                                                                         1 [1.0]                  
      Inflammation, Suppurative                                                  1 [1.0]      1 [1.0]      1 [1.0]                  
      Endometrium, Hyperplasia, Cystic                12 [1.0]     15 [1.1]     15 [1.0]     15 [1.1]     14 [1.1]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Lymph Node                                         (13)         (11)         (11)         (12)         (13)                      
      Lumbar, Hyperplasia, Lymphoid                                                                        1 [3.0]                  
      Lumbar, Pigmentation                                                                                 1 [2.0]                  
      Mediastinal, Atrophy                                                       2 [1.5]      4 [1.3]      2 [1.0]                  
   Lymph Node, Mandibular                             (14)         (15)         (15)         (15)         (15)                      
      Atrophy                                                       1 [1.0]      2 [1.0]      4 [1.0]                               
      Hyperplasia, Lymphoid                            1 [1.0]      4 [1.3]      2 [1.5]      5 [1.4]      3 [1.0]                  
      Infiltration Cellular, Polymorphonuclear         1 [1.0]                                             2 [1.0]                  
   Lymph Node, Mesenteric                             (15)         (15)         (15)         (15)         (15)                      
      Atrophy                                                       2 [2.0]      3 [1.0]      8 [1.8]      6 [1.3]                  
      Hyperplasia, Lymphoid                                                                                1 [2.0]                  
   Spleen                                             (15)         (15)         (15)         (15)         (15)                      
      Hematopoietic Cell Proliferation                 5 [1.0]      5 [1.2]      2 [1.0]      3 [1.3]      7 [1.1]                  
      Infiltration Cellular, Lymphocyte                1 [4.0]                                                                      
      Lymphoid Follicle, Atrophy                                    1 [1.0]      1 [2.0]                   1 [2.0]                  
   Thymus                                             (15)         (15)         (15)         (15)         (15)                      
      Hyperplasia, Atypical                                         1 [2.0]      1 [4.0]      1 [3.0]      1 [2.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (15)         (15)         (15)         (15)         (15)                      
      Hyperplasia                                                                                          2 [1.0]                  
   Skin                                               (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Granulomatous                      1 [1.0]                   1 [2.0]                                            
      Inflammation, Suppurative                                                               1 [1.0]      1 [2.0]                  
      Pigmentation                                                  1 [1.0]      8 [1.0]     15 [1.1]     15 [1.1]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) FEMALE            0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (15)         (15)         (15)         (15)         (15)                      
      Fibrosis                                                                   1 [1.0]      1 [1.0]      1 [1.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Chronic Active                     2 [1.5]      2 [1.0]                                2 [1.0]                  
      Alveolar Epithelium, Hyperplasia, Focal          1 [1.0]                                             3 [1.3]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (15)         (15)         (15)         (15)         (15)                      
      Casts Protein                                    5 [1.0]      4 [1.0]      5 [1.0]      8 [1.0]      7 [1.0]                  
      Infiltration Cellular, Lymphoid                  1 [1.0]                                                                      
      Infiltration Cellular, Lymphocyte                1 [2.0]                                                                      
      Nephropathy                                      3 [1.0]                   1 [1.0]      2 [1.0]      1 [1.0]                  
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) MALE              0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          15           15           15           15           15                        
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                                                                     1                        
  Survivors                                                                                                                         
    Terminal Sacrifice                                15           15           15           15           14                        
                                                                                                                                    
  Animals Examined Microscopically                    15           15           15           15           15                        
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Liver                                              (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Chronic                            3 [1.0]      6 [1.0]      1 [1.0]      3 [1.0]      1 [1.0]                  
   Salivary Glands                                                                           (1)          (1)                       
      Submandibular Gland, Atrophy                                                                         1 [2.0]                  
      Submandibular Gland, Inflammation, Chronic                                              1 [1.0]                               
   Stomach, Forestomach                               (15)         (15)         (15)         (15)         (15)                      
      Erosion                                                                                              1 [3.0]                  
      Hyperplasia                                      1 [1.0]                                             3 [2.0]                  
      Inflammation, Acute                                                                     1 [2.0]                               
   Stomach, Glandular                                 (15)         (15)         (15)         (15)         (15)                      
      Mineralization                                                             1 [1.0]                                            
      Glands, Cyst                                                               1 [1.0]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (15)         (15)         (15)         (15)         (15)                      
      Myocardium, Inflammation, Chronic                             1 [1.0]      1 [1.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) MALE              0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (15)         (15)         (15)         (15)         (15)                      
      Granuloma Sperm                                                                                      1 [2.0]                  
      Unilateral, Hypospermia                          1 [4.0]                                                                      
   Testes                                             (15)         (15)         (15)         (15)         (15)                      
      Germinal Epithelium, Atrophy                                                            1 [2.0]                               
      Germinal Epithelium, Syncytial Alteration                                               1 [1.0]      1 [1.0]                  
      Rete Testes, Inflammation, Granulomatous         1 [2.0]                                                                      
      Unilateral, Germinal Epithelium, Atrophy         1 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (15)         (15)         (15)         (15)         (15)                      
      Atrophy                                                                                10 [1.1]     12 [1.3]                  
      Pigmentation, Hemosiderin                        1 [1.0]     13 [1.0]     13 [1.1]     15 [2.0]     14 [2.9]                  
   Lymph Node                                         (11)         (11)         (12)         (9)          (7)                       
      Mediastinal, Atrophy                                                       2 [1.0]      6 [1.3]      6 [1.7]                  
   Lymph Node, Mandibular                             (15)         (15)         (15)         (14)         (14)                      
      Atrophy                                                                                 6 [1.3]     11 [1.2]                  
      Hyperplasia, Lymphoid                            2 [1.0]      1 [1.0]      1 [1.0]                                            
      Infiltration Cellular, Polymorphonuclear                                                1 [2.0]      1 [1.0]                  
   Lymph Node, Mesenteric                             (15)         (15)         (14)         (15)         (15)                      
      Atrophy                                          1 [1.0]      2 [2.0]      2 [1.0]     13 [2.0]     13 [1.7]                  
      Infiltration Cellular, Polymorphonuclear                                                             1 [2.0]                  
   Spleen                                             (15)         (15)         (15)         (15)         (15)                      
      Hematopoietic Cell Proliferation                              1 [1.0]                   2 [1.0]      8 [1.3]                  
      Lymphoid Follicle, Atrophy                                                             15 [1.8]     14 [2.9]                  
   Thymus                                             (15)         (15)         (15)         (15)         (15)                      
      Atrophy                                                                                 7 [3.0]     13 [2.9]                  
      Mineralization                                                                                       1 [1.0]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (15)         (15)         (15)         (15)         (15)                      
      Pigmentation                                                 15 [1.1]     15 [1.6]     15 [2.3]     14 [2.6]                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (15)         (15)         (15)         (15)         (15)                      
      Pigmentation, Hemosiderin                                                  1 [1.0]                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 99034-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: SUBCHRON 26-WEEK                         WITH AVERAGE SEVERITY GRADES[b]                              Date: 11/05/03    
Route: GAVAGE                                      TRANSGENIC MODEL EVALUATION II (BENZENE)                       Time: 15:01:19    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         P16(INK4A)/(+/-) (C57BL/6) MALE              0 MG/KG      25 MG/KG     50 MG/KG     100          200                       
                                                                                             MG/KG        MG/KG                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (15)         (15)         (15)         (15)         (15)                      
      Inflammation, Chronic Active                     2 [1.0]                   1 [1.0]      3 [1.0]      5 [1.0]                  
      Alveolar Epithelium, Hyperplasia, Focal                                    1 [1.0]                                            
      Bronchiole, Hyperplasia, Focal                                             1 [1.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (15)         (15)         (15)         (15)         (15)                      
      Casts Protein                                    1 [1.0]                   2 [1.0]      1 [1.0]      2 [1.0]                  
      Nephropathy                                      1 [1.0]      1 [1.0]                   2 [1.0]      4 [1.3]                  
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
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