https://ntp.niehs.nih.gov/go/12907

TDMS Study 56348-03 Pathology Tables

NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57
       Facility:  Battelle Columbus Laboratory
       Chemical CAS #:  5392-40-5
       Lock Date:  03/25/99
       Cage Range:  All
       Reasons For Removal:    All
       Removal Date Range:     All
       Treatment Groups:       Include All
a  Number of animals examined microscopically at site and number of animals with lesion
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
                                                              Page   1
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50           50                        
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                12           10           11           11           12                        
    Natural Death                                      3                         3            3            2                        
  Survivors                                                                                                                         
    Terminal Sacrifice                                34           40           36           36           36                        
    Natural Death                                      1                                                                            
  Animals Examined Microscopically                    50           50           50           50           50                        
____________________________________________________________________________________________________________________________________
 ALIMENTARY SYSTEM                                                                                                                  
   Intestine Large, Colon                             (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                                            1 [1.0]                               
      Parasite Metazoan                                2            2                                      2                        
      Ulcer                                                                                   1 [2.0]                               
   Intestine Large, Rectum                            (50)         (50)         (50)         (50)         (50)                      
      Parasite Metazoan                                7            4            1            6            3                        
   Intestine Large, Cecum                             (50)         (50)         (50)         (50)         (49)                      
      Inflammation                                                               1 [1.0]                                            
   Intestine Small, Duodenum                          (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                               1 [1.0]                                            
      Parasite Metazoan                                                                                    1                        
   Intestine Small, Jejunum                           (50)         (50)         (50)         (49)         (50)                      
      Dysplasia                                                                  1 [4.0]                                            
      Inflammation                                                               1 [1.0]                                            
      Polyp Inflammatory                                                         1 [4.0]                                            
      Ulcer                                                                                                1 [4.0]                  
      Lymphatic, Cyst                                                            1 [4.0]                                            
   Intestine Small, Ileum                             (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                  1 [1.0]                                                         
   Liver                                              (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                                   3 [1.3]      1 [1.0]      1 [1.0]      1 [1.0]                  
      Basophilic Focus                                42           48           44           45           42                        
      Clear Cell Focus                                              1                                                               
      Degeneration, Cystic                             1 [1.0]      2 [1.0]                                                         
      Eosinophilic Focus                               8            8            7            3            9                        
      Fatty Change                                                                            1 [4.0]      4 [1.5]                  
      Fibrosis                                                                   1 [1.0]                                            
      Hematopoietic Cell Proliferation                 1 [1.0]      3 [1.0]                                                         
      Hepatodiaphragmatic Nodule                      10            8            8            4            5                        
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    2                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation                                    40 [1.9]     44 [2.0]     44 [1.7]     41 [1.8]     43 [1.9]                  
      Mixed Cell Focus                                16           18           11           16           15                        
      Necrosis                                                                   2 [1.5]                   1 [1.0]                  
      Vacuolization Cytoplasmic                        5 [1.0]     12 [1.0]      7 [1.0]      4 [1.5]      6 [1.0]                  
      Bile Duct, Hyperplasia                          25 [1.2]     15 [1.2]     17 [1.4]     13 [1.3]     13 [1.4]                  
      Centrilobular, Degeneration                      5 [2.2]      6 [1.2]      9 [1.8]      7 [1.3]      7 [1.4]                  
   Mesentery                                          (10)         (5)          (1)          (5)          (7)                       
      Hemorrhage                                       1 [4.0]                                                                      
      Inflammation                                                  2 [1.5]                                                         
      Thrombosis                                                                                           1 [1.0]                  
      Fat, Necrosis                                    8 [2.5]      3 [2.3]      1 [2.0]      4 [2.3]      5 [2.0]                  
   Pancreas                                           (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                          8 [1.1]     12 [1.1]     20 [1.1]      8 [1.1]     10 [1.2]                  
      Cyst                                                          2 [1.0]                                                         
      Cytoplasmic Alteration                           2 [1.0]      1 [1.0]      1 [1.0]                   2 [1.0]                  
      Hyperplasia                                      1 [2.0]      2 [1.0]      2 [1.5]                                            
      Inflammation                                     1 [1.0]                   1 [1.0]                                            
      Metaplasia, Hepatocyte                                                                               1 [1.0]                  
   Salivary Glands                                    (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                          2 [1.0]                                             1 [1.0]                  
      Inflammation                                                  2 [1.0]                                                         
   Stomach, Forestomach                               (50)         (49)         (50)         (50)         (50)                      
      Edema                                            1 [2.0]                                                                      
      Hyperplasia                                                                                          1 [1.0]                  
      Inflammation                                                               1 [2.0]                   1 [2.0]                  
      Ulcer                                            2 [2.0]                   2 [1.0]                   1 [1.0]                  
      Epithelium, Hyperplasia                          6 [1.5]      1 [2.0]      4 [2.0]      3 [1.3]      1 [2.0]                  
   Stomach, Glandular                                 (50)         (50)         (50)         (50)         (50)                      
      Erosion                                          2 [1.0]      1 [1.0]      1 [1.0]      4 [1.0]      2 [1.0]                  
      Fibrosis                                         1 [1.0]                                                                      
      Inflammation                                                               1 [1.0]                                            
      Mineralization                                                1 [1.0]      1 [1.0]                                            
      Ulcer                                                                                   1 [1.0]                               
      Epithelium, Mineralization                       1 [1.0]                                                                      
   Tooth                                                                        (1)          (2)          (2)                       
      Inflammation                                                                            2 [2.5]      1 [4.0]                  
      Malformation                                                                            1                                     
      Peridontal Tissue, Inflammation                                            1 [2.0]                   1 [2.0]                  
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Blood Vessel                                       (50)         (50)         (50)         (50)         (50)                      
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    3                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM - CONT                                                                                                        
      Inflammation                                                                                         1 [1.0]                  
   Heart                                              (50)         (50)         (50)         (50)         (50)                      
      Cardiomyopathy                                  41 [1.1]     48 [1.1]     40 [1.1]     42 [1.1]     39 [1.1]                  
      Fibrosis                                                                                1 [1.0]                               
      Hemorrhage                                                                 1 [1.0]                                            
      Necrosis                                                                                             1 [2.0]                  
      Thrombosis                                                                 1 [1.0]                   1 [1.0]                  
____________________________________________________________________________________________________________________________________
 ENDOCRINE SYSTEM                                                                                                                   
   Adrenal Cortex                                     (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                                   1 [1.0]      1 [2.0]      3 [1.0]     10 [1.0]                  
      Atrophy                                                                    1 [3.0]                                            
      Atypia Cellular                                                                                      1 [1.0]                  
      Degeneration, Cystic                                                                    1 [2.0]                               
      Hyperplasia                                     14 [1.1]     16 [1.2]     13 [1.2]     12 [1.3]      8 [1.1]                  
      Hypertrophy                                     10 [1.5]      4 [1.5]      3 [1.3]      3 [1.7]      4 [1.3]                  
      Thrombosis                                                                 1 [2.0]                                            
      Vacuolization Cytoplasmic                        1 [2.0]      2 [1.0]      6 [1.8]      2 [1.5]                               
   Adrenal Medulla                                    (49)         (50)         (50)         (50)         (50)                      
      Hyperplasia                                      8 [1.3]      3 [1.3]      4 [1.0]      3 [2.0]      3 [1.7]                  
      Infiltration Cellular, Lymphocyte                             1 [1.0]                                                         
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)         (49)                      
      Hyperplasia                                      1 [3.0]                                                                      
   Parathyroid Gland                                  (43)         (43)         (40)         (43)         (47)                      
      Hyperplasia                                      1 [2.0]                                                                      
   Pituitary Gland                                    (50)         (50)         (50)         (50)         (49)                      
      Cyst                                             1 [3.0]                   2 [3.5]      3 [1.3]      3 [1.3]                  
      Hyperplasia                                                                             1 [4.0]                               
      Pars Distalis, Cyst                              1 [2.0]      1 [2.0]                   1 [1.0]                               
      Pars Distalis, Hyperplasia                      27 [2.3]     29 [2.1]     31 [1.9]     23 [1.8]     27 [2.0]                  
      Pars Intermedia, Hyperplasia                                  1 [2.0]      1 [1.0]                                            
   Thyroid Gland                                      (50)         (50)         (50)         (50)         (50)                      
      C-Cell, Hyperplasia                             45 [1.4]     45 [1.4]     39 [1.2]     43 [1.5]     36 [1.2]                  
      Follicular Cell, Hyperplasia                                  1 [1.0]      2 [1.5]                                            
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    4                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Clitoral Gland                                     (49)         (49)         (49)         (50)         (49)                      
      Hyperplasia                                      7 [2.3]     17 [2.4]      8 [1.4]     15 [2.4]      4 [2.5]                  
      Inflammation                                    13 [1.3]     22 [1.3]     20 [1.1]     19 [1.1]     24 [1.2]                  
      Metaplasia                                                                 1 [1.0]                                            
      Bilateral, Cyst                                               1 [2.0]                                                         
      Duct, Cyst                                       5 [1.6]      5 [1.8]      3 [2.0]      6 [1.5]      4 [2.0]                  
   Ovary                                              (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                                    2 [3.0]      1 [4.0]                               
      Cyst                                             3 [3.3]     11 [2.0]      6 [2.5]      4 [2.5]      5 [2.4]                  
      Infiltration Cellular, Lymphocyte                                                       1 [2.0]      2 [2.5]                  
   Uterus                                             (50)         (50)         (50)         (50)         (50)                      
      Fibrosis                                         1 [4.0]                                                                      
      Hemorrhage                                                    1 [2.0]                   1 [4.0]                               
      Hyperplasia                                                                                          1 [4.0]                  
      Hyperplasia, Cystic                              1 [2.0]                                                                      
      Inflammation                                                  1 [3.0]                                                         
      Cervix, Prolapse                                                                        1                                     
      Endometrium, Hyperplasia, Cystic                 9 [2.0]     12 [1.9]     15 [1.6]      9 [2.0]     14 [1.4]                  
   Vagina                                                          (2)          (1)          (2)                                    
      Dilatation                                                    1 [4.0]                                                         
      Hyperplasia                                                                             1 [3.0]                               
      Hypertrophy                                                   1 [2.0]                                                         
      Inflammation, Acute                                                        1 [3.0]                                            
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                      1 [3.0]                                                                      
      Atrophy                                          1 [1.0]      1 [1.0]                   2 [1.0]      1 [1.0]                  
      Hyperplasia                                     11 [2.5]      9 [2.7]     12 [2.1]     10 [2.7]     10 [2.4]                  
      Myelofibrosis                                    1 [3.0]                   1 [2.0]                   1 [2.0]                  
      Necrosis                                                                                1 [3.0]                               
   Lymph Node                                         (7)          (4)          (7)          (10)         (5)                       
      Lumbar, Hyperplasia, Histiocytic                              1 [1.0]                                                         
      Mediastinal, Congestion                                       1 [2.0]                                                         
      Mediastinal, Hyperplasia, Plasma Cell                                                   1 [3.0]                               
   Lymph Node, Mandibular                             (50)         (50)         (50)         (50)         (50)                      
      Ectasia                                                      10 [1.1]      3 [1.0]      5 [1.0]      7 [1.6]                  
      Hyperplasia, Plasma Cell                         6 [1.8]     17 [1.9]     17 [2.0]      7 [2.1]     17 [2.0]                  
      Necrosis                                                                                             1 [1.0]                  
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (50)         (50)                      
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    5                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Atrophy                                                       1 [3.0]                                                         
      Ectasia                                                                    1 [2.0]                                            
      Hyperplasia, Lymphoid                                                      1 [2.0]                                            
   Spleen                                             (50)         (50)         (50)         (50)         (50)                      
      Accessory Spleen                                              1                                                               
      Ectopic Tissue                                                1 [2.0]                                                         
      Fibrosis                                         1 [2.0]      1 [2.0]                                                         
      Granuloma                                        1 [3.0]                                                                      
      Hematopoietic Cell Proliferation                11 [1.8]     11 [2.3]      8 [1.6]      5 [2.8]      5 [1.6]                  
      Hemorrhage                                                                              1 [4.0]                               
      Hyperplasia, Histiocytic                         1 [2.0]                                                                      
      Hyperplasia, Adenomatous                                                                             1 [4.0]                  
      Infarct                                          1 [3.0]                                                                      
      Infiltration Cellular, Lipocyte                                                                      1 [1.0]                  
      Necrosis                                                                   1 [4.0]                                            
      Pigmentation                                     1 [2.0]                   1 [2.0]      3 [2.3]                               
      Red Pulp, Depletion Cellular                     1 [4.0]                                                                      
   Thymus                                             (49)         (47)         (49)         (48)         (49)                      
      Atrophy                                         45 [3.3]     46 [3.5]     45 [3.3]     44 [3.6]     46 [3.4]                  
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Mammary Gland                                      (50)         (50)         (50)         (50)         (50)                      
      Galactocele                                      3 [2.0]      1 [3.0]      2 [4.0]      3 [2.7]                               
      Hyperplasia                                                   1 [3.0]      4 [1.3]                   1 [2.0]                  
      Hyperplasia, Focal                               4 [1.3]      5 [1.2]     10 [1.2]      6 [2.5]      3 [1.3]                  
      Hyperplasia, Lobular                                                       1 [1.0]                                            
   Skin                                               (50)         (50)         (50)         (50)         (50)                      
      Cyst Epithelial Inclusion                                                  1                                                  
      Fibrosis                                                      1 [4.0]                                                         
      Hyperkeratosis                                   1 [1.0]                                                                      
      Hyperplasia                                      1 [2.0]                                                                      
      Inflammation                                     1 [1.0]                                                                      
      Dermis, Fibrosis                                 1 [4.0]                                                                      
      Subcutaneous Tissue, Inflammation                             1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (50)         (50)         (50)         (50)                      
      Osteopetrosis                                    3 [2.3]      3 [2.3]     12 [2.0]      5 [2.8]      8 [3.1]                  
____________________________________________________________________________________________________________________________________
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    6                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
 NERVOUS SYSTEM                                                                                                                     
   Brain                                              (50)         (50)         (50)         (50)         (50)                      
      Hemorrhage                                       3 [2.3]      2 [2.5]      4 [2.3]      4 [2.3]                               
      Necrosis                                                      1 [2.0]                   4 [2.0]                               
   Spinal Cord                                                                               (1)                                    
      Hemorrhage                                                                              1 [3.0]                               
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (50)         (50)         (50)         (50)                      
      Fibrosis                                                                                             1 [1.0]                  
      Hemorrhage                                       2 [1.0]                   1 [1.0]      1 [1.0]      1 [1.0]                  
      Hyperplasia, Lymphoid                                                      1 [2.0]                                            
      Inflammation                                     9 [1.2]      7 [1.4]     17 [1.0]      9 [1.0]      9 [1.0]                  
      Alveolar Epithelium, Hyperplasia                 9 [1.6]     10 [1.3]      9 [1.2]     10 [1.7]     11 [1.8]                  
   Nose                                               (50)         (50)         (50)         (50)         (50)                      
      Foreign Body                                     3            1            4            1            3                        
      Inflammation                                     4 [1.3]      5 [1.0]      5 [1.2]      2 [2.0]      3 [1.3]                  
   Trachea                                            (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                     1 [1.0]      1 [1.0]      3 [1.0]      1 [1.0]      1 [1.0]                  
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
   Eye                                                (2)          (3)          (1)                       (2)                       
      Cataract                                         2 [3.5]      2 [3.0]      1 [3.0]                   1 [2.0]                  
      Cornea, Inflammation                                          1 [4.0]                                                         
      Retina, Degeneration                             2 [4.0]      2 [2.0]      1 [3.0]                   1 [3.0]                  
   Harderian Gland                                                                                        (1)                       
      Atrophy                                                                                              1 [4.0]                  
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
   Kidney                                             (50)         (50)         (50)         (50)         (50)                      
      Accumulation, Hyaline Droplet                                 1 [3.0]                   1 [1.0]                               
      Cyst                                                          1 [3.0]                                1 [2.0]                  
      Hydronephrosis                                                                          2 [1.5]      1 [1.0]                  
      Inflammation                                     1 [1.0]      1 [2.0]                                1 [3.0]                  
      Mineralization                                  41 [1.0]     43 [1.0]     43 [1.0]     38 [1.0]     41 [1.0]                  
      Necrosis                                                                                             2 [3.0]                  
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    7                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                      UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT                                                                                                               
      Nephropathy                                     41 [1.0]     44 [1.1]     45 [1.0]     48 [1.0]     44 [1.0]                  
      Pigmentation                                     2 [2.0]      1 [1.0]      4 [1.3]                   1 [2.0]                  
      Renal Tubule, Hyperplasia                                     1 [1.0]                                1 [1.0]                  
      Transitional Epithelium, Hyperplasia                                                    1 [1.0]                               
   Urinary Bladder                                    (50)         (50)         (50)         (50)         (50)                      
      Calculus Gross Observation                                                                           1                        
      Hemorrhage                                       1 [3.0]                   1 [2.0]                                            
      Inflammation                                                                            1 [2.0]                               
      Ulcer                                                                                   1 [2.0]                               
      Transitional Epithelium, Hyperplasia                                                    1 [2.0]      1 [4.0]                  
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    8                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50           50                        
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                18           22           15           11           10                        
    Natural Death                                      2            6            3            4            6                        
  Survivors                                                                                                                         
    Terminal Sacrifice                                30           22           32           35           34                        
  Animals Examined Microscopically                    50           50           50           50           50                        
____________________________________________________________________________________________________________________________________
 ALIMENTARY SYSTEM                                                                                                                  
   Intestine Large, Colon                             (50)         (50)         (50)         (50)         (50)                      
      Dysplasia                                                                               1 [4.0]                               
      Inflammation                                                               1 [4.0]                                            
      Parasite Metazoan                                4                         4            2                                     
      Ulcer                                                                      1 [4.0]                                            
      Artery, Inflammation                                                                    1 [3.0]                               
      Lymphoid Tissue, Hyperplasia                                  1 [1.0]                                                         
   Intestine Large, Rectum                            (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                     1 [1.0]                                             1 [3.0]                  
      Parasite Metazoan                                7            3            7            8            8                        
   Intestine Large, Cecum                             (50)         (50)         (50)         (49)         (50)                      
      Edema                                                                      1 [2.0]                                            
      Inflammation                                                                                         2 [3.5]                  
      Parasite Metazoan                                                          1                                                  
      Ulcer                                            1 [1.0]      2 [3.5]                                                         
   Intestine Small, Duodenum                          (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                               1 [1.0]                                            
   Intestine Small, Jejunum                           (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                     1 [3.0]      3 [2.0]      2 [2.5]      1 [2.0]      1 [2.0]                  
      Inflammation, Granulomatous                                   1 [4.0]                                                         
   Intestine Small, Ileum                             (50)         (50)         (49)         (50)         (50)                      
      Erosion                                                                                 1 [4.0]                               
      Inflammation                                                  2 [1.5]      1 [1.0]      1 [4.0]      2 [2.0]                  
      Parasite Metazoan                                             1                         1                                     
   Liver                                              (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                                   5 [1.0]      1 [1.0]      4 [1.0]      1 [1.0]                  
      Basophilic Focus                                33           24           33           33           29                        
      Clear Cell Focus                                14            7           11           16            9                        
      Degeneration, Cystic                             3 [1.0]      2 [1.0]      1 [1.0]      1 [1.0]      5 [1.0]                  
      Developmental Malformation                                                              1                                     
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page    9                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
      Eosinophilic Focus                               6            3            5            3            6                        
      Fatty Change                                     2 [2.0]      4 [1.5]                   1 [3.0]                               
      Hematopoietic Cell Proliferation                              3 [1.3]      1 [2.0]      1 [1.0]      1 [1.0]                  
      Hepatodiaphragmatic Nodule                       6            3            7            4            7                        
      Inflammation                                    21 [1.0]     22 [1.0]     28 [1.1]     27 [1.0]     28 [1.1]                  
      Mixed Cell Focus                                 5            1            8            5            7                        
      Necrosis                                         1 [1.0]                                             1 [1.0]                  
      Vacuolization Cytoplasmic                        7 [1.0]      6 [1.0]      7 [1.0]      8 [1.3]      3 [1.0]                  
      Bile Duct, Fibrosis                                                                                  1 [1.0]                  
      Bile Duct, Hyperplasia                          48 [1.8]     45 [1.7]     50 [1.8]     45 [1.7]     47 [1.7]                  
      Centrilobular, Degeneration                     22 [2.0]     19 [1.9]     14 [2.3]     15 [1.9]     16 [2.1]                  
   Mesentery                                          (8)          (13)         (11)         (11)         (5)                       
      Inflammation                                                  1 [3.0]      1 [3.0]                                            
      Fat, Necrosis                                    7 [2.7]     11 [2.9]      7 [3.0]      9 [2.4]      3 [2.3]                  
   Oral Mucosa                                                     (1)          (2)                                                 
      Inflammation, Chronic Active                                               1 [3.0]                                            
   Pancreas                                           (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                         22 [1.5]     18 [1.2]     17 [1.1]     14 [1.4]     16 [1.3]                  
      Cytoplasmic Alteration                           1 [1.0]      2 [1.0]      3 [1.0]      2 [1.0]      1 [1.0]                  
      Hyperplasia                                      3 [1.3]      2 [3.0]      7 [2.0]                   2 [2.0]                  
      Inflammation                                     2 [1.0]      1 [1.0]                                                         
      Metaplasia, Hepatocyte                                                                  2 [1.0]                               
      Thrombosis                                                    1 [2.0]                                                         
      Artery, Inflammation                                          1 [2.0]      3 [2.7]                   2 [3.5]                  
   Salivary Glands                                    (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                          1 [1.0]      1 [3.0]      2 [1.5]                   1 [2.0]                  
      Cytoplasmic Alteration                                                                               1 [1.0]                  
   Stomach, Forestomach                               (50)         (50)         (50)         (50)         (50)                      
      Edema                                            1 [2.0]      1 [3.0]      1 [3.0]      2 [1.5]                               
      Inflammation                                                  1 [1.0]      3 [1.7]      1 [3.0]      2 [2.5]                  
      Ulcer                                            1 [1.0]      3 [1.3]      2 [2.5]      3 [1.7]      3 [2.7]                  
      Epithelium, Hyperplasia                          1 [2.0]      6 [1.8]      7 [1.7]      8 [1.8]      3 [2.0]                  
      Epithelium, Hyperplasia, Basal Cell              1 [2.0]      1 [1.0]                                1 [2.0]                  
   Stomach, Glandular                                 (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                                                              1 [1.0]                  
      Erosion                                          2 [1.0]      7 [1.0]      3 [1.0]      2 [1.0]      2 [1.0]                  
      Inflammation                                                               1 [1.0]      1 [1.0]      1 [3.0]                  
      Necrosis                                                                                             1 [3.0]                  
      Thrombosis                                                                                           1 [2.0]                  
      Ulcer                                            3 [1.0]      4 [1.5]      2 [1.5]      5 [1.0]      1 [1.0]                  
      Epithelium, Ulcer                                                                       1 [1.0]                               
   Tongue                                             (1)                       (1)          (1)                                    
      Inflammation                                                               1 [4.0]                                            
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   10                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
   Tooth                                              (1)          (1)          (1)                                                 
      Degeneration                                                  1 [2.0]                                                         
      Malformation                                                               1 [4.0]                                            
      Peridontal Tissue, Inflammation                  1 [1.0]      1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Blood Vessel                                       (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                                            2 [1.5]                               
      Jugular Vein, Thrombosis                                                   1 [2.0]                                            
   Heart                                              (50)         (50)         (50)         (50)         (50)                      
      Cardiomyopathy                                  39 [1.3]     43 [1.3]     45 [1.5]     50 [1.5]     47 [1.6]                  
      Fibrosis                                                                                             1 [2.0]                  
      Inflammation                                                  2 [1.5]                                1 [1.0]                  
      Thrombosis                                                    6 [1.8]      2 [2.0]      2 [1.5]      2 [2.5]                  
      Valve, Inflammation                                           1 [1.0]                                                         
____________________________________________________________________________________________________________________________________
 ENDOCRINE SYSTEM                                                                                                                   
   Adrenal Cortex                                     (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                                                1 [1.0]                   1 [1.0]                  
      Atrophy                                                                                              1 [3.0]                  
      Hematopoietic Cell Proliferation                              2 [1.0]                                                         
      Hyperplasia                                     12 [1.0]     13 [1.2]     20 [1.3]     11 [1.2]     14 [1.1]                  
      Hypertrophy                                                                             1 [1.0]                               
      Necrosis                                         3 [1.7]      1 [1.0]      1 [3.0]                   2 [3.0]                  
      Thrombosis                                                    1 [1.0]                                                         
      Vacuolization Cytoplasmic                        4 [2.0]      7 [1.1]      1 [3.0]      2 [1.0]      3 [1.0]                  
   Adrenal Medulla                                    (50)         (50)         (50)         (50)         (50)                      
      Hyperplasia                                     12 [2.0]     16 [1.4]     23 [2.0]     14 [2.0]     15 [1.6]                  
      Necrosis                                                                                             1 [4.0]                  
      Thrombosis                                                                                           1 [2.0]                  
   Islets, Pancreatic                                 (49)         (50)         (50)         (50)         (50)                      
      Hyperplasia                                      1 [2.0]                                                                      
   Parathyroid Gland                                  (48)         (45)         (47)         (45)         (45)                      
      Hyperplasia                                      1 [1.0]                   2 [1.0]      1 [1.0]                               
   Pituitary Gland                                    (50)         (50)         (50)         (50)         (49)                      
      Atrophy                                                                                              1 [3.0]                  
      Cyst                                             5 [1.4]      4 [1.0]      5 [1.2]      4 [2.5]      2 [1.0]                  
      Necrosis                                         1 [1.0]                                                                      
      Pars Distalis, Cyst                                                                     1 [2.0]                               
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   11                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT                                                                                                             
      Pars Distalis, Hemorrhage                                                                            1 [4.0]                  
      Pars Distalis, Hyperplasia                      15 [1.7]     22 [1.9]     24 [1.7]     19 [1.9]     18 [1.7]                  
      Pars Intermedia, Hyperplasia                                                            1 [1.0]      1 [2.0]                  
      Pars Nervosa, Hyperplasia                                     1 [1.0]                                                         
      Rathke's Cleft, Hyperplasia                                   1 [4.0]                                                         
   Thyroid Gland                                      (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                                                                         1 [1.0]                  
      C-Cell, Hyperplasia                             32 [1.4]     38 [1.3]     41 [1.4]     41 [1.4]     34 [1.5]                  
      Follicular Cell, Hyperplasia                     1 [1.0]      2 [2.0]      1 [1.0]      4 [1.0]      3 [1.7]                  
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Coagulating Gland                                                            (1)          (1)          (1)                       
      Inflammation                                                               1 [2.0]                                            
   Epididymis                                         (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                                                              1 [4.0]                  
      Inflammation                                     1 [1.0]                   3 [1.0]      1 [1.0]      2 [1.0]                  
   Preputial Gland                                    (50)         (50)         (49)         (50)         (50)                      
      Hyperplasia                                      2 [2.0]      2 [2.0]                   1 [2.0]      2 [3.0]                  
      Inflammation                                    47 [1.9]     48 [1.9]     47 [1.9]     49 [2.0]     47 [1.9]                  
      Duct, Ectasia                                    1 [2.0]                   2 [3.0]                   1 [2.0]                  
   Prostate                                           (50)         (50)         (50)         (50)         (50)                      
      Cyst                                             4 [2.0]      1 [2.0]      8 [2.4]      1 [1.0]      2 [2.0]                  
      Hyperplasia                                      2 [2.0]      3 [1.7]                   3 [2.0]                               
      Inflammation                                                                            1 [1.0]      2 [1.5]                  
      Inflammation, Chronic Active                    29 [1.5]     33 [1.5]     30 [1.3]     28 [1.3]     22 [1.6]                  
      Dorsal, Inflammation, Chronic Active             1 [1.0]                   1 [1.0]                                            
      Ventral, Hyperplasia                             1 [3.0]                                                                      
   Seminal Vesicle                                    (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                                                 1 [2.0]                               
      Hyperplasia                                                                             1 [1.0]                               
      Inflammation                                     1 [1.0]                                                                      
   Testes                                             (50)         (50)         (50)         (50)         (50)                      
      Angiectasis                                                                             1 [4.0]                               
      Atrophy                                          2 [4.0]      2 [4.0]                   3 [3.3]      1 [4.0]                  
      Hyperplasia                                                   1 [1.0]                                                         
      Interstitial Cell, Hyperplasia                   4 [2.3]      7 [2.0]      4 [1.0]      9 [1.0]      5 [1.2]                  
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   12                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                                    3 [1.7]      1 [1.0]      2 [2.0]                  
      Hemorrhage                                                                                           1 [2.0]                  
      Hyperplasia                                     14 [2.6]     16 [2.9]     20 [2.3]     14 [2.5]     13 [2.4]                  
      Myelofibrosis                                    2 [2.5]      2 [1.0]      1 [4.0]      1 [2.0]                               
      Necrosis                                                      1 [4.0]                                                         
   Lymph Node                                         (15)         (20)         (10)         (10)         (12)                      
      Deep Cervical, Hyperplasia, Plasma Cell                                                              1 [2.0]                  
      Inguinal, Ectasia                                                                                    1 [4.0]                  
      Inguinal, Necrosis                                            1 [4.0]                                                         
      Mediastinal, Ectasia                                          1 [2.0]                                1 [4.0]                  
      Mediastinal, Necrosis                                         2 [4.0]                                                         
      Renal, Necrosis                                               1 [4.0]                                                         
   Lymph Node, Mandibular                             (50)         (49)         (50)         (50)         (50)                      
      Atrophy                                                       1 [3.0]                                                         
      Ectasia                                          4 [1.0]      3 [1.3]      2 [1.5]      9 [1.3]      1 [1.0]                  
      Hyperplasia                                                   1 [2.0]                                                         
      Hyperplasia, Plasma Cell                        17 [2.0]     13 [2.2]     13 [1.9]     18 [2.1]     20 [2.1]                  
      Inflammation                                                                                         1 [2.0]                  
      Necrosis                                         1 [1.0]      1 [4.0]                                                         
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (50)         (50)                      
      Atrophy                                                       1 [4.0]                   1 [2.0]                               
      Ectasia                                          3 [1.3]      1 [3.0]                   5 [3.0]      1 [1.0]                  
      Inflammation                                                               1 [2.0]                                            
      Inflammation, Granulomatous                                   1 [4.0]                                                         
      Necrosis                                                      1 [4.0]                   1 [1.0]                               
   Spleen                                             (50)         (50)         (50)         (50)         (49)                      
      Accessory Spleen                                                                        1            1                        
      Angiectasis                                                                                          1 [2.0]                  
      Congestion                                                    1 [1.0]                   1 [2.0]                               
      Fibrosis                                         2 [1.5]      2 [1.0]      2 [2.0]      2 [1.0]      1 [4.0]                  
      Hematopoietic Cell Proliferation                 3 [1.3]      8 [3.0]      2 [2.5]      4 [3.3]      5 [1.6]                  
      Hemorrhage                                                                              1 [3.0]                               
      Infarct                                          2 [1.5]      2 [2.0]                   1 [4.0]      2 [2.5]                  
      Necrosis                                                      2 [1.5]                                                         
      Pigmentation                                                               2 [2.5]      1 [2.0]      1 [2.0]                  
      Lymphoid Follicle, Atrophy                                    2 [2.5]      1 [4.0]      1 [2.0]                               
      Red Pulp, Depletion Cellular                                  1 [1.0]      2 [3.0]                                            
   Thymus                                             (50)         (47)         (49)         (47)         (49)                      
      Atrophy                                         45 [3.4]     38 [3.6]     47 [3.5]     44 [3.6]     45 [3.5]                  
      Inflammation                                                  1 [4.0]                                                         
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   13                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Epithelial Cell, Hyperplasia                                                                         1 [3.0]                  
      Vein, Inflammation                                                                                   1 [3.0]                  
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Mammary Gland                                      (50)         (50)         (50)         (49)         (50)                      
      Hyperplasia                                      3 [1.3]      7 [1.7]      5 [1.2]      9 [1.2]      6 [1.5]                  
   Skin                                               (50)         (50)         (50)         (50)         (50)                      
      Hemorrhage                                                    1 [2.0]                                                         
      Hyperkeratosis                                                4 [2.0]                   3 [2.7]                               
      Hyperplasia                                      1 [3.0]      1 [2.0]                   1 [2.0]                               
      Inflammation                                                  3 [3.0]      1 [4.0]      4 [2.0]                               
      Inflammation, Chronic Active                     1 [3.0]                                                                      
      Parakeratosis                                                                           1 [4.0]                               
      Ulcer                                                                                   2 [1.0]                               
      Dermis, Fibrosis                                                                        1 [4.0]                               
      Dermis, Necrosis                                                                        1 [2.0]                               
      Epidermis, Hyperplasia                           2 [3.0]      1 [2.0]                                                         
      Epidermis, Inflammation, Acute                   1 [2.0]      1 [2.0]                                                         
      Subcutaneous Tissue, Fibrosis                                              1 [2.0]      1 [4.0]                               
      Subcutaneous Tissue, Mineralization                                                     1 [2.0]                               
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (50)         (50)         (50)         (50)                      
      Necrosis                                                                                1 [1.0]                               
      Osteopetrosis                                                              1 [2.0]      1 [3.0]                               
____________________________________________________________________________________________________________________________________
 NERVOUS SYSTEM                                                                                                                     
   Brain                                              (50)         (50)         (50)         (50)         (50)                      
      Hemorrhage                                       5 [1.2]      9 [1.6]      1 [1.0]      2 [2.5]      2 [3.0]                  
      Necrosis                                                      1 [2.0]                   1 [1.0]      1 [2.0]                  
   Spinal Cord                                                     (2)                                                              
      Hemorrhage                                                    2 [3.0]                                                         
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (50)         (50)         (50)         (50)                      
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   14                                                              
NTP Experiment-Test: 56348-03         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 07/05/01    
Route: DOSED FEED                                                   CITRAL                                        Time: 15:32:57    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                        UNTREAT      VEHICLE      1000 PPM     2000 PPM     4000 PPM                  
                                                      CONTROL      CONTROL                                                          
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT                                                                                                           
      Embolus, Cartilagenous                                                     1 [4.0]                                            
      Foreign Body                                     1                                                                            
      Hemorrhage                                       6 [1.0]      2 [1.0]      1 [1.0]                   2 [1.0]                  
      Inflammation                                    12 [1.3]     12 [1.2]      6 [1.5]      8 [1.0]      5 [1.2]                  
      Necrosis                                                      1 [2.0]                                                         
      Thrombosis                                       1 [1.0]      3 [1.0]                                1 [1.0]                  
      Alveolar Epithelium, Hyperplasia                 7 [2.0]      6 [2.2]     10 [1.6]     10 [1.7]     11 [2.2]                  
      Artery, Inflammation                                          1 [2.0]                                                         
      Bronchiole, Hyperplasia                                                                 1 [1.0]                               
      Bronchus, Hyperplasia                                         1 [1.0]                                                         
      Mediastinum, Inflammation                                     1 [4.0]                                                         
   Nose                                               (50)         (50)         (50)         (50)         (50)                      
      Dysplasia                                                     1 [1.0]                                                         
      Foreign Body                                     7            7            6            9            7                        
      Inflammation                                    13 [1.1]     11 [1.3]      9 [1.1]     14 [1.4]      8 [1.5]                  
   Trachea                                            (50)         (50)         (50)         (50)         (50)                      
      Inflammation                                     1 [1.0]      1 [1.0]                                                         
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
   Eye                                                (1)          (3)          (3)          (2)          (3)                       
      Cataract                                         1 [2.0]      3 [2.7]      2 [2.5]      1 [2.0]      3 [3.3]                  
      Retina, Degeneration                             1 [3.0]      3 [3.3]      2 [3.0]      1 [2.0]      3 [4.0]                  
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
   Kidney                                             (50)         (50)         (50)         (50)         (50)                      
      Accumulation, Hyaline Droplet                                 2 [1.5]                   2 [1.5]      3 [1.0]                  
      Cyst                                                                                    4 [1.5]                               
      Infarct                                                       3 [2.0]      1 [2.0]                                            
      Mineralization                                  45 [1.0]     42 [1.0]     45 [1.0]     48 [1.4]     50 [2.4]                  
      Necrosis                                                      1 [1.0]                                                         
      Nephropathy                                     49 [1.5]     50 [1.3]     50 [1.5]     49 [1.5]     50 [1.6]                  
      Pigmentation                                     3 [1.7]      2 [2.5]                   2 [1.5]      6 [1.7]                  
      Thrombosis                                                    2 [1.5]                                                         
      Renal Tubule, Hyperplasia                                                  2 [2.0]      1 [1.0]      2 [1.0]                  
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                             Page   15                                                              
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