National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/2304

TDMS Study 05067-10 Pathology Tables

NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96
Route: GAVAGE                                                                                                     Time: 13:10:54

                                                           CORE STUDY




       Facility:  Southern Research Institute

       Chemical CAS #:   58-55-9

       Lock Date:  07/14/93

       Cage Range:  All

       Reasons For Removal:    All

       Removal Date Range:     All

       Treatment Groups:       Include All


































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

                                                              Page   1

NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 7            4           11            9                                     
    Natural Death                                      6            9            5            8                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                37           37           34           33                                     
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Muscularis, Inflammation, Chronic                1 (2%)                                                                       
   Gallbladder                                        (46)         (48)         (47)         (49)                                   
      Inflammation, Chronic                                         1 (2%)                    1 (2%)                                
   Intestine Large, Colon                             (48)         (49)         (47)         (48)                                   
      Inflammation, Chronic                                                                   1 (2%)                                
      Polyp Inflammatory                                                         1 (2%)                                             
   Intestine Large, Cecum                             (48)         (45)         (47)         (47)                                   
      Inflammation, Chronic                                         1 (2%)                                                          
   Intestine Small, Jejunum                           (47)         (46)         (47)         (43)                                   
      Peyer's Patch, Hyperplasia, Lymphoid                          2 (4%)                                                          
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)                    1 (2%)                                             
      Basophilic Focus                                                           1 (2%)       1 (2%)                                
      Eosinophilic Focus                               6 (12%)      7 (14%)      5 (10%)      3 (6%)                                
      Hematopoietic Cell Proliferation                 2 (4%)       1 (2%)       1 (2%)                                             
      Hyperplasia, Focal, Lymphoid                                  1 (2%)       2 (4%)       1 (2%)                                
      Inflammation, Chronic                                         3 (6%)       5 (10%)      2 (4%)                                
      Inflammation, Focal                              1 (2%)                                 1 (2%)                                
      Mixed Cell Focus                                 2 (4%)       1 (2%)       2 (4%)       2 (4%)                                
      Necrosis, Focal                                  2 (4%)       4 (8%)       2 (4%)       1 (2%)                                
      Pigmentation, Focal                                           2 (4%)       1 (2%)                                             
      Vacuolization Cytoplasmic                        6 (12%)      8 (16%)      5 (10%)      2 (4%)                                
      Bile Duct, Cyst                                  1 (2%)                                                                       
      Centrilobular, Necrosis                          1 (2%)       1 (2%)                    1 (2%)                                
      Hepatocyte, Karyomegaly                                                    1 (2%)                                             
   Mesentery                                          (10)         (8)          (6)          (5)                                    
      Hemorrhage                                                    1 (13%)                                                         
      Inflammation, Chronic                                         1 (13%)                                                         
      Fat, Necrosis                                    8 (80%)      4 (50%)      2 (33%)      2 (40%)                               
   Pancreas                                           (50)         (49)         (49)         (49)                                   
      Inflammation, Chronic                                         1 (2%)       1 (2%)                                             
      Necrosis                                         1 (2%)                                                                       
      Acinus, Atrophy, Focal                                                     2 (4%)                                             
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    2                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Duct, Cyst                                       1 (2%)                    3 (6%)                                             
   Salivary Glands                                    (50)         (49)         (50)         (50)                                   
      Fibrosis                                         1 (2%)                    1 (2%)       1 (2%)                                
      Mineralization                                                                          1 (2%)                                
      Vacuolization Cytoplasmic                                     1 (2%)       1 (2%)                                             
   Stomach, Forestomach                               (50)         (49)         (49)         (50)                                   
      Cyst                                                          1 (2%)                                                          
      Edema                                            1 (2%)       1 (2%)                                                          
      Ulcer                                                                      2 (4%)                                             
      Epithelium, Hyperplasia                          6 (12%)      6 (12%)     12 (24%)      5 (10%)                               
   Stomach, Glandular                                 (49)         (49)         (48)         (50)                                   
      Edema                                            1 (2%)                                                                       
      Erosion                                          1 (2%)       1 (2%)                    1 (2%)                                
      Inflammation, Chronic                                         1 (2%)                                                          
      Mineralization                                   4 (8%)       3 (6%)       5 (10%)      9 (18%)                               
      Glands, Degeneration, Cystic, Focal             11 (22%)      5 (10%)      4 (8%)       3 (6%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Blood Vessel                                       (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                                                                   1 (2%)                                
   Heart                                              (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic, Focal                     2 (4%)                    1 (2%)       1 (2%)                                
      Mineralization                                                1 (2%)                    1 (2%)                                
      Thrombosis                                                                              1 (2%)                                
      Artery, Inflammation, Chronic                                 1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (49)         (50)         (50)         (49)                                   
      Accessory Adrenal Cortical Nodule                1 (2%)       1 (2%)                    2 (4%)                                
      Cyst                                             1 (2%)                    1 (2%)                                             
      Cytoplasmic Alteration, Focal                                 1 (2%)       3 (6%)                                             
      Hematopoietic Cell Proliferation                              1 (2%)       1 (2%)                                             
      Hyperplasia, Focal                                                                      1 (2%)                                
      Hypertrophy, Focal                               1 (2%)       3 (6%)                    1 (2%)                                
   Adrenal Medulla                                    (50)         (48)         (50)         (49)                                   
      Hyperplasia                                                   1 (2%)       3 (6%)                                             
   Islets, Pancreatic                                 (50)         (49)         (49)         (49)                                   
      Hyperplasia                                                   1 (2%)       1 (2%)                                             
   Parathyroid Gland                                  (49)         (47)         (42)         (45)                                   
      Cyst                                             1 (2%)       1 (2%)       2 (5%)       2 (4%)                                
      Infiltration Cellular, Lymphocyte                1 (2%)                                                                       
   Pituitary Gland                                    (49)         (45)         (50)         (48)                                   
      Angiectasis                                      3 (6%)                                 1 (2%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    3                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hemorrhage                                                                              1 (2%)                                
      Pars Distalis, Angiectasis                       1 (2%)                                                                       
      Pars Distalis, Cyst                              1 (2%)       4 (9%)       1 (2%)                                             
      Pars Distalis, Cytoplasmic Alteration, Focal     3 (6%)       1 (2%)       2 (4%)       2 (4%)                                
      Pars Distalis, Hyperplasia, Focal                4 (8%)       7 (16%)     14 (28%)      6 (13%)                               
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Degeneration, Cystic, Focal                     12 (24%)     13 (26%)     10 (20%)     15 (30%)                               
      Inflammation, Chronic, Focal                     1 (2%)                                                                       
      Follicle, Cyst                                   2 (4%)      11 (22%)      5 (10%)      7 (14%)                               
      Follicular Cell, Hyperplasia                     7 (14%)      8 (16%)      8 (16%)     11 (22%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (49)         (49)         (49)                                   
      Degeneration, Cystic                             7 (14%)      3 (6%)       1 (2%)       6 (12%)                               
      Inflammation, Chronic                            1 (2%)                                 1 (2%)                                
   Ovary                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                                             1 (2%)                                
      Cyst                                             6 (12%)      5 (10%)      5 (10%)      9 (18%)                               
      Hemorrhage                                       1 (2%)       2 (4%)       5 (10%)      1 (2%)                                
      Inflammation, Suppurative                                                               2 (4%)                                
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)                                                                       
      Cyst                                             1 (2%)                    2 (4%)       1 (2%)                                
      Hemorrhage                                       2 (4%)       1 (2%)       1 (2%)                                             
      Hydrometra                                      20 (40%)     19 (38%)     18 (36%)     13 (26%)                               
      Inflammation, Chronic                                                      1 (2%)                                             
      Inflammation, Suppurative                                                               1 (2%)                                
      Endometrium, Hyperplasia, Cystic                48 (96%)     41 (82%)     43 (86%)     40 (80%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (49)         (50)                                   
      Depletion Cellular                                                                      1 (2%)                                
      Hyperplasia                                      4 (8%)       4 (8%)       4 (8%)       2 (4%)                                
      Myelofibrosis                                                 1 (2%)                                                          
      Necrosis                                                                   1 (2%)                                             
   Lymph Node                                         (6)          (8)          (7)          (6)                                    
      Hyperplasia                                                                1 (14%)                                            
      Iliac, Inflammation, Chronic                                               1 (14%)                                            
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    4                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Inguinal, Hyperplasia, Lymphoid                                                         1 (17%)                               
      Mediastinal, Hemorrhage                          1 (17%)                                                                      
   Lymph Node, Mandibular                             (48)         (49)         (44)         (43)                                   
      Ectasia                                                                    1 (2%)                                             
      Hemorrhage                                       2 (4%)       2 (4%)       1 (2%)                                             
      Hyperplasia, Lymphoid                            1 (2%)       3 (6%)       1 (2%)       1 (2%)                                
   Lymph Node, Mesenteric                             (48)         (46)         (48)         (45)                                   
      Atrophy                                                                                 1 (2%)                                
      Ectasia                                          1 (2%)                                                                       
      Hemorrhage                                       2 (4%)       1 (2%)       2 (4%)                                             
      Hyperplasia, Lymphoid                            1 (2%)                    1 (2%)       1 (2%)                                
      Inflammation, Chronic                                                      1 (2%)                                             
   Spleen                                             (50)         (50)         (49)         (48)                                   
      Congestion                                       1 (2%)                                                                       
      Depletion Cellular                                                                      2 (4%)                                
      Fibrosis, Focal                                                            1 (2%)       1 (2%)                                
      Hematopoietic Cell Proliferation                13 (26%)     21 (42%)     19 (39%)     12 (25%)                               
      Hyperplasia, Lymphoid                            5 (10%)      3 (6%)       2 (4%)       4 (8%)                                
      Infarct                                                       1 (2%)                                                          
      Necrosis, Focal                                                                         1 (2%)                                
   Thymus                                             (47)         (44)         (49)         (47)                                   
      Atrophy                                          2 (4%)       3 (7%)       2 (4%)       2 (4%)                                
      Cyst                                             1 (2%)       1 (2%)                    2 (4%)                                
      Hemorrhage                                                                              1 (2%)                                
      Hyperplasia, Lymphoid                            1 (2%)       1 (2%)                                                          
      Necrosis                                         1 (2%)                    1 (2%)       2 (4%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (49)         (49)         (50)         (49)                                   
      Ectasia                                          1 (2%)       1 (2%)       2 (4%)       1 (2%)                                
      Hyperplasia                                      1 (2%)                    3 (6%)       2 (4%)                                
   Skin                                               (49)         (50)         (50)         (50)                                   
      Inflammation, Chronic, Focal                     2 (4%)                    2 (4%)       2 (4%)                                
      Ulcer                                                                      2 (4%)                                             
      Dermis, Fibrosis                                              2 (4%)                    3 (6%)                                
      Epidermis, Hyperplasia, Focal                                              2 (4%)       1 (2%)                                
      Pinna, Ulcer                                                               1 (2%)                                             
      Subcutaneous Tissue, Edema                                    4 (8%)                    1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    5                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Fibrous Osteodystrophy                           9 (18%)      6 (12%)     11 (22%)     17 (34%)                               
      Hyperostosis                                                               1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Atrophy, Focal                                   3 (6%)       1 (2%)       2 (4%)       2 (4%)                                
      Hemorrhage                                       1 (2%)                                 1 (2%)                                
      Necrosis                                                                   2 (4%)                                             
   Spinal Cord                                        (2)          (1)          (1)          (1)                                    
      Hemorrhage, Focal                                1 (50%)                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
      Hyperplasia, Histiocytic                         2 (4%)                                                                       
      Pigmentation                                     1 (2%)                                                                       
      Thrombosis                                                                 1 (2%)                                             
      Alveolar Epithelium, Hyperplasia                              1 (2%)       2 (4%)                                             
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Suppurative                                                  1 (2%)                                             
      Mucosa, Glands, Dilatation, Focal                2 (4%)       2 (4%)                    1 (2%)                                
      Nasolacrimal Duct, Cyst                                                    1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (1)          (1)          (2)                                                 
      Atrophy                                          1 (100%)                                                                     
      Cornea, Inflammation, Chronic                                 1 (100%)     2 (100%)                                           
   Harderian Gland                                    (6)          (6)          (8)          (2)                                    
      Hyperplasia, Focal                                            1 (17%)                                                         
      Inflammation, Chronic, Focal                                               2 (25%)                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Congestion                                                                              1 (2%)                                
      Hyperplasia, Lymphoid                                         1 (2%)                                                          
      Infarct                                                                    1 (2%)                                             
      Metaplasia, Focal, Osseous                                    2 (4%)       3 (6%)                                             
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    6                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        VEHICLE      7.5          25 MG/KG     75 MG/KG                                  
                                                   CONTROL      MG/KG                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
      Nephropathy                                     25 (50%)     27 (54%)     27 (54%)     25 (50%)                               
      Thrombosis                                                                 1 (2%)                                             
      Pelvis, Dilatation                               1 (2%)                                                                       
      Renal Tubule, Accumulation, Hyaline Droplet                   3 (6%)                                                          
      Renal Tubule, Casts Protein                                                1 (2%)                                             
      Renal Tubule, Degeneration                       3 (6%)                    1 (2%)       4 (8%)                                
      Renal Tubule, Dilatation                                      1 (2%)       1 (2%)                                             
      Renal Tubule, Mineralization                     1 (2%)                                 1 (2%)                                
      Renal Tubule, Pigmentation                                                 1 (2%)       1 (2%)                                
   Urinary Bladder                                    (49)         (49)         (49)         (50)                                   
      Hyperplasia, Lymphoid                            2 (4%)       2 (4%)                    1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    7                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          VEHICLE      15 MG/KG     50 MG/KG     150                                       
                                                   CONTROL                                MG/KG                                     
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      5            6            4           15                                     
    Moribund Sacrifice                                 9            9            2            9                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                36           35           44           26                                     
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (49)         (49)         (48)         (43)                                   
      Inflammation, Chronic                                         1 (2%)                                                          
   Intestine Small, Duodenum                          (48)         (49)         (49)         (41)                                   
      Inflammation, Chronic, Focal                     1 (2%)                                                                       
      Necrosis, Focal                                                                         1 (2%)                                
   Intestine Small, Jejunum                           (48)         (47)         (47)         (41)                                   
      Peyer's Patch, Hyperplasia, Lymphoid                                       1 (2%)                                             
   Intestine Small, Ileum                             (48)         (48)         (47)         (38)                                   
      Peyer's Patch, Hyperplasia, Lymphoid                          1 (2%)       1 (2%)                                             
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                   2 (4%)                                                          
      Basophilic Focus                                              1 (2%)                    1 (2%)                                
      Clear Cell Focus                                 2 (4%)       2 (4%)       3 (6%)                                             
      Congestion                                                    1 (2%)                                                          
      Eosinophilic Focus                               6 (12%)      6 (12%)      9 (18%)                                            
      Hepatodiaphragmatic Nodule                                    1 (2%)                                                          
      Inflammation, Chronic                           24 (48%)     25 (50%)     16 (32%)      3 (6%)                                
      Mineralization, Focal                                                                   1 (2%)                                
      Mixed Cell Focus                                              1 (2%)                                                          
      Necrosis, Focal                                  5 (10%)      6 (12%)      3 (6%)       2 (4%)                                
      Vacuolization Cytoplasmic                       10 (20%)     11 (22%)      6 (12%)      1 (2%)                                
      Bile Duct, Cyst                                                            1 (2%)                                             
      Bile Duct, Hyperplasia                           1 (2%)       2 (4%)       2 (4%)                                             
      Hepatocyte, Hypertrophy                                                    1 (2%)       1 (2%)                                
      Hepatocyte, Karyomegaly                         15 (30%)     14 (28%)     12 (24%)      2 (4%)                                
   Mesentery                                          (10)         (4)          (2)                                                 
      Hemorrhage                                       2 (20%)                                                                      
      Inflammation, Chronic                            1 (10%)      1 (25%)                                                         
      Thrombosis                                       1 (10%)                                                                      
      Artery, Inflammation, Chronic                    3 (30%)      1 (25%)                                                         
      Artery, Thrombosis                               1 (10%)                                                                      
      Fat, Necrosis                                    2 (20%)      1 (25%)      1 (50%)                                            
   Pancreas                                           (50)         (49)         (49)         (50)                                   
      Inflammation, Chronic                                         1 (2%)                                                          
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    8                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          VEHICLE      15 MG/KG     50 MG/KG     150                                       
                                                   CONTROL                                MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Acinus, Atrophy, Diffuse                                      2 (4%)                                                          
      Acinus, Atrophy, Focal                           1 (2%)                    1 (2%)       1 (2%)                                
      Artery, Hypertrophy                              1 (2%)                                                                       
      Duct, Cyst                                       1 (2%)       2 (4%)                                                          
   Salivary Glands                                    (50)         (50)         (50)         (49)                                   
      Vacuolization Cytoplasmic                                                               1 (2%)                                
   Stomach, Forestomach                               (50)         (50)         (50)         (49)                                   
      Inflammation, Chronic                            1 (2%)       3 (6%)       1 (2%)                                             
      Ulcer                                            1 (2%)       3 (6%)                                                          
      Epithelium, Hyperplasia                         14 (28%)     12 (24%)     16 (32%)     13 (27%)                               
   Stomach, Glandular                                 (50)         (49)         (49)         (43)                                   
      Edema                                                                                   1 (2%)                                
      Erosion                                                                                 1 (2%)                                
      Hyperplasia                                                                1 (2%)                                             
      Mineralization                                   1 (2%)       4 (8%)       3 (6%)       1 (2%)                                
      Glands, Degeneration, Cystic, Focal              2 (4%)       7 (14%)      1 (2%)       2 (5%)                                
   Tooth                                              (10)         (5)                                                              
      Developmental Malformation                      10 (100%)     5 (100%)                                                        
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                    1 (2%)                                                          
      Inflammation, Chronic, Focal                     1 (2%)       1 (2%)                                                          
      Mineralization                                                                          1 (2%)                                
      Thrombosis                                       2 (4%)       1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (49)                                   
      Accessory Adrenal Cortical Nodule                1 (2%)       1 (2%)                                                          
      Cyst                                             1 (2%)                                                                       
      Cytoplasmic Alteration, Focal                    1 (2%)       1 (2%)       2 (4%)                                             
      Hyperplasia, Focal                                            1 (2%)       2 (4%)                                             
      Hypertrophy, Focal                               6 (12%)      7 (14%)      9 (18%)      7 (14%)                               
      Capsule, Hyperplasia, Focal                                   2 (4%)                    2 (4%)                                
   Adrenal Medulla                                    (49)         (50)         (49)         (49)                                   
      Hyperplasia                                      1 (2%)                    1 (2%)                                             
   Islets, Pancreatic                                 (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      4 (8%)       2 (4%)                                                          
   Parathyroid Gland                                  (48)         (49)         (49)         (46)                                   
      Cyst                                             1 (2%)       1 (2%)       2 (4%)                                             
   Pituitary Gland                                    (49)         (50)         (48)         (44)                                   
      Angiectasis                                      1 (2%)       1 (2%)                                                          
      Pars Distalis, Cyst                              2 (4%)       2 (4%)       3 (6%)       1 (2%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    9                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          VEHICLE      15 MG/KG     50 MG/KG     150                                       
                                                   CONTROL                                MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Pars Distalis, Cytoplasmic Alteration, Focal     2 (4%)                                                                       
      Pars Distalis, Hyperplasia, Focal                1 (2%)       3 (6%)       2 (4%)       2 (5%)                                
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Degeneration, Cystic, Focal                      6 (12%)     11 (22%)     10 (20%)     13 (26%)                               
      Follicle, Cyst                                   1 (2%)       6 (12%)      3 (6%)       2 (4%)                                
      Follicular Cell, Hyperplasia                     3 (6%)       1 (2%)       3 (6%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (49)         (50)         (50)         (50)                                   
      Granuloma Sperm                                  1 (2%)       2 (4%)                                                          
      Inflammation, Chronic                            1 (2%)                                                                       
      Spermatocele                                     1 (2%)                                                                       
   Penis                                              (1)                                                                           
      Angiectasis                                      1 (100%)                                                                     
   Preputial Gland                                    (49)         (48)         (50)         (50)                                   
      Degeneration, Cystic                            23 (47%)     31 (65%)     31 (62%)     12 (24%)                               
      Inflammation, Chronic                           10 (20%)      8 (17%)      1 (2%)       3 (6%)                                
      Inflammation, Suppurative                                                  1 (2%)       1 (2%)                                
   Prostate                                           (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                                         1 (2%)                    1 (2%)                                
      Epithelium, Hyperplasia, Focal                   1 (2%)                                                                       
   Seminal Vesicle                                    (50)         (50)         (50)         (50)                                   
      Cyst                                             1 (2%)                                                                       
      Inflammation, Chronic                                         2 (4%)                                                          
   Testes                                             (50)         (50)         (50)         (50)                                   
      Cyst                                             1 (2%)                                                                       
      Mineralization, Focal                            1 (2%)                                 1 (2%)                                
      Germinal Epithelium, Degeneration                1 (2%)                                 1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (49)                                   
      Angiectasis                                      1 (2%)                                                                       
      Depletion Cellular                                                                      1 (2%)                                
      Hyperplasia                                      5 (10%)      2 (4%)                                                          
   Lymph Node                                         (5)          (6)          (5)          (3)                                    
      Bronchial, Hyperplasia, Lymphoid                                                        1 (33%)                               
      Inguinal, Hyperplasia, Lymphoid                  1 (20%)      2 (33%)                   1 (33%)                               
      Inguinal, Pigmentation                                                                  1 (33%)                               
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   10                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          VEHICLE      15 MG/KG     50 MG/KG     150                                       
                                                   CONTROL                                MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Mediastinal, Hemorrhage                          1 (20%)                                                                      
      Pancreatic, Hyperplasia, Lymphoid                             2 (33%)                                                         
      Renal, Hyperplasia                                            1 (17%)                                                         
   Lymph Node, Mandibular                             (42)         (47)         (47)         (47)                                   
      Hyperplasia, Histiocytic                         1 (2%)                                                                       
      Hyperplasia, Lymphoid                                                      1 (2%)       2 (4%)                                
      Necrosis                                                                                1 (2%)                                
   Lymph Node, Mesenteric                             (50)         (46)         (50)         (48)                                   
      Atrophy                                                                                 2 (4%)                                
      Ectasia                                          3 (6%)                    1 (2%)                                             
      Hematopoietic Cell Proliferation                 1 (2%)                                                                       
      Hemorrhage                                      17 (34%)     13 (28%)      9 (18%)      6 (13%)                               
      Hyperplasia, Lymphoid                            1 (2%)                    3 (6%)       2 (4%)                                
      Pigmentation                                                  1 (2%)                                                          
   Spleen                                             (50)         (49)         (50)         (49)                                   
      Depletion Cellular                               1 (2%)                                12 (24%)                               
      Fibrosis, Focal                                  1 (2%)                                                                       
      Hematopoietic Cell Proliferation                20 (40%)     27 (55%)     25 (50%)     13 (27%)                               
      Hyperplasia, Lymphoid                                                      1 (2%)                                             
   Thymus                                             (43)         (42)         (44)         (46)                                   
      Atrophy                                          2 (5%)       6 (14%)      4 (9%)       5 (11%)                               
      Cyst                                             6 (14%)      6 (14%)      5 (11%)      3 (7%)                                
      Necrosis                                                      1 (2%)       1 (2%)      11 (24%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic, Focal                                                            1 (2%)                                
      Dermis, Fibrosis                                              1 (2%)                                                          
      Epidermis, Hyperplasia, Focal                                              1 (2%)                                             
      Subcutaneous Tissue, Edema                       1 (2%)       2 (4%)       1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Cranium, Hyperostosis                                         1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       1 (2%)                                                                       
      Necrosis                                         1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   11                                                              
NTP Experiment-Test: 05067-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                            THEOPHYLLINE                                       Date: 07/03/96  
Route: GAVAGE                                                                                                     Time: 13:10:54  
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          VEHICLE      15 MG/KG     50 MG/KG     150                                       
                                                   CONTROL                                MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                                    1 (2%)                    4 (8%)                                
      Foreign Body                                                  1 (2%)                                                          
      Hemorrhage                                       3 (6%)       1 (2%)                    1 (2%)                                
      Hyperplasia, Histiocytic                         4 (8%)                    4 (8%)       1 (2%)                                
      Alveolar Epithelium, Hyperplasia                 1 (2%)       2 (4%)       1 (2%)                                             
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Suppurative                        1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Harderian Gland                                    (1)          (4)          (2)          (2)                                    
      Inflammation, Chronic, Focal                                  1 (25%)                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (49)         (50)         (50)                                   
      Congestion                                       1 (2%)                                 1 (2%)                                
      Cyst                                             2 (4%)                    1 (2%)       2 (4%)                                
      Infarct                                                                    2 (4%)       2 (4%)                                
      Inflammation, Chronic                            1 (2%)                                                                       
      Inflammation, Suppurative                        1 (2%)       1 (2%)       1 (2%)                                             
      Metaplasia, Focal, Osseous                                    1 (2%)       2 (4%)       1 (2%)                                
      Nephropathy                                     46 (92%)     46 (94%)     45 (90%)     29 (58%)                               
      Papilla, Necrosis                                                          1 (2%)                                             
      Renal Tubule, Degeneration                                                              7 (14%)                               
      Renal Tubule, Dilatation                                                                4 (8%)                                
   Urethra                                            (3)          (3)          (1)                                                 
      Inflammation, Chronic                                         1 (33%)                                                         
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   12                                                              
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                             ----------              END OF REPORT             ----------                                           
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NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.