National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/4138

TDMS Study 93005-04 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: NCTR                                                    MALACHITE GREEN                                   DATE: 06/19/03       
EXPERIMENT: 93005 TEST: 04                                                                                     TIME: 07:25:41       
TEST TYPE:  CHRONIC                                                                                            PAGE:       1        
CONT: 224-93-00001                              ROUTE: DOSED FEED                                              NTP C#: C93005       
PATHOLOGIST: TROTTER, RONALD                                                                                   CAS: 569-64-2        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: NCTR                                                    MALACHITE GREEN                                   DATE: 06/19/03       
EXPERIMENT: 93005 TEST: 04                                                                                     TIME: 07:25:41       
TEST TYPE:  CHRONIC                                                                                                                 
CONT: 224-93-00001                              ROUTE: DOSED FEED                                              NTP C#: C93005       
PATHOLOGIST: TROTTER, RONALD                                                                                   CAS: 569-64-2        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                     MALACHITE GREEN                                                                              
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Hypertrophy Focal                                                                            
Bone: Sternum                          Fibrous Osteodystrophy                                                                       
Clitoral Gland: Duct                   Cyst                                                                                         
Kidney: Glomerulus                     Amyloid Deposition                                                                           
Kidney: Pelvis                         Dilatation                                                                                   
Kidney: Renal Tubule                   Accumulation, Hyaline Droplet                                                                
Liver                                  Infiltration Cellular Lymphocyte                                                             
                                       Necrosis                                                                                     
Lung                                   Proteinosis                                                                                  
Ovary                                  Atrophy                                                                                      
Pancreas: Acinus                       Atrophy                                                                                      
Salivary Glands: Submandibular Gland   Infiltration Cellular Lymphocyte                                                             
Stomach, Forestomach: Epithelium       Hyperplasia Focal                                                                            
Tongue: Artery                         Inflammation Chronic                                                                         
Urinary Bladder                        Inclusion Body Intracytoplasmic                                                              
                                       Infiltration Cellular Lymphocyte                                                             
===============================================================                                                                     
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN    
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/47 (0%)                0/47 (0%)                1/45 (2%)                3/47 (6%)       | 
|POLY-3 RATE (b)    |                  0/44.14                  0/46.38                  1/42.40                  3/44.42         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     2.4%                     6.8%            | 
|TERMINAL (d)       |                  0/39 (0%)                0/44 (0%)                1/40 (3%)                2/40 (5%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      727 (T)                  633             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.019 *                (e)                      P=0.505                  P=0.126         | 
|POLY 3             |                  P=0.018 *                (e)                      P=0.492                  P=0.120         | 
|POLY 1.5           |                  P=0.018 *                (e)                      P=0.491                  P=0.118         | 
|POLY 6             |                  P=0.019 *                (e)                      P=0.495                  P=0.123         | 
|LOGISTIC REGRESSION|                  P=0.020 *                (e)                      P=0.505                  P=0.121         | 
|COCH-ARM / FISHERS |                  P=0.020 *                (e)                      P=0.489                  P=0.121         | 
|ORDER RESTRICTED   |                  P=0.021 *                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  46/47 (98%)              46/47 (98%)              44/45 (98%)              45/47 (96%)     | 
|POLY-3 RATE (b)    |                  46/46.14                 46/47.00                 44/45.00                 45/45.67        | 
|POLY-3 PERCENT (g) |                  99.7%                    97.9%                    97.8%                    98.5%           | 
|TERMINAL (d)       |                  39/39 (100%)             43/44 (98%)              39/40 (98%)              40/40 (100%)    | 
|FIRST INCIDENCE    |                  562                      644                      226                      318             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.494N                 P=0.104N                 P=0.306N                 P=0.379N        | 
|POLY 3             |                  P=0.538N                 P=0.559N                 P=0.550N                 P=0.753N        | 
|POLY 1.5           |                  P=0.511N                 P=0.640N                 P=0.630N                 P=0.691N        | 
|POLY 6             |                  P=0.597N                 P=0.512N                 P=0.503N                 P=0.907N        | 
|LOGISTIC REGRESSION|                  P=0.601N                 P=0.459N                 P=0.710                  P=0.791         | 
|COCH-ARM / FISHERS |                  P=0.348N                 P=0.753N                 P=0.742N                 P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.396N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Femur                                                                                                                      | 
|     Fibrous Osteodystrophy                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                5/48 (10%)               2/48 (4%)                2/48 (4%)       | 
|POLY-3 RATE (b)    |                  4/45.14                  5/46.93                  2/43.58                  2/45.08         | 
|POLY-3 PERCENT (g) |                  8.9%                     10.7%                    4.6%                     4.4%            | 
|TERMINAL (d)       |                  4/40 (10%)               5/44 (11%)               2/40 (5%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.173N                 P=0.560                  P=0.337N                 P=0.325N        | 
|POLY 3             |                  P=0.178N                 P=0.524                  P=0.353N                 P=0.338N        | 
|POLY 1.5           |                  P=0.179N                 P=0.515                  P=0.352N                 P=0.342N        | 
|POLY 6             |                  P=0.174N                 P=0.535                  P=0.349N                 P=0.331N        | 
|LOGISTIC REGRESSION|                  P=0.173N                 P=0.560                  P=0.337N                 P=0.325N        | 
|COCH-ARM / FISHERS |                  P=0.171N                 P=0.500                  P=0.339N                 P=0.339N        | 
|ORDER RESTRICTED   |                  P=0.261N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Sternum                                                                                                                    | 
|     Degeneration Cystic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                2/48 (4%)                4/48 (8%)                3/48 (6%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  2/46.93                  4/43.58                  3/45.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     4.3%                     9.2%                     6.7%            | 
|TERMINAL (d)       |                  0/40 (0%)                2/44 (5%)                4/40 (10%)               3/41 (7%)       | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.110                  P=0.260                  P=0.063                  P=0.126         | 
|POLY 3             |                  P=0.110                  P=0.246                  P=0.056                  P=0.118         | 
|POLY 1.5           |                  P=0.109                  P=0.243                  P=0.056                  P=0.117         | 
|POLY 6             |                  P=0.113                  P=0.250                  P=0.057                  P=0.121         | 
|LOGISTIC REGRESSION|                  (e)                      P=0.260                  P=0.063                  P=0.126         | 
|COCH-ARM / FISHERS |                  P=0.114                  P=0.247                  P=0.059                  P=0.121         | 
|ORDER RESTRICTED   |                  P=0.062                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Sternum                                                                                                                    | 
|     Fibrous Osteodystrophy                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  12/48 (25%)              14/48 (29%)              5/48 (10%)               5/48 (10%)      | 
|POLY-3 RATE (b)    |                  12/45.14                 14/46.93                 5/43.58                  5/45.08         | 
|POLY-3 PERCENT (g) |                  26.6%                    29.8%                    11.5%                    11.1%           | 
|TERMINAL (d)       |                  12/40 (30%)              14/44 (32%)              5/40 (13%)               5/41 (12%)      | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.010N*                P=0.522                  P=0.052N                 P=0.046N*       | 
|POLY 3             |                  P=0.011N*                P=0.455                  P=0.060N                 P=0.051N        | 
|POLY 1.5           |                  P=0.011N*                P=0.438                  P=0.060N                 P=0.054N        | 
|POLY 6             |                  P=0.010N*                P=0.474                  P=0.057N                 P=0.048N*       | 
|LOGISTIC REGRESSION|                  P=0.010N*                P=0.522                  P=0.052N                 P=0.046N*       | 
|COCH-ARM / FISHERS |                  P=0.011N*                P=0.409                  P=0.053N                 P=0.053N        | 
|ORDER RESTRICTED   |                  P=0.026N*                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebrum                                                                                                                  | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  25/48 (52%)              18/48 (38%)              17/48 (35%)              17/48 (35%)     | 
|POLY-3 RATE (b)    |                  25/46.85                 18/46.99                 17/44.52                 17/45.38        | 
|POLY-3 PERCENT (g) |                  53.4%                    38.3%                    38.2%                    37.5%           | 
|TERMINAL (d)       |                  19/40 (48%)              17/44 (39%)              13/40 (33%)              15/41 (37%)     | 
|FIRST INCIDENCE    |                  562                      711                      568                      673             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.111N                 P=0.067N                 P=0.101N                 P=0.079N        | 
|POLY 3             |                  P=0.115N                 P=0.103N                 P=0.106N                 P=0.091N        | 
|POLY 1.5           |                  P=0.111N                 P=0.103N                 P=0.098N                 P=0.088N        | 
|POLY 6             |                  P=0.116N                 P=0.108N                 P=0.107N                 P=0.095N        | 
|LOGISTIC REGRESSION|                  P=0.102N                 P=0.102N                 P=0.088N                 P=0.078N        | 
|COCH-ARM / FISHERS |                  P=0.090N                 P=0.109N                 P=0.075N                 P=0.075N        | 
|ORDER RESTRICTED   |                  P=0.091N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland: Duct                                                                                                             | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  44/48 (92%)              47/47 (100%)             45/46 (98%)              44/44 (100%)    | 
|POLY-3 RATE (b)    |                  44/46.93                 47/47.00                 45/45.03                 44/44.00        | 
|POLY-3 PERCENT (g) |                  93.8%                    100.0%                   99.9%                    100.0%          | 
|TERMINAL (d)       |                  38/40 (95%)              43/43 (100%)             40/40 (100%)             39/39 (100%)    | 
|FIRST INCIDENCE    |                  562                      596                      442                      626             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.406                  P=0.594N                 P=0.482                  P=0.511         | 
|POLY 3             |                  P=0.051                  P=0.112                  P=0.124                  P=0.124         | 
|POLY 1.5           |                  P=0.039 *                P=0.088                  P=0.116                  P=0.099         | 
|POLY 6             |                  P=0.066                  P=0.138                  P=0.146                  P=0.150         | 
|LOGISTIC REGRESSION|                  P=0.034 *                P=0.131                  P=0.068                  P=0.148         | 
|COCH-ARM / FISHERS |                  P=0.050                  P=0.061                  P=0.194                  P=0.070         | 
|ORDER RESTRICTED   |                  P=0.007 **               (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Bilateral, Lens                                                                                                             | 
|     Cataract                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                2/48 (4%)                5/47 (11%)               2/48 (4%)       | 
|POLY-3 RATE (b)    |                  4/46.17                  2/47.38                  5/45.05                  2/45.08         | 
|POLY-3 PERCENT (g) |                  8.7%                     4.2%                     11.1%                    4.4%            | 
|TERMINAL (d)       |                  1/40 (3%)                1/44 (2%)                1/40 (3%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  562                      596                      444                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.390N                 P=0.317N                 P=0.488                  P=0.338N        | 
|POLY 3             |                  P=0.402N                 P=0.326N                 P=0.485                  P=0.348N        | 
|POLY 1.5           |                  P=0.399N                 P=0.330N                 P=0.482                  P=0.347N        | 
|POLY 6             |                  P=0.404N                 P=0.322N                 P=0.491                  P=0.349N        | 
|LOGISTIC REGRESSION|                  P=0.292N                 P=0.514N                 P=0.574                  P=0.315N        | 
|COCH-ARM / FISHERS |                  P=0.380N                 P=0.339N                 P=0.486                  P=0.339N        | 
|ORDER RESTRICTED   |                  P=0.345N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Lens                                                                                                                        | 
|     Cataract                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  5/48 (10%)               4/48 (8%)                6/47 (13%)               8/48 (17%)      | 
|POLY-3 RATE (b)    |                  5/46.17                  4/47.38                  6/45.05                  8/46.27         | 
|POLY-3 PERCENT (g) |                  10.8%                    8.4%                     13.3%                    17.3%           | 
|TERMINAL (d)       |                  2/40 (5%)                3/44 (7%)                2/40 (5%)                6/41 (15%)      | 
|FIRST INCIDENCE    |                  562                      596                      444                      161             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.154                  P=0.459N                 P=0.489                  P=0.292         | 
|POLY 3             |                  P=0.146                  P=0.484N                 P=0.483                  P=0.277         | 
|POLY 1.5           |                  P=0.147                  P=0.489N                 P=0.480                  P=0.276         | 
|POLY 6             |                  P=0.147                  P=0.479N                 P=0.489                  P=0.279         | 
|LOGISTIC REGRESSION|                  P=0.211                  P=0.640N                 P=0.555                  P=0.319         | 
|COCH-ARM / FISHERS |                  P=0.150                  P=0.500N                 P=0.485                  P=0.276         | 
|ORDER RESTRICTED   |                  P=0.209                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                5/48 (10%)               5/48 (10%)               4/48 (8%)       | 
|POLY-3 RATE (b)    |                  4/45.14                  5/46.93                  5/43.58                  4/45.08         | 
|POLY-3 PERCENT (g) |                  8.9%                     10.7%                    11.5%                    8.9%            | 
|TERMINAL (d)       |                  4/40 (10%)               5/44 (11%)               5/40 (13%)               4/41 (10%)      | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.537N                 P=0.560                  P=0.500                  P=0.631N        | 
|POLY 3             |                  P=0.542N                 P=0.524                  P=0.478                  P=0.642         | 
|POLY 1.5           |                  P=0.544N                 P=0.515                  P=0.480                  P=0.638         | 
|POLY 6             |                  P=0.535N                 P=0.535                  P=0.483                  P=0.636N        | 
|LOGISTIC REGRESSION|                  P=0.537N                 P=0.560                  P=0.500                  P=0.631N        | 
|COCH-ARM / FISHERS |                  P=0.529N                 P=0.500                  P=0.500                  P=0.643N        | 
|ORDER RESTRICTED   |                  P=0.635                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                0/48 (0%)                2/48 (4%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  0/46.93                  2/43.79                  0/45.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     4.6%                     0.0%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/44 (0%)                0/40 (0%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      694                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.586                  (e)                      P=0.245                  (e)             | 
|POLY 3             |                  P=0.580                  (e)                      P=0.230                  (e)             | 
|POLY 1.5           |                  P=0.577                  (e)                      P=0.231                  (e)             | 
|POLY 6             |                  P=0.584                  (e)                      P=0.233                  (e)             | 
|LOGISTIC REGRESSION|                  P=0.586                  (e)                      P=0.235                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.584                  (e)                      P=0.247                  (e)             | 
|ORDER RESTRICTED   |                  P=0.241                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                7/47 (15%)               3/48 (6%)                2/47 (4%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  7/46.38                  3/43.66                  2/45.07         | 
|POLY-3 PERCENT (g) |                  4.4%                     15.1%                    6.9%                     4.4%            | 
|TERMINAL (d)       |                  2/40 (5%)                7/44 (16%)               2/40 (5%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  707                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.300N                 P=0.105                  P=0.502                  P=0.686N        | 
|POLY 3             |                  P=0.294N                 P=0.085                  P=0.485                  P=0.693         | 
|POLY 1.5           |                  P=0.299N                 P=0.081                  P=0.486                  P=0.690         | 
|POLY 6             |                  P=0.286N                 P=0.091                  P=0.489                  P=0.689N        | 
|LOGISTIC REGRESSION|                  P=0.294N                 P=0.105                  P=0.490                  P=0.686N        | 
|COCH-ARM / FISHERS |                  P=0.302N                 P=0.074                  P=0.500                  P=0.684         | 
|ORDER RESTRICTED   |                  P=0.267N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Glomerulus                                                                                                               | 
|     Amyloid Deposition                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                0/47 (0%)                0/48 (0%)                2/47 (4%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  0/46.38                  0/43.58                  2/45.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     0.0%                     4.4%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/44 (0%)                0/40 (0%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      ---                      723             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.046 *                (e)                      (e)                      P=0.248         | 
|POLY 3             |                  P=0.043 *                (e)                      (e)                      P=0.237         | 
|POLY 1.5           |                  P=0.043 *                (e)                      (e)                      P=0.235         | 
|POLY 6             |                  P=0.043 *                (e)                      (e)                      P=0.240         | 
|LOGISTIC REGRESSION|                  P=0.045 *                (e)                      (e)                      P=0.244         | 
|COCH-ARM / FISHERS |                  P=0.044 *                (e)                      (e)                      P=0.242         | 
|ORDER RESTRICTED   |                  P=0.029 *                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Pelvis                                                                                                                   | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                0/47 (0%)                0/48 (0%)                0/47 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.43                  0/46.38                  0/43.58                  0/45.07         | 
|POLY-3 PERCENT (g) |                  4.4%                     0.0%                     0.0%                     0.0%            | 
|TERMINAL (d)       |                  1/40 (3%)                0/44 (0%)                0/40 (0%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  647                      ---                      ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.126N                 P=0.227N                 P=0.245N                 P=0.239N        | 
|POLY 3             |                  P=0.128N                 P=0.233N                 P=0.247N                 P=0.239N        | 
|POLY 1.5           |                  P=0.126N                 P=0.236N                 P=0.245N                 P=0.241N        | 
|POLY 6             |                  P=0.130N                 P=0.229N                 P=0.246N                 P=0.237N        | 
|LOGISTIC REGRESSION|                  P=0.119N                 P=0.278N                 P=0.229N                 P=0.244N        | 
|COCH-ARM / FISHERS |                  P=0.123N                 P=0.253N                 P=0.247N                 P=0.253N        | 
|ORDER RESTRICTED   |                  P=0.030N*                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Accumulation, Hyaline Droplet                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                0/47 (0%)                1/48 (2%)                1/47 (2%)       | 
|POLY-3 RATE (b)    |                  4/46.30                  0/46.38                  1/43.79                  1/45.07         | 
|POLY-3 PERCENT (g) |                  8.6%                     0.0%                     2.3%                     2.2%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/44 (0%)                0/40 (0%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  562                      ---                      673                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.185N                 P=0.061N                 P=0.194N                 P=0.184N        | 
|POLY 3             |                  P=0.187N                 P=0.060N                 P=0.196N                 P=0.187N        | 
|POLY 1.5           |                  P=0.185N                 P=0.061N                 P=0.192N                 P=0.187N        | 
|POLY 6             |                  P=0.188N                 P=0.059N                 P=0.198N                 P=0.188N        | 
|LOGISTIC REGRESSION|                  P=0.161N                 P=0.125N                 P=0.133N                 P=0.183N        | 
|COCH-ARM / FISHERS |                  P=0.180N                 P=0.061N                 P=0.181N                 P=0.187N        | 
|ORDER RESTRICTED   |                  P=0.036N*                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  1/48 (2%)                1/48 (2%)                3/46 (7%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  1/45.14                  1/46.93                  3/43.32                  0/45.08         | 
|POLY-3 PERCENT (g) |                  2.2%                     2.1%                     6.9%                     0.0%            | 
|TERMINAL (d)       |                  1/40 (3%)                1/44 (2%)                3/40 (8%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.417N                 P=0.740N                 P=0.305                  P=0.495N        | 
|POLY 3             |                  P=0.422N                 P=0.752N                 P=0.291                  P=0.500N        | 
|POLY 1.5           |                  P=0.424N                 P=0.755N                 P=0.289                  P=0.502N        | 
|POLY 6             |                  P=0.418N                 P=0.748N                 P=0.295                  P=0.498N        | 
|LOGISTIC REGRESSION|                  P=0.417N                 P=0.740N                 P=0.305                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.415N                 P=0.753N                 P=0.292                  P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.224N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                1/48 (2%)                0/46 (0%)                2/48 (4%)       | 
|POLY-3 RATE (b)    |                  2/45.43                  1/46.93                  0/43.32                  2/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     2.1%                     0.0%                     4.4%            | 
|TERMINAL (d)       |                  1/40 (3%)                1/44 (2%)                0/40 (0%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  647                      727 (T)                  ---                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.581                  P=0.475N                 P=0.245N                 P=0.689N        | 
|POLY 3             |                  P=0.577                  P=0.489N                 P=0.248N                 P=0.691         | 
|POLY 1.5           |                  P=0.578                  P=0.493N                 P=0.249N                 P=0.689         | 
|POLY 6             |                  P=0.578                  P=0.485N                 P=0.246N                 P=0.693N        | 
|LOGISTIC REGRESSION|                  P=0.583                  P=0.531N                 P=0.240N                 P=0.694         | 
|COCH-ARM / FISHERS |                  P=0.585                  P=0.500N                 P=0.258N                 P=0.692N        | 
|ORDER RESTRICTED   |                  P=0.411                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                6/48 (13%)               8/46 (17%)               12/48 (25%)     | 
|POLY-3 RATE (b)    |                  4/45.14                  6/46.93                  8/43.40                  12/45.73        | 
|POLY-3 PERCENT (g) |                  8.9%                     12.8%                    18.4%                    26.2%           | 
|TERMINAL (d)       |                  4/40 (10%)               6/44 (14%)               7/40 (18%)               8/41 (20%)      | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  707                      633             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.014 *                P=0.430                  P=0.179                  P=0.036 *       | 
|POLY 3             |                  P=0.012 *                P=0.394                  P=0.157                  P=0.027 *       | 
|POLY 1.5           |                  P=0.012 *                P=0.385                  P=0.155                  P=0.025 *       | 
|POLY 6             |                  P=0.014 *                P=0.405                  P=0.164                  P=0.030 *       | 
|LOGISTIC REGRESSION|                  P=0.012 *                P=0.430                  P=0.172                  P=0.027 *       | 
|COCH-ARM / FISHERS |                  P=0.013 *                P=0.370                  P=0.157                  P=0.026 *       | 
|ORDER RESTRICTED   |                  P=0.016 *                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  5/48 (10%)               9/48 (19%)               8/46 (17%)               4/48 (8%)       | 
|POLY-3 RATE (b)    |                  5/45.14                  9/46.93                  8/43.32                  4/45.08         | 
|POLY-3 PERCENT (g) |                  11.1%                    19.2%                    18.5%                    8.9%            | 
|TERMINAL (d)       |                  5/40 (13%)               9/44 (21%)               8/40 (20%)               4/41 (10%)      | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.302N                 P=0.248                  P=0.273                  P=0.484N        | 
|POLY 3             |                  P=0.309N                 P=0.215                  P=0.249                  P=0.501N        | 
|POLY 1.5           |                  P=0.314N                 P=0.207                  P=0.245                  P=0.506N        | 
|POLY 6             |                  P=0.300N                 P=0.224                  P=0.256                  P=0.492N        | 
|LOGISTIC REGRESSION|                  P=0.302N                 P=0.248                  P=0.273                  P=0.484N        | 
|COCH-ARM / FISHERS |                  P=0.301N                 P=0.193                  P=0.249                  P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.253N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                0/48 (0%)                0/46 (0%)                2/48 (4%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  0/46.93                  0/43.32                  2/45.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     0.0%                     4.4%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/44 (0%)                0/40 (0%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      ---                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.044 *                (e)                      (e)                      P=0.244         | 
|POLY 3             |                  P=0.044 *                (e)                      (e)                      P=0.237         | 
|POLY 1.5           |                  P=0.044 *                (e)                      (e)                      P=0.235         | 
|POLY 6             |                  P=0.044 *                (e)                      (e)                      P=0.240         | 
|LOGISTIC REGRESSION|                  (e)                      (e)                      (e)                      P=0.244         | 
|COCH-ARM / FISHERS |                  P=0.046 *                (e)                      (e)                      P=0.247         | 
|ORDER RESTRICTED   |                  P=0.029 *                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Tension Lipidosis                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  10/48 (21%)              7/48 (15%)               8/46 (17%)               6/48 (13%)      | 
|POLY-3 RATE (b)    |                  10/45.14                 7/46.93                  8/43.84                  6/45.09         | 
|POLY-3 PERCENT (g) |                  22.2%                    14.9%                    18.3%                    13.3%           | 
|TERMINAL (d)       |                  10/40 (25%)              7/44 (16%)               7/40 (18%)               5/41 (12%)      | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  568                      723             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.216N                 P=0.224N                 P=0.399N                 P=0.190N        | 
|POLY 3             |                  P=0.225N                 P=0.266N                 P=0.423N                 P=0.205N        | 
|POLY 1.5           |                  P=0.227N                 P=0.278N                 P=0.434N                 P=0.211N        | 
|POLY 6             |                  P=0.219N                 P=0.254N                 P=0.405N                 P=0.196N        | 
|LOGISTIC REGRESSION|                  P=0.219N                 P=0.224N                 P=0.435N                 P=0.175N        | 
|COCH-ARM / FISHERS |                  P=0.213N                 P=0.297N                 P=0.436N                 P=0.206N        | 
|ORDER RESTRICTED   |                  P=0.210N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                3/48 (6%)                2/48 (4%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  3/46.93                  2/43.58                  0/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     6.4%                     4.6%                     0.0%            | 
|TERMINAL (d)       |                  2/40 (5%)                3/44 (7%)                2/40 (5%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.130N                 P=0.544                  P=0.695                  P=0.233N        | 
|POLY 3             |                  P=0.132N                 P=0.518                  P=0.681                  P=0.237N        | 
|POLY 1.5           |                  P=0.134N                 P=0.511                  P=0.682                  P=0.239N        | 
|POLY 6             |                  P=0.130N                 P=0.525                  P=0.684                  P=0.234N        | 
|LOGISTIC REGRESSION|                  P=0.130N                 P=0.544                  P=0.695                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.129N                 P=0.500                  P=0.692N                 P=0.247N        | 
|ORDER RESTRICTED   |                  P=0.142N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  6/48 (13%)               6/48 (13%)               6/48 (13%)               2/48 (4%)       | 
|POLY-3 RATE (b)    |                  6/45.27                  6/46.93                  6/44.36                  2/45.08         | 
|POLY-3 PERCENT (g) |                  13.3%                    12.8%                    13.5%                    4.4%            | 
|TERMINAL (d)       |                  5/40 (13%)               6/44 (14%)               5/40 (13%)               2/41 (5%)       | 
|FIRST INCIDENCE    |                  694                      727 (T)                  442                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.104N                 P=0.552N                 P=0.619N                 P=0.128N        | 
|POLY 3             |                  P=0.106N                 P=0.595N                 P=0.606                  P=0.134N        | 
|POLY 1.5           |                  P=0.107N                 P=0.604N                 P=0.605                  P=0.136N        | 
|POLY 6             |                  P=0.103N                 P=0.585N                 P=0.614                  P=0.130N        | 
|LOGISTIC REGRESSION|                  P=0.103N                 P=0.573N                 P=0.619                  P=0.128N        | 
|COCH-ARM / FISHERS |                  P=0.100N                 P=0.621N                 P=0.621N                 P=0.134N        | 
|ORDER RESTRICTED   |                  P=0.142N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Proteinosis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                0/48 (0%)                0/48 (0%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  0/46.93                  0/43.58                  0/45.08         | 
|POLY-3 PERCENT (g) |                  6.7%                     0.0%                     0.0%                     0.0%            | 
|TERMINAL (d)       |                  3/40 (8%)                0/44 (0%)                0/40 (0%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  ---                      ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.053N                 P=0.105N                 P=0.121N                 P=0.117N        | 
|POLY 3             |                  P=0.053N                 P=0.112N                 P=0.125N                 P=0.119N        | 
|POLY 1.5           |                  P=0.052N                 P=0.114N                 P=0.125N                 P=0.120N        | 
|POLY 6             |                  P=0.054N                 P=0.109N                 P=0.123N                 P=0.116N        | 
|LOGISTIC REGRESSION|                  P=0.053N                 (e)                      (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.052N                 P=0.121N                 P=0.121N                 P=0.121N        | 
|ORDER RESTRICTED   |                  P=0.008N**               (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  1/48 (2%)                3/48 (6%)                0/48 (0%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  1/45.14                  3/46.93                  0/43.58                  1/45.08         | 
|POLY-3 PERCENT (g) |                  2.2%                     6.4%                     0.0%                     2.2%            | 
|TERMINAL (d)       |                  1/40 (3%)                3/44 (7%)                0/40 (0%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  ---                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.391N                 P=0.340                  P=0.500N                 P=0.756N        | 
|POLY 3             |                  P=0.390N                 P=0.320                  P=0.507N                 P=0.760         | 
|POLY 1.5           |                  P=0.391N                 P=0.314                  P=0.506N                 P=0.758         | 
|POLY 6             |                  P=0.385N                 P=0.326                  P=0.505N                 P=0.758N        | 
|LOGISTIC REGRESSION|                  P=0.391N                 P=0.340                  (e)                      P=0.756N        | 
|COCH-ARM / FISHERS |                  P=0.387N                 P=0.308                  P=0.500N                 P=0.753N        | 
|ORDER RESTRICTED   |                  P=0.280N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                1/48 (2%)                2/47 (4%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  1/46.93                  2/42.71                  1/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     2.1%                     4.7%                     2.2%            | 
|TERMINAL (d)       |                  2/40 (5%)                1/44 (2%)                2/40 (5%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.455N                 P=0.467N                 P=0.695                  P=0.491N        | 
|POLY 3             |                  P=0.462N                 P=0.486N                 P=0.674                  P=0.500N        | 
|POLY 1.5           |                  P=0.462N                 P=0.491N                 P=0.675                  P=0.503N        | 
|POLY 6             |                  P=0.460N                 P=0.481N                 P=0.678                  P=0.496N        | 
|LOGISTIC REGRESSION|                  P=0.455N                 P=0.467N                 P=0.695                  P=0.491N        | 
|COCH-ARM / FISHERS |                  P=0.452N                 P=0.500N                 P=0.684                  P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.444N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  8/45 (18%)               8/46 (17%)               5/44 (11%)               5/46 (11%)      | 
|POLY-3 RATE (b)    |                  8/43.54                  8/45.23                  5/41.45                  5/44.16         | 
|POLY-3 PERCENT (g) |                  18.4%                    17.7%                    12.1%                    11.3%           | 
|TERMINAL (d)       |                  8/39 (21%)               7/42 (17%)               5/39 (13%)               4/40 (10%)      | 
|FIRST INCIDENCE    |                  727 (T)                  644                      727 (T)                  704             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.174N                 P=0.546N                 P=0.273N                 P=0.258N        | 
|POLY 3             |                  P=0.177N                 P=0.575N                 P=0.307N                 P=0.266N        | 
|POLY 1.5           |                  P=0.176N                 P=0.582N                 P=0.306N                 P=0.267N        | 
|POLY 6             |                  P=0.174N                 P=0.564N                 P=0.302N                 P=0.260N        | 
|LOGISTIC REGRESSION|                  P=0.174N                 P=0.581N                 P=0.273N                 P=0.252N        | 
|COCH-ARM / FISHERS |                  P=0.167N                 P=0.589N                 P=0.290N                 P=0.261N        | 
|ORDER RESTRICTED   |                  P=0.282N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Lumbar                                                                                                               | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/13 (31%)               4/13 (31%)               2/6 (33%)                1/9 (11%)       | 
|POLY-3 RATE (b)    |                  4/12.47                  4/12.23                  2/5.58                   1/6.87          | 
|POLY-3 PERCENT (g) |                  32.1%                    32.7%                    35.8%                    14.6%           | 
|TERMINAL (d)       |                  4/10 (40%)               4/10 (40%)               2/3 (67%)                1/5 (20%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.379N                 P=0.672                  P=0.442                  P=0.426N        | 
|POLY 3             |                  P=0.314N                 P=0.650                  P=0.643                  P=0.389N        | 
|POLY 1.5           |                  P=0.298N                 P=0.653                  P=0.649                  P=0.372N        | 
|POLY 6             |                  P=0.316N                 P=0.648                  P=0.631                  P=0.389N        | 
|LOGISTIC REGRESSION|                  P=0.379N                 P=0.672                  P=0.442                  P=0.426N        | 
|COCH-ARM / FISHERS |                  P=0.210N                 P=0.664N                 P=0.652                  P=0.293N        | 
|ORDER RESTRICTED   |                  P=0.346N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/13 (0%)                2/13 (15%)               0/6 (0%)                 0/9 (0%)        | 
|POLY-3 RATE (b)    |                  0/12.47                  2/12.23                  0/5.58                   0/6.87          | 
|POLY-3 PERCENT (g) |                  0.0%                     16.4%                    0.0%                     0.0%            | 
|TERMINAL (d)       |                  0/10 (0%)                2/10 (20%)               0/3 (0%)                 0/5 (0%)        | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.558N                 P=0.234                  (e)                      (e)             | 
|POLY 3             |                  P=0.515N                 P=0.225                  (e)                      (e)             | 
|POLY 1.5           |                  P=0.507N                 P=0.227                  (e)                      (e)             | 
|POLY 6             |                  P=0.521N                 P=0.223                  (e)                      (e)             | 
|LOGISTIC REGRESSION|                  (e)                      P=0.234                  (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.475N                 P=0.240                  (e)                      (e)             | 
|ORDER RESTRICTED   |                  P=0.374                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Renal                                                                                                                | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/13 (15%)               1/13 (8%)                2/6 (33%)                1/9 (11%)       | 
|POLY-3 RATE (b)    |                  2/12.47                  1/12.23                  2/5.58                   1/6.87          | 
|POLY-3 PERCENT (g) |                  16.0%                    8.2%                     35.8%                    14.6%           | 
|TERMINAL (d)       |                  2/10 (20%)               1/10 (10%)               2/3 (67%)                1/5 (20%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.448                  P=0.500N                 P=0.215                  P=0.746         | 
|POLY 3             |                  P=0.474                  P=0.507N                 P=0.377                  P=0.701N        | 
|POLY 1.5           |                  P=0.492                  P=0.504N                 P=0.384                  P=0.690N        | 
|POLY 6             |                  P=0.474                  P=0.509N                 P=0.365                  P=0.703N        | 
|LOGISTIC REGRESSION|                  P=0.448                  P=0.500N                 P=0.215                  P=0.746         | 
|COCH-ARM / FISHERS |                  P=0.596                  P=0.500N                 P=0.373                  P=0.642N        | 
|ORDER RESTRICTED   |                  P=0.419                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/2 (100%)               3/5 (60%)                1/1 (100%)               0/0 (0%)        | 
|POLY-3 RATE (b)    |                  2/2.00                   3/5.00                   1/1.00                   0/0.00          | 
|POLY-3 PERCENT (g) |                  100.0%                   60.0%                    100.0%                   0.0%            | 
|TERMINAL (d)       |                  2/2 (100%)               3/5 (60%)                1/1 (100%)               0/0 (0%)        | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.861N                 P=0.451N                 (e)                      (e)             | 
|POLY 3             |                  (e)                      P=0.451N                 (e)                      (e)             | 
|POLY 1.5           |                  (e)                      P=0.451N                 (e)                      (e)             | 
|POLY 6             |                  (e)                      P=0.451N                 (e)                      (e)             | 
|LOGISTIC REGRESSION|                  P=0.861N                 P=0.451N                 (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.877N                 P=0.476N                 (e)                      (e)             | 
|ORDER RESTRICTED   |                  (e)                      (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  28/48 (58%)              33/46 (72%)              36/46 (78%)              36/45 (80%)     | 
|POLY-3 RATE (b)    |                  28/45.53                 33/45.38                 36/43.73                 36/43.42        | 
|POLY-3 PERCENT (g) |                  61.5%                    72.7%                    82.3%                    82.9%           | 
|TERMINAL (d)       |                  26/40 (65%)              33/43 (77%)              33/40 (83%)              34/39 (87%)     | 
|FIRST INCIDENCE    |                  676                      727 (T)                  673                      633             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.015 *                P=0.339                  P=0.061                  P=0.036 *       | 
|POLY 3             |                  P=0.012 *                P=0.176                  P=0.021 *                P=0.018 *       | 
|POLY 1.5           |                  P=0.012 *                P=0.157                  P=0.021 *                P=0.017 *       | 
|POLY 6             |                  P=0.012 *                P=0.198                  P=0.025 *                P=0.020 *       | 
|LOGISTIC REGRESSION|                  P=0.014 *                P=0.286                  P=0.031 *                P=0.028 *       | 
|COCH-ARM / FISHERS |                  P=0.017 *                P=0.126                  P=0.032 *                P=0.021 *       | 
|ORDER RESTRICTED   |                  P=0.011 *                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  19/48 (40%)              21/46 (46%)              14/46 (30%)              13/45 (29%)     | 
|POLY-3 RATE (b)    |                  19/45.91                 21/45.70                 14/43.32                 13/43.50        | 
|POLY-3 PERCENT (g) |                  41.4%                    46.0%                    32.3%                    29.9%           | 
|TERMINAL (d)       |                  16/40 (40%)              19/43 (44%)              14/40 (35%)              11/39 (28%)     | 
|FIRST INCIDENCE    |                  599                      659                      727 (T)                  633             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.080N                 P=0.534                  P=0.199N                 P=0.163N        | 
|POLY 3             |                  P=0.080N                 P=0.410                  P=0.252N                 P=0.180N        | 
|POLY 1.5           |                  P=0.082N                 P=0.388                  P=0.252N                 P=0.187N        | 
|POLY 6             |                  P=0.077N                 P=0.434                  P=0.250N                 P=0.171N        | 
|LOGISTIC REGRESSION|                  P=0.079N                 P=0.401                  P=0.229N                 P=0.183N        | 
|COCH-ARM / FISHERS |                  P=0.081N                 P=0.350                  P=0.238N                 P=0.193N        | 
|ORDER RESTRICTED   |                  P=0.137N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                0/46 (0%)                1/46 (2%)                1/45 (2%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  0/45.38                  1/43.32                  1/43.07         | 
|POLY-3 PERCENT (g) |                  6.7%                     0.0%                     2.3%                     2.3%            | 
|TERMINAL (d)       |                  3/40 (8%)                0/43 (0%)                1/40 (3%)                1/39 (3%)       | 
|FIRST INCIDENCE    |                  727 (T)                  ---                      727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.327N                 P=0.109N                 P=0.305N                 P=0.314N        | 
|POLY 3             |                  P=0.338N                 P=0.118N                 P=0.320N                 P=0.322N        | 
|POLY 1.5           |                  P=0.335N                 P=0.121N                 P=0.322N                 P=0.326N        | 
|POLY 6             |                  P=0.340N                 P=0.114N                 P=0.315N                 P=0.317N        | 
|LOGISTIC REGRESSION|                  P=0.327N                 (e)                      P=0.305N                 P=0.314N        | 
|COCH-ARM / FISHERS |                  P=0.329N                 P=0.129N                 P=0.325N                 P=0.333N        | 
|ORDER RESTRICTED   |                  P=0.111N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary: Bilateral                                                                                                                 | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/48 (8%)                3/46 (7%)                3/46 (7%)                2/45 (4%)       | 
|POLY-3 RATE (b)    |                  4/45.91                  3/45.38                  3/43.32                  2/43.07         | 
|POLY-3 PERCENT (g) |                  8.7%                     6.6%                     6.9%                     4.6%            | 
|TERMINAL (d)       |                  1/40 (3%)                3/43 (7%)                3/40 (8%)                2/39 (5%)       | 
|FIRST INCIDENCE    |                  599                      727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.294N                 P=0.466N                 P=0.505N                 P=0.343N        | 
|POLY 3             |                  P=0.307N                 P=0.506N                 P=0.532N                 P=0.367N        | 
|POLY 1.5           |                  P=0.306N                 P=0.512N                 P=0.531N                 P=0.368N        | 
|POLY 6             |                  P=0.308N                 P=0.501N                 P=0.531N                 P=0.366N        | 
|LOGISTIC REGRESSION|                  P=0.298N                 P=0.602N                 P=0.518N                 P=0.370N        | 
|COCH-ARM / FISHERS |                  P=0.299N                 P=0.524N                 P=0.524N                 P=0.370N        | 
|ORDER RESTRICTED   |                  P=0.356N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary: Germinal Epithelium                                                                                                       | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                0/46 (0%)                2/46 (4%)                0/45 (0%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  0/45.38                  2/43.32                  0/43.07         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     4.6%                     0.0%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/43 (0%)                2/40 (5%)                0/39 (0%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.573                  (e)                      P=0.238                  (e)             | 
|POLY 3             |                  P=0.576                  (e)                      P=0.228                  (e)             | 
|POLY 1.5           |                  P=0.574                  (e)                      P=0.227                  (e)             | 
|POLY 6             |                  P=0.579                  (e)                      P=0.231                  (e)             | 
|LOGISTIC REGRESSION|                  (e)                      (e)                      P=0.238                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.572                  (e)                      P=0.237                  (e)             | 
|ORDER RESTRICTED   |                  P=0.239                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  6/47 (13%)               4/47 (9%)                2/44 (5%)                3/47 (6%)       | 
|POLY-3 RATE (b)    |                  6/45.00                  4/46.38                  2/41.53                  3/45.07         | 
|POLY-3 PERCENT (g) |                  13.3%                    8.6%                     4.8%                     6.7%            | 
|TERMINAL (d)       |                  6/40 (15%)               4/44 (9%)                2/40 (5%)                3/41 (7%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.173N                 P=0.310N                 P=0.133N                 P=0.229N        | 
|POLY 3             |                  P=0.182N                 P=0.351N                 P=0.160N                 P=0.241N        | 
|POLY 1.5           |                  P=0.181N                 P=0.359N                 P=0.161N                 P=0.244N        | 
|POLY 6             |                  P=0.180N                 P=0.339N                 P=0.154N                 P=0.235N        | 
|LOGISTIC REGRESSION|                  P=0.173N                 P=0.310N                 P=0.133N                 P=0.229N        | 
|COCH-ARM / FISHERS |                  P=0.176N                 P=0.370N                 P=0.156N                 P=0.243N        | 
|ORDER RESTRICTED   |                  P=0.151N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/47 (4%)                0/47 (0%)                0/44 (0%)                0/47 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.00                  0/46.38                  0/41.53                  0/45.07         | 
|POLY-3 PERCENT (g) |                  4.4%                     0.0%                     0.0%                     0.0%            | 
|TERMINAL (d)       |                  2/40 (5%)                0/44 (0%)                0/40 (0%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  ---                      ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.123N                 P=0.218N                 P=0.238N                 P=0.233N        | 
|POLY 3             |                  P=0.127N                 P=0.231N                 P=0.255N                 P=0.237N        | 
|POLY 1.5           |                  P=0.126N                 P=0.234N                 P=0.256N                 P=0.238N        | 
|POLY 6             |                  P=0.129N                 P=0.226N                 P=0.252N                 P=0.234N        | 
|LOGISTIC REGRESSION|                  P=0.123N                 (e)                      (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.125N                 P=0.247N                 P=0.264N                 P=0.247N        | 
|ORDER RESTRICTED   |                  P=0.029N*                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  1/48 (2%)                2/47 (4%)                5/46 (11%)               0/45 (0%)       | 
|POLY-3 RATE (b)    |                  1/45.35                  2/45.93                  5/41.58                  0/42.08         | 
|POLY-3 PERCENT (g) |                  2.2%                     4.4%                     12.0%                    0.0%            | 
|TERMINAL (d)       |                  0/40 (0%)                2/43 (5%)                5/38 (13%)               0/38 (0%)       | 
|FIRST INCIDENCE    |                  673                      727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.437N                 P=0.519                  P=0.095                  P=0.500N        | 
|POLY 3             |                  P=0.442N                 P=0.504                  P=0.082                  P=0.515N        | 
|POLY 1.5           |                  P=0.443N                 P=0.500                  P=0.084                  P=0.516N        | 
|POLY 6             |                  P=0.438N                 P=0.509                  P=0.083                  P=0.513N        | 
|LOGISTIC REGRESSION|                  P=0.440N                 P=0.481                  P=0.086                  P=0.501N        | 
|COCH-ARM / FISHERS |                  P=0.431N                 P=0.492                  P=0.092                  P=0.516N        | 
|ORDER RESTRICTED   |                  P=0.135N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands: Parotid Gland                                                                                                   | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  5/48 (10%)               12/48 (25%)              4/48 (8%)                5/48 (10%)      | 
|POLY-3 RATE (b)    |                  5/45.43                  12/46.93                 4/44.36                  5/45.08         | 
|POLY-3 PERCENT (g) |                  11.0%                    25.6%                    9.0%                     11.1%           | 
|TERMINAL (d)       |                  4/40 (10%)               12/44 (27%)              3/40 (8%)                5/41 (12%)      | 
|FIRST INCIDENCE    |                  647                      727 (T)                  442                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.244N                 P=0.082                  P=0.505N                 P=0.617N        | 
|POLY 3             |                  P=0.242N                 P=0.060                  P=0.515N                 P=0.625         | 
|POLY 1.5           |                  P=0.245N                 P=0.058                  P=0.515N                 P=0.622         | 
|POLY 6             |                  P=0.236N                 P=0.063                  P=0.510N                 P=0.630N        | 
|LOGISTIC REGRESSION|                  P=0.244N                 P=0.067                  P=0.481N                 P=0.631N        | 
|COCH-ARM / FISHERS |                  P=0.235N                 P=0.053                  P=0.500N                 P=0.630N        | 
|ORDER RESTRICTED   |                  P=0.198N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands: Submandibular Gland                                                                                             | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  35/48 (73%)              28/48 (58%)              28/48 (58%)              28/48 (58%)     | 
|POLY-3 RATE (b)    |                  35/46.41                 28/46.93                 28/44.44                 28/45.89        | 
|POLY-3 PERCENT (g) |                  75.4%                    59.7%                    63.0%                    61.0%           | 
|TERMINAL (d)       |                  32/40 (80%)              28/44 (64%)              26/40 (65%)              24/41 (59%)     | 
|FIRST INCIDENCE    |                  562                      727 (T)                  442                      626             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.154N                 P=0.024N*                P=0.099N                 P=0.087N        | 
|POLY 3             |                  P=0.157N                 P=0.076N                 P=0.142N                 P=0.101N        | 
|POLY 1.5           |                  P=0.163N                 P=0.082N                 P=0.133N                 P=0.108N        | 
|POLY 6             |                  P=0.138N                 P=0.072N                 P=0.140N                 P=0.085N        | 
|LOGISTIC REGRESSION|                  P=0.164N                 P=0.053N                 P=0.140N                 P=0.102N        | 
|COCH-ARM / FISHERS |                  P=0.136N                 P=0.098N                 P=0.098N                 P=0.098N        | 
|ORDER RESTRICTED   |                  P=0.108N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spinal Cord: Thoracic, Axon                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  13/48 (27%)              14/48 (29%)              19/48 (40%)              19/48 (40%)     | 
|POLY-3 RATE (b)    |                  13/45.46                 14/47.49                 19/43.66                 19/45.09        | 
|POLY-3 PERCENT (g) |                  28.6%                    29.5%                    43.5%                    42.1%           | 
|TERMINAL (d)       |                  11/40 (28%)              12/44 (27%)              18/40 (45%)              18/41 (44%)     | 
|FIRST INCIDENCE    |                  676                      644                      707                      723             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.080                  P=0.569N                 P=0.142                  P=0.163         | 
|POLY 3             |                  P=0.064                  P=0.553                  P=0.105                  P=0.128         | 
|POLY 1.5           |                  P=0.066                  P=0.533                  P=0.110                  P=0.127         | 
|POLY 6             |                  P=0.063                  P=0.576                  P=0.106                  P=0.133         | 
|LOGISTIC REGRESSION|                  P=0.074                  P=0.530                  P=0.119                  P=0.153         | 
|COCH-ARM / FISHERS |                  P=0.084                  P=0.500                  P=0.139                  P=0.139         | 
|ORDER RESTRICTED   |                  P=0.120                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  9/47 (19%)               8/47 (17%)               3/45 (7%)                5/47 (11%)      | 
|POLY-3 RATE (b)    |                  9/45.00                  8/46.63                  3/42.45                  5/45.18         | 
|POLY-3 PERCENT (g) |                  20.0%                    17.2%                    7.1%                     11.1%           | 
|TERMINAL (d)       |                  7/40 (18%)               7/44 (16%)               3/40 (8%)                3/41 (7%)       | 
|FIRST INCIDENCE    |                  676                      659                      727 (T)                  704             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.107N                 P=0.422N                 P=0.065N                 P=0.186N        | 
|POLY 3             |                  P=0.106N                 P=0.468N                 P=0.073N                 P=0.190N        | 
|POLY 1.5           |                  P=0.105N                 P=0.480N                 P=0.073N                 P=0.192N        | 
|POLY 6             |                  P=0.106N                 P=0.455N                 P=0.071N                 P=0.187N        | 
|LOGISTIC REGRESSION|                  P=0.104N                 P=0.495N                 P=0.072N                 P=0.188N        | 
|COCH-ARM / FISHERS |                  P=0.102N                 P=0.500N                 P=0.070N                 P=0.193N        | 
|ORDER RESTRICTED   |                  P=0.102N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  6/47 (13%)               6/47 (13%)               7/45 (16%)               2/47 (4%)       | 
|POLY-3 RATE (b)    |                  6/44.68                  6/46.38                  7/42.45                  2/45.07         | 
|POLY-3 PERCENT (g) |                  13.4%                    12.9%                    16.5%                    4.4%            | 
|TERMINAL (d)       |                  6/40 (15%)               6/44 (14%)               7/40 (18%)               2/41 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.114N                 P=0.553N                 P=0.500                  P=0.126N        | 
|POLY 3             |                  P=0.116N                 P=0.594N                 P=0.460                  P=0.130N        | 
|POLY 1.5           |                  P=0.117N                 P=0.604N                 P=0.458                  P=0.132N        | 
|POLY 6             |                  P=0.115N                 P=0.582N                 P=0.468                  P=0.127N        | 
|LOGISTIC REGRESSION|                  P=0.114N                 P=0.553N                 P=0.500                  P=0.126N        | 
|COCH-ARM / FISHERS |                  P=0.115N                 P=0.621N                 P=0.466                  P=0.134N        | 
|ORDER RESTRICTED   |                  P=0.113N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 23      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/47 (4%)                3/47 (6%)                2/46 (4%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  2/45.00                  3/46.38                  2/43.32                  1/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     6.5%                     4.6%                     2.2%            | 
|TERMINAL (d)       |                  2/40 (5%)                3/44 (7%)                2/40 (5%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.308N                 P=0.544                  P=0.695                  P=0.491N        | 
|POLY 3             |                  P=0.311N                 P=0.514                  P=0.680                  P=0.499N        | 
|POLY 1.5           |                  P=0.311N                 P=0.508                  P=0.680                  P=0.500N        | 
|POLY 6             |                  P=0.308N                 P=0.522                  P=0.684                  P=0.495N        | 
|LOGISTIC REGRESSION|                  P=0.308N                 P=0.544                  P=0.695                  P=0.491N        | 
|COCH-ARM / FISHERS |                  P=0.299N                 P=0.500                  P=0.683                  P=0.492N        | 
|ORDER RESTRICTED   |                  P=0.363N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia Diffuse                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/47 (4%)                2/47 (4%)                1/46 (2%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.29                  2/46.38                  1/43.32                  0/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     4.3%                     2.3%                     0.0%            | 
|TERMINAL (d)       |                  1/40 (3%)                2/44 (5%)                1/40 (3%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  647                      727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.126N                 P=0.665N                 P=0.505N                 P=0.239N        | 
|POLY 3             |                  P=0.127N                 P=0.685N                 P=0.516N                 P=0.238N        | 
|POLY 1.5           |                  P=0.127N                 P=0.689N                 P=0.515N                 P=0.238N        | 
|POLY 6             |                  P=0.127N                 P=0.680N                 P=0.514N                 P=0.237N        | 
|LOGISTIC REGRESSION|                  P=0.119N                 P=0.646                  P=0.498N                 P=0.214N        | 
|COCH-ARM / FISHERS |                  P=0.121N                 P=0.692N                 P=0.508N                 P=0.242N        | 
|ORDER RESTRICTED   |                  P=0.156N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 24      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  11/47 (23%)              8/47 (17%)               4/46 (9%)                7/48 (15%)      | 
|POLY-3 RATE (b)    |                  11/45.00                 8/46.44                  4/43.32                  7/45.99         | 
|POLY-3 PERCENT (g) |                  24.5%                    17.2%                    9.2%                     15.2%           | 
|TERMINAL (d)       |                  11/40 (28%)              7/44 (16%)               4/40 (10%)               6/41 (15%)      | 
|FIRST INCIDENCE    |                  727 (T)                  711                      727 (T)                  318             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.163N                 P=0.228N                 P=0.044N*                P=0.200N        | 
|POLY 3             |                  P=0.155N                 P=0.278N                 P=0.051N                 P=0.200N        | 
|POLY 1.5           |                  P=0.156N                 P=0.290N                 P=0.051N                 P=0.206N        | 
|POLY 6             |                  P=0.152N                 P=0.260N                 P=0.048N*                P=0.191N        | 
|LOGISTIC REGRESSION|                  P=0.151N                 P=0.230N                 P=0.044N*                P=0.194N        | 
|COCH-ARM / FISHERS |                  P=0.148N                 P=0.304N                 P=0.049N*                P=0.202N        | 
|ORDER RESTRICTED   |                  P=0.090N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  4/43 (9%)                2/44 (5%)                3/43 (7%)                3/47 (6%)       | 
|POLY-3 RATE (b)    |                  4/41.73                  2/43.38                  3/40.21                  3/44.42         | 
|POLY-3 PERCENT (g) |                  9.6%                     4.6%                     7.5%                     6.8%            | 
|TERMINAL (d)       |                  3/37 (8%)                2/41 (5%)                2/37 (5%)                2/40 (5%)       | 
|FIRST INCIDENCE    |                  599                      727 (T)                  442                      633             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.496N                 P=0.298N                 P=0.509N                 P=0.470N        | 
|POLY 3             |                  P=0.484N                 P=0.319N                 P=0.520N                 P=0.466N        | 
|POLY 1.5           |                  P=0.482N                 P=0.323N                 P=0.518N                 P=0.466N        | 
|POLY 6             |                  P=0.483N                 P=0.315N                 P=0.517N                 P=0.462N        | 
|LOGISTIC REGRESSION|                  P=0.417N                 P=0.395N                 P=0.422N                 P=0.431N        | 
|COCH-ARM / FISHERS |                  P=0.465N                 P=0.327N                 P=0.500N                 P=0.450N        | 
|ORDER RESTRICTED   |                  P=0.432N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 25      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Ectopic Parathyroid Gland                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/43 (7%)                1/44 (2%)                2/43 (5%)                3/47 (6%)       | 
|POLY-3 RATE (b)    |                  3/41.29                  1/43.38                  2/39.44                  3/44.08         | 
|POLY-3 PERCENT (g) |                  7.3%                     2.3%                     5.1%                     6.8%            | 
|TERMINAL (d)       |                  3/37 (8%)                1/41 (2%)                2/37 (5%)                3/40 (8%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.483                  P=0.269N                 P=0.500N                 P=0.627N        | 
|POLY 3             |                  P=0.483                  P=0.288N                 P=0.521N                 P=0.632N        | 
|POLY 1.5           |                  P=0.486                  P=0.292N                 P=0.519N                 P=0.632N        | 
|POLY 6             |                  P=0.483                  P=0.282N                 P=0.518N                 P=0.628N        | 
|LOGISTIC REGRESSION|                  P=0.483                  P=0.269N                 P=0.500N                 P=0.627N        | 
|COCH-ARM / FISHERS |                  P=0.503                  P=0.299N                 P=0.500N                 P=0.618N        | 
|ORDER RESTRICTED   |                  P=0.475N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/43 (7%)                5/44 (11%)               6/43 (14%)               2/47 (4%)       | 
|POLY-3 RATE (b)    |                  3/41.29                  5/43.38                  6/39.44                  2/44.08         | 
|POLY-3 PERCENT (g) |                  7.3%                     11.5%                    15.2%                    4.5%            | 
|TERMINAL (d)       |                  3/37 (8%)                5/41 (12%)               6/37 (16%)               2/40 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.332N                 P=0.413                  P=0.240                  P=0.464N        | 
|POLY 3             |                  P=0.333N                 P=0.384                  P=0.218                  P=0.470N        | 
|POLY 1.5           |                  P=0.332N                 P=0.377                  P=0.221                  P=0.471N        | 
|POLY 6             |                  P=0.330N                 P=0.393                  P=0.221                  P=0.467N        | 
|LOGISTIC REGRESSION|                  P=0.332N                 P=0.413                  P=0.240                  P=0.464N        | 
|COCH-ARM / FISHERS |                  P=0.310N                 P=0.370                  P=0.242                  P=0.457N        | 
|ORDER RESTRICTED   |                  P=0.225N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 26      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Ultimobranchial Cyst                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/47 (0%)                0/46 (0%)                2/46 (4%)                2/48 (4%)       | 
|POLY-3 RATE (b)    |                  0/44.14                  0/45.38                  2/43.84                  2/45.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     0.0%                     4.6%                     4.4%            | 
|TERMINAL (d)       |                  0/39 (0%)                0/43 (0%)                1/40 (3%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  ---                      ---                      568                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.084                  (e)                      P=0.238                  P=0.249         | 
|POLY 3             |                  P=0.083                  (e)                      P=0.236                  P=0.242         | 
|POLY 1.5           |                  P=0.083                  (e)                      P=0.233                  P=0.240         | 
|POLY 6             |                  P=0.084                  (e)                      P=0.240                  P=0.245         | 
|LOGISTIC REGRESSION|                  P=0.094                  (e)                      P=0.251                  P=0.249         | 
|COCH-ARM / FISHERS |                  P=0.087                  (e)                      P=0.242                  P=0.253         | 
|ORDER RESTRICTED   |                  P=0.115                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/47 (4%)                2/46 (4%)                3/46 (7%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  2/44.14                  2/45.38                  3/43.52                  1/45.17         | 
|POLY-3 PERCENT (g) |                  4.5%                     4.4%                     6.9%                     2.2%            | 
|TERMINAL (d)       |                  2/39 (5%)                2/43 (5%)                2/40 (5%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  673                      704             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.399N                 P=0.659N                 P=0.507                  P=0.480N        | 
|POLY 3             |                  P=0.402N                 P=0.684N                 P=0.494                  P=0.492N        | 
|POLY 1.5           |                  P=0.403N                 P=0.690N                 P=0.490                  P=0.495N        | 
|POLY 6             |                  P=0.397N                 P=0.676N                 P=0.502                  P=0.486N        | 
|LOGISTIC REGRESSION|                  P=0.400N                 P=0.659N                 P=0.490                  P=0.492N        | 
|COCH-ARM / FISHERS |                  P=0.394N                 P=0.683                  P=0.490                  P=0.492N        | 
|ORDER RESTRICTED   |                  P=0.389N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 27      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tongue: Artery                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                0/48 (0%)                0/48 (0%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  0/46.93                  0/43.58                  0/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     0.0%                     0.0%                     0.0%            | 
|TERMINAL (d)       |                  2/40 (5%)                0/44 (0%)                0/40 (0%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  ---                      ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.123N                 P=0.218N                 P=0.238N                 P=0.233N        | 
|POLY 3             |                  P=0.126N                 P=0.229N                 P=0.245N                 P=0.237N        | 
|POLY 1.5           |                  P=0.125N                 P=0.232N                 P=0.244N                 P=0.239N        | 
|POLY 6             |                  P=0.128N                 P=0.225N                 P=0.243N                 P=0.234N        | 
|LOGISTIC REGRESSION|                  P=0.123N                 (e)                      (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.122N                 P=0.247N                 P=0.247N                 P=0.247N        | 
|ORDER RESTRICTED   |                  P=0.029N*                (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Inclusion Body Intracytoplasmic                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  7/47 (15%)               15/46 (33%)              34/45 (76%)              39/48 (81%)     | 
|POLY-3 RATE (b)    |                  7/45.00                  15/45.38                 34/43.09                 39/45.08        | 
|POLY-3 PERCENT (g) |                  15.6%                    33.1%                    78.9%                    86.5%           | 
|TERMINAL (d)       |                  7/40 (18%)               15/43 (35%)              33/39 (85%)              39/41 (95%)     | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  442                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P<0.001 **               P=0.062                  P<0.001 **               P<0.001 **      | 
|POLY 3             |                  P<0.001 **               P=0.043 *                P<0.001 **               P<0.001 **      | 
|POLY 1.5           |                  P<0.001 **               P=0.040 *                P<0.001 **               P<0.001 **      | 
|POLY 6             |                  P<0.001 **               P=0.048 *                P<0.001 **               P<0.001 **      | 
|LOGISTIC REGRESSION|                  P<0.001 **               P=0.062                  P<0.001 **               P<0.001 **      | 
|COCH-ARM / FISHERS |                  P<0.001 **               P=0.038 *                P<0.001 **               P<0.001 **      | 
|ORDER RESTRICTED   |                  P<0.001 **               (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 28      
Statistical Analysis of Non-neoplastic Lesions in       Mice(C57BL/6NXC3H/HEN MTN-NCTR)  -                      MALACHITE GREEN     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  36/47 (77%)              34/46 (74%)              33/45 (73%)              25/48 (52%)     | 
|POLY-3 RATE (b)    |                  36/45.94                 34/45.38                 33/43.04                 25/45.65        | 
|POLY-3 PERCENT (g) |                  78.4%                    74.9%                    76.7%                    54.8%           | 
|TERMINAL (d)       |                  33/40 (83%)              34/43 (79%)              31/39 (80%)              23/41 (56%)     | 
|FIRST INCIDENCE    |                  599                      727 (T)                  568                      626             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.007N**               P=0.194N                 P=0.397N                 P=0.012N*       | 
|POLY 3             |                  P=0.006N**               P=0.444N                 P=0.525N                 P=0.012N*       | 
|POLY 1.5           |                  P=0.006N**               P=0.457N                 P=0.520N                 P=0.013N*       | 
|POLY 6             |                  P=0.005N**               P=0.426N                 P=0.505N                 P=0.010N*       | 
|LOGISTIC REGRESSION|                  P=0.007N**               P=0.315N                 P=0.530N                 P=0.014N*       | 
|COCH-ARM / FISHERS |                  P=0.004N**               P=0.476N                 P=0.452N                 P=0.011N*       | 
|ORDER RESTRICTED   |                  P=0.006N**               (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  42/48 (88%)              46/48 (96%)              44/47 (94%)              42/48 (88%)     | 
|POLY-3 RATE (b)    |                  42/45.97                 46/47.94                 44/46.10                 42/45.38        | 
|POLY-3 PERCENT (g) |                  91.4%                    96.0%                    95.5%                    92.6%           | 
|TERMINAL (d)       |                  39/40 (98%)              43/44 (98%)              39/40 (98%)              40/41 (98%)     | 
|FIRST INCIDENCE    |                  599                      596                      226                      673             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.459N                 P=0.635N                 P=0.362                  P=0.498N        | 
|POLY 3             |                  P=0.584N                 P=0.298                  P=0.342                  P=0.576         | 
|POLY 1.5           |                  P=0.563N                 P=0.218                  P=0.296                  P=0.552         | 
|POLY 6             |                  P=0.579N                 P=0.422                  P=0.429                  P=0.634         | 
|LOGISTIC REGRESSION|                  P=0.567                  P=0.301                  P=0.152                  P=0.586N        | 
|COCH-ARM / FISHERS |                  P=0.398N                 P=0.134                  P=0.254                  P=0.621N        | 
|ORDER RESTRICTED   |                  P=0.382                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
                                                                                                                                   
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.