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TDMS Study 05068-10 Pathology Tables

NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96
Route: DOSED FEED                                                                                                 Time: 23:43:31




       Facility:  Microbiological Associates

       Chemical CAS #:  76-57-3

       Lock Date:  03/03/92

       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: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________

DISPOSITION SUMMARY                                                                                                                 

  Animals Initially In Study                          60           60           60           60                                     

  Scheduled Sacrifice                                 10            9            9            9                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 7            9            6            4                                     
    Natural Death                                      7            6            2           11                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                35           36           43           34                                     
    Natural Death                                      1                                      1                                     
  Missing                                                                                     1                                     

  Animals Examined Microscopically                    60           60           60           59                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Gallbladder                                        (53)         (50)         (56)         (50)                                   
      Inflammation, Chronic Active                     1 (2%)                                 1 (2%)                                
   Intestine Small, Duodenum                          (58)         (58)         (57)         (57)                                   
      Ulcer                                                                      1 (2%)                                             
   Intestine Small, Jejunum                           (60)         (57)         (59)         (59)                                   
      Hemorrhage                                                                              1 (2%)                                
      Hyperplasia, Lymphoid                                         1 (2%)       1 (2%)       1 (2%)                                
   Liver                                              (60)         (60)         (60)         (59)                                   
      Angiectasis                                      1 (2%)                                 1 (2%)                                
      Atrophy                                                                    1 (2%)                                             
      Basophilic Focus                                 1 (2%)                    1 (2%)       1 (2%)                                
      Clear Cell Focus                                                           1 (2%)                                             
      Congestion                                                                              1 (2%)                                
      Cyst                                                          1 (2%)       2 (3%)                                             
      Eosinophilic Focus                               6 (10%)      7 (12%)      9 (15%)      2 (3%)                                
      Fatty Change, Focal                                                        1 (2%)                                             
      Hematopoietic Cell Proliferation                 3 (5%)       5 (8%)                    3 (5%)                                
      Infarct                                                                    2 (3%)       1 (2%)                                
      Inflammation, Chronic Active                    11 (18%)     10 (17%)     14 (23%)      6 (10%)                               
      Mineralization                                                             1 (2%)                                             
      Mitotic Alteration                                            1 (2%)                    1 (2%)                                
      Mixed Cell Focus                                                           3 (5%)       1 (2%)                                
      Necrosis                                         2 (3%)       2 (3%)       2 (3%)       2 (3%)                                
      Bile Duct, Hyperplasia                                                     1 (2%)                                             
      Centrilobular, Inflammation, Chronic                                       1 (2%)                                             
      Centrilobular, Necrosis                          1 (2%)                                                                       
      Centrilobular, Pigmentation                                                1 (2%)                                             
      Hepatocyte, Necrosis                                          1 (2%)                                                          
      Kupffer Cell, Hypertrophy                                                               1 (2%)                                
   Mesentery                                          (10)         (9)          (7)          (5)                                    

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

                                                             Page    2                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation, Chronic Active                     2 (20%)                                1 (20%)                               
      Artery, Inflammation, Chronic Active                                       1 (14%)                                            
      Fat, Necrosis                                    6 (60%)      8 (89%)      6 (86%)      2 (40%)                               
   Pancreas                                           (60)         (60)         (60)         (59)                                   
      Inflammation, Chronic                            5 (8%)       4 (7%)       4 (7%)                                             
      Inflammation, Chronic Active                     2 (3%)                    1 (2%)       2 (3%)                                
      Acinar Cell, Atrophy                             2 (3%)       1 (2%)       1 (2%)       2 (3%)                                
      Acinar Cell, Depletion Secretory                 1 (2%)                                                                       
      Duct, Cyst                                       1 (2%)       1 (2%)                    2 (3%)                                
   Salivary Glands                                    (60)         (59)         (60)         (59)                                   
      Inflammation, Chronic                           34 (57%)     34 (58%)     34 (57%)     27 (46%)                               
   Stomach, Forestomach                               (60)         (60)         (60)         (59)                                   
      Hyperplasia                                      1 (2%)       1 (2%)       2 (3%)       1 (2%)                                
      Inflammation, Acute                                                                     1 (2%)                                
      Inflammation, Chronic Active                     2 (3%)                    2 (3%)       3 (5%)                                
   Stomach, Glandular                                 (60)         (60)         (60)         (58)                                   
      Cyst                                                                                    1 (2%)                                
      Dilatation                                       1 (2%)                                                                       
      Dysplasia                                        1 (2%)                                                                       
      Inflammation, Chronic Active                     3 (5%)      10 (17%)                   6 (10%)                               
      Necrosis                                         2 (3%)       1 (2%)       1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Blood Vessel                                       (60)         (60)         (59)         (58)                                   
      Aorta, Inflammation, Chronic Active                                        1 (2%)                                             
   Heart                                              (60)         (60)         (60)         (59)                                   
      Fibrosis                                                      2 (3%)                                                          
      Inflammation, Chronic Active                     2 (3%)                                                                       
      Mineralization                                                1 (2%)                                                          
      Thrombosis                                                    2 (3%)                                                          
      Artery, Inflammation, Chronic Active                          1 (2%)       1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (60)         (60)         (59)         (59)                                   
      Angiectasis                                                   1 (2%)                    1 (2%)                                
      Cyst                                                                       1 (2%)                                             
      Cytoplasmic Alteration, Focal                    1 (2%)                                                                       
      Hematopoietic Cell Proliferation                              2 (3%)                                                          
      Hypertrophy, Focal                                                         1 (2%)                                             
      Inflammation, Chronic Active                                                            3 (5%)                                
      Subcapsular, Hyperplasia                        57 (95%)     55 (92%)     58 (98%)     54 (92%)                               
   Adrenal Medulla                                    (59)         (59)         (59)         (57)                                   
      Hyperplasia                                                   1 (2%)       2 (3%)       2 (4%)                                

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

                                                             Page    3                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
   Pituitary Gland                                    (58)         (56)         (58)         (55)                                   
      Craniopharyngeal Duct, Hyperplasia                                         1 (2%)                                             
      Pars Distalis, Angiectasis                       2 (3%)       1 (2%)                    2 (4%)                                
      Pars Distalis, Cyst                                           1 (2%)                    2 (4%)                                
      Pars Distalis, Hyperplasia                      12 (21%)     12 (21%)     13 (22%)     11 (20%)                               
      Pars Intermedia, Hyperplasia                     1 (2%)                                 1 (2%)                                
   Thyroid Gland                                      (58)         (60)         (60)         (59)                                   
      Inflammation, Chronic Active                     2 (3%)       6 (10%)     10 (17%)      4 (7%)                                
      Follicle, Cyst                                   3 (5%)       1 (2%)       5 (8%)       3 (5%)                                
      Follicular Cell, Hyperplasia, Diffuse                                      1 (2%)                                             
      Follicular Cell, Hyperplasia, Focal             14 (24%)     29 (48%)     43 (72%)     45 (76%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (51)         (51)         (53)         (52)                                   
      Dilatation                                      42 (82%)     46 (90%)     47 (89%)     47 (90%)                               
      Inflammation, Chronic Active                     3 (6%)       4 (8%)       5 (9%)      10 (19%)                               
      Pigmentation                                     3 (6%)       2 (4%)       2 (4%)       1 (2%)                                
   Ovary                                              (58)         (60)         (59)         (59)                                   
      Abscess                                          1 (2%)                                 3 (5%)                                
      Cyst                                             6 (10%)     12 (20%)     14 (24%)      7 (12%)                               
      Hemorrhage                                                                 1 (2%)                                             
      Infiltration Cellular, Histiocyte                                          2 (3%)                                             
      Inflammation, Chronic Active                     2 (3%)                                 2 (3%)                                
      Periovarian Tissue, Infiltration Cellular,                                                                                    
           Lymphocyte                                                            1 (2%)       1 (2%)                                
   Oviduct                                            (3)          (1)                       (1)                                    
      Cyst                                             1 (33%)                                                                      
      Dilatation                                                    1 (100%)                                                        
      Inflammation, Chronic Active                     1 (33%)      1 (100%)                                                        
   Uterus                                             (60)         (60)         (59)         (59)                                   
      Atrophy                                                                    1 (2%)                                             
      Dilatation                                      12 (20%)     14 (23%)     10 (17%)      9 (15%)                               
      Hemorrhage                                                    2 (3%)                                                          
      Hyperplasia, Cystic                             46 (77%)     49 (82%)     46 (78%)     46 (78%)                               
      Inflammation, Chronic Active                                  1 (2%)                                                          
      Cervix, Inflammation, Chronic Active                                       1 (2%)                                             
      Lymphatic, Ectasia                                            1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    

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

                                                             Page    4                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (60)         (60)         (60)         (59)                                   
      Atrophy                                                       1 (2%)                                                          
      Congestion                                                    1 (2%)       1 (2%)                                             
      Myeloid Cell, Hyperplasia                        4 (7%)       2 (3%)       1 (2%)       1 (2%)                                
   Lymph Node                                         (4)          (2)          (2)          (9)                                    
      Iliac, Hyperplasia, Lymphoid                                               1 (50%)                                            
      Iliac, Inflammation, Chronic Active              1 (25%)                                                                      
      Inguinal, Pigmentation                                                     1 (50%)                                            
      Mediastinal, Hyperplasia, Plasma Cell                                                   1 (11%)                               
   Lymph Node, Mandibular                             (54)         (55)         (58)         (56)                                   
      Hemorrhage                                       2 (4%)       1 (2%)                                                          
      Hyperplasia, Lymphoid                                         1 (2%)       4 (7%)       4 (7%)                                
   Lymph Node, Mesenteric                             (59)         (57)         (56)         (57)                                   
      Cyst                                                          2 (4%)                                                          
      Fibrosis                                                      1 (2%)                                                          
      Hematopoietic Cell Proliferation                 1 (2%)       1 (2%)       2 (4%)                                             
      Hemorrhage                                       4 (7%)       2 (4%)       1 (2%)                                             
      Hyperplasia, Lymphoid                            1 (2%)                                                                       
      Infiltration Cellular, Histiocyte                                          1 (2%)                                             
      Inflammation, Chronic Active                                                            1 (2%)                                
   Spleen                                             (60)         (60)         (60)         (58)                                   
      Atrophy                                                                    1 (2%)                                             
      Fibrosis                                                      1 (2%)       1 (2%)                                             
      Hematopoietic Cell Proliferation                17 (28%)     19 (32%)     18 (30%)     14 (24%)                               
      Hyperplasia, Lymphoid                            1 (2%)       4 (7%)       6 (10%)      3 (5%)                                
      Infiltration Cellular, Plasma Cell                            1 (2%)                                                          
      Pigmentation, Hemosiderin                        1 (2%)                    2 (3%)       1 (2%)                                
      Capsule, Inflammation, Chronic Active            1 (2%)                                 1 (2%)                                
   Thymus                                             (48)         (50)         (56)         (51)                                   
      Atrophy                                          5 (10%)      9 (18%)      4 (7%)       6 (12%)                               
      Ectopic Parathyroid Gland                                     1 (2%)                    1 (2%)                                
      Ectopic Thyroid                                                            1 (2%)                                             
      Hyperplasia, Lymphoid                            2 (4%)       7 (14%)      8 (14%)      5 (10%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (55)         (60)         (59)         (59)                                   
      Hyperplasia                                                                2 (3%)                                             
      Infiltration Cellular, Lymphocyte                             1 (2%)                                                          
      Inflammation, Chronic Active                     1 (2%)                                 1 (2%)                                
   Skin                                               (60)         (60)         (60)         (59)                                   
      Developmental Malformation                       1 (2%)                                                                       
      Inflammation, Chronic Active                     5 (8%)       3 (5%)       7 (12%)      5 (8%)                                
      Ulcer                                            1 (2%)                                                                       
      Epidermis, Hyperplasia                           1 (2%)       1 (2%)       1 (2%)       1 (2%)                                

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

                                                             Page    5                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
INTEGUMENTARY SYSTEM - CONT                                                                                                         
      Subcutaneous Tissue, Abscess                     1 (2%)                                                                       
      Subcutaneous Tissue, Inflammation, Chronic                                                                                    
          Active                                       1 (2%)                                 1 (2%)                                
      Subcutaneous Tissue, Pigmentation                1 (2%)                                                                       
      Subcutaneous Tissue, Fat, Atrophy                1 (2%)                    1 (2%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (60)         (60)         (60)         (59)                                   
      Dysplasia                                       12 (20%)      6 (10%)      8 (13%)      6 (10%)                               
      Fracture                                                                   1 (2%)                                             
      Artery, Inflammation, Chronic Active                                       1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (60)         (60)         (60)         (59)                                   
      Compression                                      3 (5%)       1 (2%)       3 (5%)       1 (2%)                                
      Degeneration                                                  1 (2%)                                                          
      Hemorrhage                                       1 (2%)                                                                       
      Infiltration Cellular, Histiocyte                                          1 (2%)                                             
      Mineralization                                  27 (45%)     21 (35%)     22 (37%)     12 (20%)                               
      Artery, Inflammation, Chronic Active                                       1 (2%)                                             
      Meninges, Inflammation, Chronic                  1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (60)         (60)         (60)         (59)                                   
      Congestion                                                    1 (2%)                                                          
      Hemorrhage                                                    1 (2%)                                                          
      Infiltration Cellular, Lymphocyte               38 (63%)     28 (47%)     33 (55%)     24 (41%)                               
      Infiltration Cellular, Histiocyte                1 (2%)                                                                       
      Pigmentation, Hemosiderin                        1 (2%)                                                                       
      Alveolar Epithelium, Hyperplasia                 1 (2%)       1 (2%)       2 (3%)       1 (2%)                                
   Nose                                               (60)         (60)         (59)         (59)                                   
      Olfactory Epithelium, Degeneration, Hyaline     36 (60%)     39 (65%)     35 (59%)     50 (85%)                               
      Respiratory Epithelium, Degeneration, Hyaline    7 (12%)      6 (10%)      8 (14%)      8 (14%)                               
      Respiratory Epithelium, Hyperplasia,                                                                                          
          Glandular                                    2 (3%)                                                                       
      Respiratory Epithelium, Inflammation,                                                                                         
          Chronic Active                               1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    

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

                                                             Page    6                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE FEMALE                        0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                             (1)          (2)          (3)                                    
      Atrophy                                                                    1 (50%)                                            
      Inflammation, Chronic Active                                               1 (50%)      2 (67%)                               
      Cornea, Inflammation, Chronic Active                                                    1 (33%)                               
   Harderian Gland                                    (2)          (4)          (3)          (3)                                    
      Hyperplasia, Focal                               1 (50%)                                                                      
      Inflammation, Chronic Active                                               2 (67%)      1 (33%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (60)         (60)         (60)         (59)                                   
      Amyloid Deposition                               1 (2%)                                                                       
      Atrophy                                                                                 1 (2%)                                
      Cyst                                                          1 (2%)                                                          
      Glomerulosclerosis                               1 (2%)                                                                       
      Hemorrhage                                                                              1 (2%)                                
      Hydronephrosis                                                                          1 (2%)                                
      Infarct                                          1 (2%)                    2 (3%)       2 (3%)                                
      Inflammation, Chronic                           14 (23%)     19 (32%)     15 (25%)     18 (31%)                               
      Metaplasia, Osseous                              1 (2%)                                                                       
      Nephropathy                                                   3 (5%)       2 (3%)       1 (2%)                                
      Capsule, Inflammation, Chronic Active                                                   1 (2%)                                
      Glomerulus, Inflammation, Chronic                                                       1 (2%)                                
      Perirenal Tissue, Inflammation, Chronic                                                                                       
          Active                                                                              1 (2%)                                
      Renal Tubule, Degeneration, Hyaline              1 (2%)                                 1 (2%)                                
      Renal Tubule, Karyomegaly                                                  1 (2%)                                             
      Renal Tubule, Pigmentation                                                              1 (2%)                                
      Renal Tubule, Regeneration                      21 (35%)     28 (47%)     31 (52%)     19 (32%)                               
   Ureter                                                                       (1)                                                 
      Infiltration Cellular, Lymphocyte                                          1 (100%)                                           
   Urinary Bladder                                    (60)         (59)         (60)         (59)                                   
      Dilatation                                       1 (2%)                                                                       
      Infiltration Cellular, Lymphocyte               38 (63%)     45 (76%)     46 (77%)     42 (71%)                               
      Inflammation, Chronic Active                                                            1 (2%)                                
      Artery, Inflammation, Chronic Active                                       1 (2%)                                             
                                                                                                                                    

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

                                                             Page    7                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________

DISPOSITION SUMMARY                                                                                                                 

  Animals Initially In Study                          60           60           60           60                                     

  Scheduled Sacrifice                                 10           10           10           10                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 4            4            2            1                                     
    Natural Death                                      5            7            3            6                                     
    Accidently Killed                                               1                                                               
  Survivors                                                                                                                         
    Terminal Sacrifice                                41           38           45           43                                     

  Animals Examined Microscopically                    60           60           60           60                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Gallbladder                                        (44)         (50)         (50)         (50)                                   
      Degeneration, Hyaline                                         1 (2%)                                                          
      Dilatation                                                    1 (2%)                                                          
      Inflammation, Chronic                                         1 (2%)                                                          
      Inflammation, Chronic Active                     1 (2%)                                                                       
   Intestine Large, Cecum                             (60)         (60)         (60)         (58)                                   
      Hyperplasia, Lymphoid                            2 (3%)                                                                       
   Intestine Small, Jejunum                           (60)         (60)         (59)         (58)                                   
      Hyperplasia, Lymphoid                                                      1 (2%)       1 (2%)                                
   Intestine Small, Ileum                             (59)         (60)         (59)         (57)                                   
      Hyperplasia, Lymphoid                                                      1 (2%)                                             
      Hyperplasia, Plasma Cell                                      1 (2%)                                                          
      Inflammation, Chronic Active                                               1 (2%)                                             
   Liver                                              (60)         (60)         (60)         (60)                                   
      Basophilic Focus                                 4 (7%)       4 (7%)       2 (3%)       3 (5%)                                
      Clear Cell Focus                                 7 (12%)      4 (7%)       2 (3%)                                             
      Cyst                                                          1 (2%)                    1 (2%)                                
      Eosinophilic Focus                               9 (15%)     12 (20%)      5 (8%)       4 (7%)                                
      Fatty Change, Focal                              4 (7%)       4 (7%)                                                          
      Hematopoietic Cell Proliferation                 2 (3%)                                                                       
      Infarct                                                       3 (5%)       1 (2%)       2 (3%)                                
      Inflammation, Chronic Active                     2 (3%)       4 (7%)       3 (5%)       4 (7%)                                
      Mitotic Alteration                               1 (2%)       1 (2%)                                                          
      Mixed Cell Focus                                 1 (2%)       1 (2%)       3 (5%)                                             
      Necrosis                                         2 (3%)       3 (5%)                                                          
      Pigmentation                                                  1 (2%)       1 (2%)                                             
      Centrilobular, Cytomegaly                        3 (5%)                    1 (2%)                                             
      Centrilobular, Fatty Change                     13 (22%)     18 (30%)      6 (10%)      1 (2%)                                
   Mesentery                                          (1)          (3)          (3)          (2)                                    
      Hemorrhage                                                                 1 (33%)                                            
      Artery, Inflammation, Chronic Active                                       1 (33%)                                            

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

                                                             Page    8                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Fat, Necrosis                                                 3 (100%)     2 (67%)      1 (50%)                               
   Pancreas                                           (59)         (60)         (60)         (60)                                   
      Inflammation, Chronic                            2 (3%)                    1 (2%)       1 (2%)                                
      Acinar Cell, Atrophy                             2 (3%)       2 (3%)       1 (2%)                                             
      Acinar Cell, Vacuolization Cytoplasmic                                     1 (2%)                                             
      Artery, Inflammation, Chronic Active                          1 (2%)                                                          
      Duct, Cyst                                                    1 (2%)                                                          
   Salivary Glands                                    (60)         (60)         (60)         (60)                                   
      Inflammation, Chronic                           27 (45%)     27 (45%)     17 (28%)     14 (23%)                               
   Stomach, Forestomach                               (60)         (60)         (60)         (60)                                   
      Hyperplasia                                                   1 (2%)       2 (3%)                                             
      Inflammation, Chronic Active                                  1 (2%)                                                          
      Necrosis                                                                   1 (2%)                                             
   Stomach, Glandular                                 (59)         (60)         (60)         (59)                                   
      Developmental Malformation                                                 1 (2%)                                             
      Dilatation                                                    1 (2%)                                                          
      Inflammation, Chronic Active                     2 (3%)       3 (5%)                    1 (2%)                                
      Necrosis                                                      1 (2%)       1 (2%)                                             
   Tooth                                              (9)          (9)          (7)          (2)                                    
      Developmental Malformation                       9 (100%)     9 (100%)     7 (100%)     2 (100%)                              
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (60)         (60)         (60)         (60)                                   
      Fibrosis                                                                   2 (3%)       1 (2%)                                
      Artery, Inflammation, Chronic Active                                       1 (2%)       2 (3%)                                
      Atrium, Thrombosis                                                         2 (3%)                                             
      Ventricle, Thrombosis                                                      1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (59)         (58)         (60)         (60)                                   
      Hypertrophy, Focal                              23 (39%)     26 (45%)     22 (37%)     24 (40%)                               
      Extra Adrenal Tissue, Inflammation, Chronic                                                                                   
          Active                                       1 (2%)                                                                       
      Subcapsular, Hyperplasia                        38 (64%)     30 (52%)     29 (48%)     31 (52%)                               
   Islets, Pancreatic                                 (60)         (60)         (60)         (60)                                   
      Hyperplasia                                     10 (17%)     13 (22%)      6 (10%)      1 (2%)                                
   Pituitary Gland                                    (56)         (59)         (58)         (55)                                   
      Pars Distalis, Cyst                              1 (2%)       2 (3%)       2 (3%)       1 (2%)                                
      Pars Distalis, Hyperplasia                       4 (7%)       2 (3%)                                                          
   Thyroid Gland                                      (59)         (60)         (60)         (60)                                   
      Inflammation, Chronic Active                                  1 (2%)                                                          
      C-Cell, Hyperplasia, Focal                                                 1 (2%)                                             
      Follicle, Cyst                                                1 (2%)       1 (2%)                                             

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

                                                             Page    9                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Follicular Cell, Hyperplasia, Focal              7 (12%)     25 (42%)     29 (48%)     40 (67%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (60)         (60)         (60)         (60)                                   
      Granuloma Sperm                                  1 (2%)                                 1 (2%)                                
      Inflammation, Chronic Active                     5 (8%)       4 (7%)       5 (8%)                                             
      Spermatocele                                                               1 (2%)                                             
   Preputial Gland                                    (58)         (60)         (60)         (60)                                   
      Abscess                                          1 (2%)       1 (2%)                    1 (2%)                                
      Dilatation                                      49 (84%)     43 (72%)     45 (75%)     46 (77%)                               
      Hyperplasia                                                                             1 (2%)                                
      Inflammation, Chronic                            8 (14%)      6 (10%)      4 (7%)       5 (8%)                                
      Inflammation, Chronic Active                    23 (40%)     20 (33%)     23 (38%)     14 (23%)                               
   Prostate                                           (56)         (59)         (58)         (60)                                   
      Hyperplasia                                                                             1 (2%)                                
      Inflammation, Acute                                                                     1 (2%)                                
      Inflammation, Chronic                           12 (21%)     14 (24%)     15 (26%)     11 (18%)                               
      Inflammation, Chronic Active                     1 (2%)                    2 (3%)                                             
   Seminal Vesicle                                    (60)         (60)         (60)         (59)                                   
      Atrophy                                                                    1 (2%)                                             
      Dilatation                                      10 (17%)      7 (12%)      6 (10%)      1 (2%)                                
      Inflammation, Chronic Active                                               1 (2%)                                             
   Testes                                             (60)         (60)         (60)         (60)                                   
      Seminiferous Tubule, Degeneration                                          3 (5%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (60)         (60)         (60)         (60)                                   
      Congestion                                                    1 (2%)                    1 (2%)                                
      Myeloid Cell, Hyperplasia                        1 (2%)                    1 (2%)                                             
   Lymph Node                                         (6)          (1)                       (2)                                    
      Hemorrhage                                                                              1 (50%)                               
      Pancreatic, Hyperplasia, Lymphoid                                                       1 (50%)                               
   Lymph Node, Mandibular                             (48)         (53)         (56)         (55)                                   
      Hyperplasia, Lymphoid                                                      3 (5%)                                             
      Pigmentation, Hemosiderin                                                  1 (2%)       2 (4%)                                
   Lymph Node, Mesenteric                             (59)         (59)         (58)         (58)                                   
      Angiectasis                                                                             1 (2%)                                
      Granuloma                                                     1 (2%)                                                          

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

                                                             Page   10                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Hematopoietic Cell Proliferation                 5 (8%)       3 (5%)       1 (2%)       1 (2%)                                
      Hemorrhage                                      13 (22%)      9 (15%)      9 (16%)     10 (17%)                               
      Hyperplasia, Histiocytic                                      1 (2%)                                                          
      Hyperplasia, Lymphoid                            1 (2%)       2 (3%)       2 (3%)                                             
   Spleen                                             (60)         (60)         (58)         (60)                                   
      Hematopoietic Cell Proliferation                14 (23%)     13 (22%)     15 (26%)     10 (17%)                               
      Hyperplasia, Lymphoid                                                      2 (3%)                                             
      Hyperplasia, Reticulum Cell                                   1 (2%)                                                          
      Inflammation, Chronic Active                     1 (2%)                                                                       
   Thymus                                             (53)         (44)         (52)         (54)                                   
      Atrophy                                          5 (9%)       2 (5%)       7 (13%)      3 (6%)                                
      Cyst                                                          1 (2%)                                                          
      Ectopic Parathyroid Gland                                                  3 (6%)                                             
      Hyperplasia, Lymphoid                            1 (2%)       2 (5%)                                                          
      Necrosis                                                      1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (60)         (60)         (60)         (60)                                   
      Foreign Body                                     1 (2%)                                                                       
      Inflammation, Chronic Active                     2 (3%)       3 (5%)       4 (7%)       2 (3%)                                
      Ulcer                                                                      1 (2%)                                             
      Epidermis, Hyperplasia                           1 (2%)       2 (3%)       1 (2%)       5 (8%)                                
      Prepuce, Inflammation, Chronic Active                                                   1 (2%)                                
      Subcutaneous Tissue, Abscess                                  1 (2%)                                                          
      Subcutaneous Tissue, Edema                                    1 (2%)                                                          
      Subcutaneous Tissue, Inflammation, Chronic                                                                                    
          Active                                                                 1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Skeletal Muscle                                                 (1)                                                              
      Inflammation, Chronic                                         1 (100%)                                                        
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (60)         (59)         (60)         (60)                                   
      Compression                                      1 (2%)                                                                       
      Cyst                                                                       1 (2%)                                             
      Mineralization                                  40 (67%)     25 (42%)     15 (25%)     19 (32%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    

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

                                                             Page   11                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (60)         (60)         (60)         (60)                                   
      Congestion                                       1 (2%)                                 1 (2%)                                
      Infiltration Cellular, Lymphocyte               13 (22%)     19 (32%)     15 (25%)     10 (17%)                               
      Infiltration Cellular, Histiocyte                2 (3%)                    2 (3%)                                             
      Inflammation, Chronic Active                     1 (2%)       2 (3%)       1 (2%)                                             
      Alveolar Epithelium, Hyperplasia                 6 (10%)      5 (8%)       6 (10%)      2 (3%)                                
      Artery, Inflammation, Chronic Active                                       1 (2%)                                             
      Bronchiole, Hyperplasia                          1 (2%)                                                                       
      Interstitium, Inflammation, Chronic Active       2 (3%)       2 (3%)                    1 (2%)                                
      Pleura, Inflammation, Chronic                                              1 (2%)                                             
   Nose                                               (60)         (60)         (59)         (60)                                   
      Exudate                                          1 (2%)                                 1 (2%)                                
      Foreign Body                                                                            1 (2%)                                
      Olfactory Epithelium, Degeneration, Hyaline     25 (42%)     32 (53%)     30 (51%)     29 (48%)                               
      Respiratory Epithelium, Degeneration, Hyaline    1 (2%)       2 (3%)       4 (7%)       1 (2%)                                
      Respiratory Epithelium, Hyperplasia,                                                                                          
          Glandular                                    2 (3%)                    1 (2%)       1 (2%)                                
      Respiratory Epithelium, Inflammation,                                                                                         
          Chronic Active                               2 (3%)                                                                       
      Respiratory Epithelium, Metaplasia               1 (2%)                                                                       
      Respiratory Epithelium, Proliferation                                                                                         
          Connective Tissue                                         1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (1)                       (1)          (1)                                    
      Cornea, Inflammation, Chronic Active                                       1 (100%)                                           
   Harderian Gland                                    (3)          (3)          (5)          (3)                                    
      Inflammation, Chronic Active                                               1 (20%)                                            
   Zymbal's Gland                                     (1)                                                                           
      Hypertrophy                                      1 (100%)                                                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (60)         (60)         (60)         (60)                                   
      Cyst                                             4 (7%)       2 (3%)                                                          
      Hydronephrosis                                                                          1 (2%)                                
      Infarct                                                                                 1 (2%)                                
      Inflammation, Chronic                           11 (18%)     16 (27%)     11 (18%)     14 (23%)                               
      Inflammation, Chronic Active                     2 (3%)                    1 (2%)                                             
      Metaplasia, Osseous                              2 (3%)       3 (5%)       1 (2%)                                             
      Nephropathy                                     52 (87%)     47 (78%)     44 (73%)     38 (63%)                               
      Pigmentation                                                  1 (2%)                                                          
      Artery, Inflammation, Chronic Active                                                    1 (2%)                                

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

                                                             Page   12                                                              
NTP Experiment-Test: 05068-10         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              CODEINE                                          Date: 04/02/96  
Route: DOSED FEED                                                                                                 Time: 23:43:31  
____________________________________________________________________________________________________________________________________

         B6C3F1 MICE MALE                          0 PPM        750 PPM      1500 PPM     3000 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
      Bilateral, Hydronephrosis                                                  1 (2%)                                             
      Capsule, Fibrosis                                             1 (2%)                                                          
      Renal Tubule, Degeneration, Hyaline              1 (2%)                                                                       
      Renal Tubule, Hyperplasia                        2 (3%)                                                                       
      Renal Tubule, Necrosis                                        1 (2%)                                                          
      Renal Tubule, Pigmentation                                    1 (2%)                                                          
   Urinary Bladder                                    (60)         (60)         (60)         (59)                                   
      Dilatation                                                    2 (3%)       2 (3%)       3 (5%)                                
      Infiltration Cellular, Lymphocyte               16 (27%)      9 (15%)      9 (15%)      6 (10%)                               
      Inflammation, Acute                                                                     1 (2%)                                
      Inflammation, Chronic Active                     1 (2%)                    1 (2%)                                             
                                                                                                                                    

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

                                                             Page   13                                                              
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