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TR 341 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  NITROFURANTOIN                                    DATE: 09/07/94       
EXPERIMENT: 05051 TEST: 01                                                                                     TIME: 07:13:27       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NOIES28024            ROUTE: DOSED FEED                                                                  NTP C#: C55196       
PATHOLOGIST: R. THOMPSON                                                                                       CAS: 67-20-9         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Southern Research Inst                                  NITROFURANTOIN                                    DATE: 09/07/94      
EXPERIMENT: 05051 TEST: 01                                                                                     TIME: 07:13:27      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NOIES28024            ROUTE: DOSED FEED                                                                  NTP C#: C55196      
PATHOLOGIST: R. THOMPSON                                                                                       CAS: 67-20-9        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  NITROFURANTOIN                                    DATE: 09/07/94       
EXPERIMENT: 05051 TEST: 01                                                                                     TIME: 07:13:27       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NOIES28024            ROUTE: DOSED FEED                                                                  NTP C#: C55196       
PATHOLOGIST: R. THOMPSON                                                                                       CAS: 67-20-9         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                         IN THE ANALYSIS OF THE STUDY OF NITROFURANTOIN
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Testes                        Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                             Mammary Gland                 Carcinoma
                                                           Carcinoma or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Carcinoma
                             Skin                          Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,
                                                            Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma
                             All Organs                    Malignant Tumors
 
              ====================================================================================================
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       2/49 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.3%          |      0.0%            7.3%            2.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       1/26 (4%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             632           |      ---             728             693           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.303           (e)           P=0.530        |     P=0.424         P=0.244         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.227           (e)           P=0.410        |     P=0.306         P=0.190         P=0.383        |
|LOGISTIC REGRESSION    |     P=0.285           (e)           P=0.500        |     P=0.385         P=0.227         P=0.497        |
|COCHRAN-ARMITAGE       |     P=0.283                                        |     P=0.392                                        |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.242         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     20/50 (40%)     23/50 (46%)     |     2/48 (4%)       1/48 (2%)       4/50 (8%)      |
|ADJUSTED (b)           |     71.1%           63.3%           64.5%          |      7.6%            4.0%           11.6%          |
|TERMINAL (d)           |    15/24 (63%)     16/27 (59%)     14/26 (54%)     |     1/25 (4%)       1/25 (4%)       3/31 (10%)     |
|FIRST INCIDENCE (DAYS) |      591             548             559           |      729             730 (T)         491           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.403N        P=0.177N        P=0.443N       |     P=0.297         P=0.504N        P=0.413        |
|INCIDENTAL TUMOR       |     P=0.485N        P=0.188N        P=0.536N       |     P=0.288         P=0.556N        P=0.412        |
|LOGISTIC REGRESSION    |     P=0.433N        P=0.163N        P=0.477N       |     P=0.236         P=0.520N        P=0.353        |
|COCHRAN-ARMITAGE       |     P=0.535N                                       |     P=0.244                                        |
|FISHER EXACT           |                     P=0.343N        P=0.579N       |                     P=0.500N        P=0.359        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       1/50 (2%)       2/50 (4%)      |     0/48 (0%)       0/48 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |     11.7%            3.1%            7.7%          |      0.0%            0.0%            2.2%          |
|TERMINAL (d)           |     2/24 (8%)       0/27 (0%)       2/26 (8%)      |     0/25 (0%)       0/25 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729             722             730 (T)       |      ---             ---             491           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.376N        P=0.276N        P=0.474N       |     P=0.270           (e)           P=0.492        |
|INCIDENTAL TUMOR       |     P=0.361N        P=0.244N        P=0.463N       |     P=0.350           (e)           P=0.638        |
|LOGISTIC REGRESSION    |     P=0.365N        P=0.247N        P=0.486N       |     P=0.346           (e)           P=0.670        |
|COCHRAN-ARMITAGE       |     P=0.395N                                       |     P=0.281                                        |
|FISHER EXACT           |                     P=0.309N        P=0.500N       |                       (e)           P=0.510        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    24/50 (48%)     21/50 (42%)     23/50 (46%)     |     2/48 (4%)       1/48 (2%)       4/50 (8%)      |
|ADJUSTED (b)           |     74.3%           64.5%           64.5%          |      7.6%            4.0%           11.6%          |
|TERMINAL (d)           |    16/24 (67%)     16/27 (59%)     14/26 (54%)     |     1/25 (4%)       1/25 (4%)       3/31 (10%)     |
|FIRST INCIDENCE (DAYS) |      591             548             559           |      729             730 (T)         491           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.330N        P=0.174N        P=0.368N       |     P=0.297         P=0.504N        P=0.413        |
|INCIDENTAL TUMOR       |     P=0.396N        P=0.178N        P=0.448N       |     P=0.288         P=0.556N        P=0.412        |
|LOGISTIC REGRESSION    |     P=0.345N        P=0.152N        P=0.386N       |     P=0.236         P=0.520N        P=0.353        |
|COCHRAN-ARMITAGE       |     P=0.456N                                       |     P=0.244                                        |
|FISHER EXACT           |                     P=0.344N        P=0.500N       |                     P=0.500N        P=0.359        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.7%            4.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         386           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.150         P=0.523         P=0.237        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.188         P=0.523         P=0.277        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.160         P=0.523         P=0.318        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.145                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/48 (13%)      5/50 (10%)      0/47 (0%)      |     1/44 (2%)       7/38 (18%)      4/42 (10%)     |
|ADJUSTED (b)           |     21.9%           15.2%            0.0%          |      2.4%           26.8%           13.3%          |
|TERMINAL (d)           |     4/22 (18%)      3/27 (11%)      0/26 (0%)      |     0/23 (0%)       5/22 (23%)      3/28 (11%)     |
|FIRST INCIDENCE (DAYS) |      533             630             ---           |      658             621             700           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.011N*       P=0.388N        P=0.013N*      |     P=0.270         P=0.027 *       P=0.212        |
|INCIDENTAL TUMOR       |     P=0.026N*       P=0.565N        P=0.021N*      |     P=0.206         P=0.023 *       P=0.139        |
|LOGISTIC REGRESSION    |     P=0.018N*       P=0.461N        P=0.018N*      |     P=0.189         P=0.018 *       P=0.163        |
|COCHRAN-ARMITAGE       |     P=0.019N*                                      |     P=0.191                                        |
|FISHER EXACT           |                     P=0.471N        P=0.014N*      |                     P=0.017 *       P=0.166        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/48 (13%)      6/50 (12%)      0/47 (0%)      |     4/44 (9%)       3/38 (8%)       0/42 (0%)      |
|ADJUSTED (b)           |     18.3%           17.3%            0.0%          |     14.1%           13.6%            0.0%          |
|TERMINAL (d)           |     2/22 (9%)       2/27 (7%)       0/26 (0%)      |     2/23 (9%)       3/22 (14%)      0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      455             320             ---           |      633             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.019N*       P=0.522N        P=0.015N*      |     P=0.036N*       P=0.532N        P=0.052N       |
|INCIDENTAL TUMOR       |     P=0.024N*       P=0.504N        P=0.031N*      |     P=0.039N*       P=0.498N        P=0.057N       |
|LOGISTIC REGRESSION    |     P=0.037N*       P=0.603         P=0.028N*      |     P=0.057N        P=0.607N        P=0.069N       |
|COCHRAN-ARMITAGE       |     P=0.024N*                                      |     P=0.055N                                       |
|FISHER EXACT           |                     P=0.591N        P=0.014N*      |                     P=0.583N        P=0.064N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/48 (25%)     11/50 (22%)      0/47 (0%)      |     5/44 (11%)     10/38 (26%)      4/42 (10%)     |
|ADJUSTED (b)           |     37.6%           30.6%            0.0%          |     16.1%           39.7%           13.3%          |
|TERMINAL (d)           |     6/22 (27%)      5/27 (19%)      0/26 (0%)      |     2/23 (9%)       8/22 (36%)      3/28 (11%)     |
|FIRST INCIDENCE (DAYS) |      455             320             ---           |      633             621             700           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001N**      P=0.352N        P<0.001N**     |     P=0.315N        P=0.107         P=0.436N       |
|INCIDENTAL TUMOR       |     P=0.001N**      P=0.455N        P<0.001N**     |     P=0.387N        P=0.106         P=0.533N       |
|LOGISTIC REGRESSION    |     P=0.001N**      P=0.494N        P<0.001N**     |     P=0.449N        P=0.063         P=0.533N       |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |     P=0.443N                                       |
|FISHER EXACT           |                     P=0.455N        P<0.001N**     |                     P=0.072         P=0.530N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       1/49 (2%)      |     0/50 (0%)       0/48 (0%)       0/49 (0%)      |
|ADJUSTED (b)           |      8.3%            6.5%            3.4%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         712             719           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.372N        P=0.648N        P=0.477N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.377N        P=0.640N        P=0.481N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.369N        P=0.636N        P=0.475N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.404N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.691N        P=0.508N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/49 (4%)      |     1/50 (2%)       0/48 (0%)       0/49 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            7.7%          |      4.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       2/26 (8%)      |     1/25 (4%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             730 (T)       |      730 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.108           (e)           P=0.255        |     P=0.268N        P=0.492N        P=0.457N       |
|INCIDENTAL TUMOR       |     P=0.108           (e)           P=0.255        |     P=0.268N        P=0.492N        P=0.457N       |
|LOGISTIC REGRESSION    |     P=0.108           (e)           P=0.255        |     P=0.268N        P=0.492N        P=0.457N       |
|COCHRAN-ARMITAGE       |     P=0.100                                        |     P=0.300N                                       |
|FISHER EXACT           |                       (e)           P=0.242        |                     P=0.510N        P=0.505N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       3/49 (6%)      |     1/50 (2%)       0/48 (0%)       0/49 (0%)      |
|ADJUSTED (b)           |      8.3%            6.5%           10.9%          |      4.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/27 (4%)       2/26 (8%)      |     1/25 (4%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         712             719           |      730 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.443         P=0.648N        P=0.532        |     P=0.268N        P=0.492N        P=0.457N       |
|INCIDENTAL TUMOR       |     P=0.437         P=0.640N        P=0.529        |     P=0.268N        P=0.492N        P=0.457N       |
|LOGISTIC REGRESSION    |     P=0.441         P=0.636N        P=0.530        |     P=0.268N        P=0.492N        P=0.457N       |
|COCHRAN-ARMITAGE       |     P=0.404                                        |     P=0.300N                                       |
|FISHER EXACT           |                     P=0.691N        P=0.490        |                     P=0.510N        P=0.505N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            3.7%            7.7%          |      0.0%            0.0%            3.2%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       2/26 (8%)      |     0/25 (0%)       0/26 (0%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         730 (T)       |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.154         P=0.523         P=0.255        |     P=0.309           (e)           P=0.543        |
|INCIDENTAL TUMOR       |     P=0.154         P=0.523         P=0.255        |     P=0.309           (e)           P=0.543        |
|LOGISTIC REGRESSION    |     P=0.154         P=0.523         P=0.255        |     P=0.309           (e)           P=0.543        |
|COCHRAN-ARMITAGE       |     P=0.145                                        |     P=0.275                                        |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            3.7%           10.9%          |      0.0%            0.0%            3.2%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       2/26 (8%)      |     0/25 (0%)       0/26 (0%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         719           |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.068         P=0.523         P=0.134        |     P=0.309           (e)           P=0.543        |
|INCIDENTAL TUMOR       |     P=0.069         P=0.523         P=0.137        |     P=0.309           (e)           P=0.543        |
|LOGISTIC REGRESSION    |     P=0.066         P=0.523         P=0.134        |     P=0.309           (e)           P=0.543        |
|COCHRAN-ARMITAGE       |     P=0.063                                        |     P=0.275                                        |
|FISHER EXACT           |                     P=0.500         P=0.121        |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       3/50 (6%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            9.9%            0.0%          |      0.0%            3.6%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       2/27 (7%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         699             ---           |      ---             728             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.366N        P=0.360         P=0.484N       |     P=0.708N        P=0.500           (e)          |
|INCIDENTAL TUMOR       |     P=0.371N        P=0.360         P=0.484N       |     P=0.686         P=0.419           (e)          |
|LOGISTIC REGRESSION    |     P=0.369N        P=0.360         P=0.484N       |     P=0.723N        P=0.494           (e)          |
|COCHRAN-ARMITAGE       |     P=0.399N                                       |     P=0.725N                                       |
|FISHER EXACT           |                     P=0.309         P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       4/50 (8%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%           13.5%            0.0%          |      0.0%            3.6%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       3/27 (11%)      0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         699             ---           |      ---             728             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.379N        P=0.225         P=0.484N       |     P=0.708N        P=0.500           (e)          |
|INCIDENTAL TUMOR       |     P=0.384N        P=0.225         P=0.484N       |     P=0.686         P=0.419           (e)          |
|LOGISTIC REGRESSION    |     P=0.380N        P=0.228         P=0.484N       |     P=0.723N        P=0.494           (e)          |
|COCHRAN-ARMITAGE       |     P=0.415N                                       |     P=0.725N                                       |
|FISHER EXACT           |                     P=0.181         P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       4/50 (8%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%           13.5%            0.0%          |      0.0%            3.6%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       3/27 (11%)      0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         699             ---           |      ---             728             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.379N        P=0.225         P=0.484N       |     P=0.708N        P=0.500           (e)          |
|INCIDENTAL TUMOR       |     P=0.384N        P=0.225         P=0.484N       |     P=0.686         P=0.419           (e)          |
|LOGISTIC REGRESSION    |     P=0.380N        P=0.228         P=0.484N       |     P=0.723N        P=0.494           (e)          |
|COCHRAN-ARMITAGE       |     P=0.415N                                       |     P=0.725N                                       |
|FISHER EXACT           |                     P=0.181         P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     2/50 (4%)       2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      7.2%            6.4%            5.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     1/25 (4%)       1/26 (4%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      727             665             686           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.559N        P=0.689         P=0.651N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.534         P=0.628         P=0.631        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.595         P=0.670         P=0.685        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.608                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.691N        P=0.691N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |     11.1%            6.4%            5.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     2/25 (8%)       1/26 (4%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      727             665             686           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.365N        P=0.499N        P=0.439N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.473N        P=0.562N        P=0.546N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.432N        P=0.534N        P=0.512N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.418N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     6/50 (12%)      5/50 (10%)      0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |     19.4%           17.2%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     3/25 (12%)      3/26 (12%)      0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      661             687             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.013N*       P=0.497N        P=0.015N*      |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.027N*       P=0.612N        P=0.027N*      |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.018N*       P=0.553N        P=0.019N*      |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.016N*                                      |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500N        P=0.013N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     6/50 (12%)      5/50 (10%)      0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            0.0%            0.0%          |     19.4%           17.2%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       0/27 (0%)       0/26 (0%)      |     3/25 (12%)      3/26 (12%)      0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      661             687             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.259N        P=0.477N        P=0.484N       |     P=0.013N*       P=0.497N        P=0.015N*      |
|INCIDENTAL TUMOR       |     P=0.259N        P=0.477N        P=0.484N       |     P=0.027N*       P=0.612N        P=0.027N*      |
|LOGISTIC REGRESSION    |     P=0.259N        P=0.477N        P=0.484N       |     P=0.018N*       P=0.553N        P=0.019N*      |
|COCHRAN-ARMITAGE       |     P=0.272N                                       |     P=0.016N*                                      |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500N        P=0.013N*      |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       4/50 (8%)       2/50 (4%)      |    28/50 (56%)     26/50 (52%)     31/50 (62%)     |
|ADJUSTED (b)           |      8.3%           12.4%            5.8%          |     70.4%           69.0%           79.2%          |
|TERMINAL (d)           |     2/24 (8%)       2/27 (7%)       0/26 (0%)      |    14/25 (56%)     15/26 (58%)     23/31 (74%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         644             635           |      428             456             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.568N        P=0.402         P=0.663N       |     P=0.503N        P=0.449N        P=0.517N       |
|INCIDENTAL TUMOR       |     P=0.551         P=0.346         P=0.676        |     P=0.246         P=0.551N        P=0.309        |
|LOGISTIC REGRESSION    |     P=0.584N        P=0.390         P=0.681N       |     P=0.230         P=0.507N        P=0.262        |
|COCHRAN-ARMITAGE       |     P=0.582                                        |     P=0.297                                        |
|FISHER EXACT           |                     P=0.339         P=0.691N       |                     P=0.421N        P=0.342        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)       2/50 (4%)      |    28/50 (56%)     26/50 (52%)     31/50 (62%)     |
|ADJUSTED (b)           |     12.5%           12.4%            5.8%          |     70.4%           69.0%           79.2%          |
|TERMINAL (d)           |     3/24 (13%)      2/27 (7%)       0/26 (0%)      |    14/25 (56%)     15/26 (58%)     23/31 (74%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         644             635           |      428             456             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.391N        P=0.572         P=0.463N       |     P=0.503N        P=0.449N        P=0.517N       |
|INCIDENTAL TUMOR       |     P=0.451N        P=0.519         P=0.511N       |     P=0.246         P=0.551N        P=0.309        |
|LOGISTIC REGRESSION    |     P=0.403N        P=0.569         P=0.476N       |     P=0.230         P=0.507N        P=0.262        |
|COCHRAN-ARMITAGE       |     P=0.427N                                       |     P=0.297                                        |
|FISHER EXACT           |                     P=0.500         P=0.500N       |                     P=0.421N        P=0.342        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)       2/50 (4%)      |    30/50 (60%)     29/50 (58%)     31/50 (62%)     |
|ADJUSTED (b)           |     12.5%           12.4%            5.8%          |     74.0%           75.5%           79.2%          |
|TERMINAL (d)           |     3/24 (13%)      2/27 (7%)       0/26 (0%)      |    15/25 (60%)     17/26 (65%)     23/31 (74%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         644             635           |      428             456             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.391N        P=0.572         P=0.463N       |     P=0.350N        P=0.510N        P=0.377N       |
|INCIDENTAL TUMOR       |     P=0.451N        P=0.519         P=0.511N       |     P=0.387         P=0.502         P=0.457        |
|LOGISTIC REGRESSION    |     P=0.403N        P=0.569         P=0.476N       |     P=0.369         P=0.548         P=0.407        |
|COCHRAN-ARMITAGE       |     P=0.427N                                       |     P=0.456                                        |
|FISHER EXACT           |                     P=0.500         P=0.500N       |                     P=0.500N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/49 (0%)      |     0/50 (0%)       1/48 (2%)       0/49 (0%)      |
|ADJUSTED (b)           |      7.2%            0.0%            0.0%          |      0.0%            3.8%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       1/26 (4%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      677             ---             ---           |      ---             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.083N        P=0.206N        P=0.221N       |     P=0.691N        P=0.508           (e)          |
|INCIDENTAL TUMOR       |     P=0.086N        P=0.201N        P=0.231N       |     P=0.691N        P=0.508           (e)          |
|LOGISTIC REGRESSION    |     P=0.091N        P=0.221N        P=0.233N       |     P=0.691N        P=0.508           (e)          |
|COCHRAN-ARMITAGE       |     P=0.096N                                       |     P=0.727N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.253N       |                     P=0.490           (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/50 (20%)     12/50 (24%)     13/50 (26%)     |    23/50 (46%)     16/48 (33%)     21/48 (44%)     |
|ADJUSTED (b)           |     27.8%           32.1%           42.3%          |     59.1%           50.4%           51.7%          |
|TERMINAL (d)           |     3/24 (13%)      5/27 (19%)      9/26 (35%)     |    11/25 (44%)     11/26 (42%)     12/31 (39%)     |
|FIRST INCIDENCE (DAYS) |      506             489             646           |      568             567             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.355         P=0.520         P=0.401        |     P=0.264N        P=0.148N        P=0.293N       |
|INCIDENTAL TUMOR       |     P=0.286         P=0.328         P=0.338        |     P=0.517         P=0.145N        P=0.500        |
|LOGISTIC REGRESSION    |     P=0.282         P=0.371         P=0.333        |     P=0.523         P=0.163N        P=0.551        |
|COCHRAN-ARMITAGE       |     P=0.278                                        |     P=0.471N                                       |
|FISHER EXACT           |                     P=0.405         P=0.318        |                     P=0.141N        P=0.492N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       3/50 (6%)      |     3/50 (6%)       9/48 (19%)      2/48 (4%)      |
|ADJUSTED (b)           |      4.2%            6.0%            8.4%          |      9.7%           26.9%            5.6%          |
|TERMINAL (d)           |     1/24 (4%)       1/27 (4%)       1/26 (4%)      |     1/25 (4%)       4/26 (15%)      1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         644             387           |      700             564             675           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.248         P=0.548         P=0.333        |     P=0.342N        P=0.069         P=0.462N       |
|INCIDENTAL TUMOR       |     P=0.235         P=0.458         P=0.350        |     P=0.562N        P=0.033 *       P=0.646N       |
|LOGISTIC REGRESSION    |     P=0.223         P=0.522         P=0.303        |     P=0.426N        P=0.048 *       P=0.527N       |
|COCHRAN-ARMITAGE       |     P=0.225                                        |     P=0.417N                                       |
|FISHER EXACT           |                     P=0.500         P=0.309        |                     P=0.052         P=0.520N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/50 (22%)     14/50 (28%)     16/50 (32%)     |    26/50 (52%)     25/48 (52%)     23/48 (48%)     |
|ADJUSTED (b)           |     31.2%           36.7%           48.3%          |     64.3%           68.6%           55.4%          |
|TERMINAL (d)           |     4/24 (17%)      6/27 (22%)     10/26 (38%)     |    12/25 (48%)     15/26 (58%)     13/31 (42%)     |
|FIRST INCIDENCE (DAYS) |      506             489             387           |      568             564             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.232         P=0.453         P=0.268        |     P=0.192N        P=0.524N        P=0.236N       |
|INCIDENTAL TUMOR       |     P=0.165         P=0.243         P=0.214        |     P=0.525         P=0.511         P=0.518        |
|LOGISTIC REGRESSION    |     P=0.157         P=0.297         P=0.188        |     P=0.501N        P=0.448         P=0.558N       |
|COCHRAN-ARMITAGE       |     P=0.157                                        |     P=0.381N                                       |
|FISHER EXACT           |                     P=0.322         P=0.184        |                     P=0.577         P=0.420N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |     10.6%            0.0%            9.7%          |      0.0%            0.0%            2.9%          |
|TERMINAL (d)           |     2/24 (8%)       0/27 (0%)       2/26 (8%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      621             ---             559           |      ---             ---             699           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.563N        P=0.105N        P=0.631N       |     P=0.274           (e)           P=0.494        |
|INCIDENTAL TUMOR       |     P=0.574         P=0.141N        P=0.619        |     P=0.198           (e)           P=0.383        |
|LOGISTIC REGRESSION    |     P=0.588N        P=0.113N        P=0.660N       |     P=0.272           (e)           P=0.495        |
|COCHRAN-ARMITAGE       |     P=0.589N                                       |     P=0.275                                        |
|FISHER EXACT           |                     P=0.121N        P=0.661N       |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       6/50 (12%)      4/50 (8%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |     11.9%           19.1%           14.5%          |      0.0%            0.0%            2.5%          |
|TERMINAL (d)           |     1/24 (4%)       4/27 (15%)      3/26 (12%)     |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      455             644             716           |      ---             ---             675           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.535N        P=0.441         P=0.614N       |     P=0.291           (e)           P=0.516        |
|INCIDENTAL TUMOR       |     P=0.569         P=0.323         P=0.623N       |     P=0.198           (e)           P=0.383        |
|LOGISTIC REGRESSION    |     P=0.569N        P=0.367         P=0.642N       |     P=0.276           (e)           P=0.505        |
|COCHRAN-ARMITAGE       |     P=0.564                                        |     P=0.275                                        |
|FISHER EXACT           |                     P=0.370         P=0.643N       |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      3.2%            3.7%            7.3%          |      0.0%            3.8%            3.2%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       1/26 (4%)      |     0/25 (0%)       1/26 (4%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      678             730 (T)         728           |      ---             730 (T)         730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.411         P=0.721N        P=0.527        |     P=0.402         P=0.508         P=0.543        |
|INCIDENTAL TUMOR       |     P=0.411         P=0.720N        P=0.530        |     P=0.402         P=0.508         P=0.543        |
|LOGISTIC REGRESSION    |     P=0.407         P=0.748N        P=0.522        |     P=0.402         P=0.508         P=0.543        |
|COCHRAN-ARMITAGE       |     P=0.386                                        |     P=0.352                                        |
|FISHER EXACT           |                     P=0.753N        P=0.500        |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     8/50 (16%)      7/50 (14%)      9/50 (18%)     |     0/50 (0%)       1/50 (2%)       3/50 (6%)      |
|ADJUSTED (b)           |     24.1%           22.6%           29.9%          |      0.0%            3.8%            8.3%          |
|TERMINAL (d)           |     3/24 (13%)      5/27 (19%)      6/26 (23%)     |     0/25 (0%)       1/26 (4%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      455             644             559           |      ---             730 (T)         675           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.512         P=0.407N        P=0.551        |     P=0.080         P=0.508         P=0.140        |
|INCIDENTAL TUMOR       |     P=0.444         P=0.543N        P=0.498        |     P=0.046 *       P=0.508         P=0.069        |
|LOGISTIC REGRESSION    |     P=0.467         P=0.490N        P=0.510        |     P=0.060         P=0.508         P=0.116        |
|COCHRAN-ARMITAGE       |     P=0.452                                        |     P=0.062                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500        |                     P=0.500         P=0.121        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       5/50 (10%)      4/50 (8%)      |     1/50 (2%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%           16.2%           15.4%          |      4.0%            6.4%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       3/27 (11%)      4/26 (15%)     |     1/25 (4%)       1/26 (4%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             644             730 (T)       |      730 (T)         653             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.077         P=0.047 *       P=0.071        |     P=0.319N        P=0.497         P=0.457N       |
|INCIDENTAL TUMOR       |     P=0.067         P=0.034 *       P=0.071        |     P=0.365N        P=0.463         P=0.457N       |
|LOGISTIC REGRESSION    |     P=0.076         P=0.042 *       P=0.071        |     P=0.359N        P=0.480         P=0.457N       |
|COCHRAN-ARMITAGE       |     P=0.067                                        |     P=0.350N                                       |
|FISHER EXACT           |                     P=0.028 *       P=0.059        |                     P=0.500         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.7%            6.4%            2.5%          |      0.0%            3.8%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       1/26 (4%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      633             700             636           |      ---             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.599N        P=0.553         P=0.734N       |     P=0.691N        P=0.508           (e)          |
|INCIDENTAL TUMOR       |     P=0.551         P=0.473         P=0.661        |     P=0.691N        P=0.508           (e)          |
|LOGISTIC REGRESSION    |     P=0.619         P=0.506         P=0.762        |     P=0.691N        P=0.508           (e)          |
|COCHRAN-ARMITAGE       |     P=0.620                                        |     P=0.725N                                       |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            0.0%            0.0%          |      3.3%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      621             ---             ---           |      727             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.085N        P=0.212N        P=0.223N       |     P=0.293N        P=0.507N        P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.120N        P=0.274N        P=0.278N       |     P=0.384N        P=0.581N        P=0.617N       |
|LOGISTIC REGRESSION    |     P=0.096N        P=0.250N        P=0.238N       |     P=0.297N        P=0.508N        P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.095N                                       |     P=0.296N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.247N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       7/50 (14%)      5/50 (10%)     |     2/50 (4%)       3/50 (6%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.7%           21.9%           17.5%          |      6.9%           10.1%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       4/27 (15%)      4/26 (15%)     |     1/25 (4%)       2/26 (8%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      633             644             636           |      709             653             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127         P=0.054         P=0.128        |     P=0.169N        P=0.502         P=0.223N       |
|INCIDENTAL TUMOR       |     P=0.087         P=0.030 *       P=0.081        |     P=0.221N        P=0.438         P=0.276N       |
|LOGISTIC REGRESSION    |     P=0.109         P=0.039 *       P=0.109        |     P=0.202N        P=0.469         P=0.243N       |
|COCHRAN-ARMITAGE       |     P=0.101                                        |     P=0.192N                                       |
|FISHER EXACT           |                     P=0.030 *       P=0.102        |                     P=0.500         P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.7%            6.4%            2.5%          |      3.0%            3.8%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       1/26 (4%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      633             700             636           |      709             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.599N        P=0.553         P=0.734N       |     P=0.320N        P=0.756N        P=0.512N       |
|INCIDENTAL TUMOR       |     P=0.551         P=0.473         P=0.661        |     P=0.376N        P=0.721         P=0.617N       |
|LOGISTIC REGRESSION    |     P=0.619         P=0.506         P=0.762        |     P=0.342N        P=0.747         P=0.507N       |
|COCHRAN-ARMITAGE       |     P=0.620                                        |     P=0.336N                                       |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  19
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    47/50 (94%)     45/50 (90%)     21/50 (42%)     |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%           61.8%          |                                                    |
|TERMINAL (d)           |    24/24 (100%)    27/27 (100%)    14/26 (54%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      455             548             559           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001N**      P=0.162N        P<0.001N**     |                                                    |
|INCIDENTAL TUMOR       |     P<0.001N**      P=0.277N        P<0.001N**     |                                                    |
|LOGISTIC REGRESSION    |     P<0.001N**      P=0.221N        P<0.001N**     |                                                    |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |                                                    |
|FISHER EXACT           |                     P=0.357N        P<0.001N**     |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       7/50 (14%)      6/50 (12%)     |     3/50 (6%)       3/50 (6%)       4/50 (8%)      |
|ADJUSTED (b)           |     12.5%           22.6%           20.1%          |     11.4%           10.2%           12.9%          |
|TERMINAL (d)           |     3/24 (13%)      5/27 (19%)      4/26 (15%)     |     2/25 (8%)       0/26 (0%)       4/31 (13%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         561             639           |      729             726             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.241         P=0.207         P=0.285        |     P=0.514         P=0.656N        P=0.611        |
|INCIDENTAL TUMOR       |     P=0.205         P=0.180         P=0.252        |     P=0.370         P=0.541         P=0.557        |
|LOGISTIC REGRESSION    |     P=0.227         P=0.200         P=0.278        |     P=0.434         P=0.656         P=0.547        |
|COCHRAN-ARMITAGE       |     P=0.205                                        |     P=0.423                                        |
|FISHER EXACT           |                     P=0.159         P=0.243        |                     P=0.661N        P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  20
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       1/50 (2%)      |     4/50 (8%)       2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            8.4%            3.8%          |     13.8%            7.7%            6.5%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       1/26 (4%)      |     3/25 (12%)      2/26 (8%)       2/31 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             656             730 (T)       |      481             730 (T)         730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.394         P=0.159         P=0.516        |     P=0.199N        P=0.326N        P=0.262N       |
|INCIDENTAL TUMOR       |     P=0.391         P=0.158         P=0.516        |     P=0.171N        P=0.271N        P=0.212N       |
|LOGISTIC REGRESSION    |     P=0.373         P=0.121         P=0.516        |     P=0.276N        P=0.344N        P=0.339N       |
|COCHRAN-ARMITAGE       |     P=0.367                                        |     P=0.265N                                       |
|FISHER EXACT           |                     P=0.121         P=0.500        |                     P=0.339N        P=0.339N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       9/50 (18%)      7/50 (14%)     |     7/50 (14%)      5/50 (10%)      6/50 (12%)     |
|ADJUSTED (b)           |     12.5%           26.4%           23.7%          |     24.5%           17.1%           19.4%          |
|TERMINAL (d)           |     3/24 (13%)      5/27 (19%)      5/26 (19%)     |     5/25 (20%)      2/26 (8%)       6/31 (19%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         561             639           |      481             726             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.176         P=0.100         P=0.193        |     P=0.329N        P=0.372N        P=0.356N       |
|INCIDENTAL TUMOR       |     P=0.145         P=0.084         P=0.168        |     P=0.408N        P=0.418N        P=0.354N       |
|LOGISTIC REGRESSION    |     P=0.155         P=0.076         P=0.189        |     P=0.476N        P=0.425N        P=0.527N       |
|COCHRAN-ARMITAGE       |     P=0.140                                        |     P=0.453N                                       |
|FISHER EXACT           |                     P=0.061         P=0.159        |                     P=0.380N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  21
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            7.4%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       2/27 (7%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.677         P=0.264           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.677         P=0.264           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.677         P=0.264           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.658                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.247           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            9.7%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       2/27 (7%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             656             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.644N        P=0.150           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.646N        P=0.152           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.636         P=0.133           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.623                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.121           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  22
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |                                                    |      0.0%            0.0%            6.5%          |
|TERMINAL (d)           |                                                    |     0/25 (0%)       0/26 (0%)       2/31 (6%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.120           (e)           P=0.286        |
|INCIDENTAL TUMOR       |                                                    |     P=0.120           (e)           P=0.286        |
|LOGISTIC REGRESSION    |                                                    |     P=0.120           (e)           P=0.286        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.094                                        |
|FISHER EXACT           |                                                    |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     16/50 (32%)     10/50 (20%)     |
|ADJUSTED (b)           |                                                    |     32.8%           47.2%           30.2%          |
|TERMINAL (d)           |                                                    |     6/25 (24%)      9/26 (35%)      8/31 (26%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      633             601             700           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.377N        P=0.142         P=0.456N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.531         P=0.094         P=0.593        |
|LOGISTIC REGRESSION    |                                                    |     P=0.543         P=0.081         P=0.574        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.522N                                       |
|FISHER EXACT           |                                                    |                     P=0.127         P=0.598N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  23
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |                                                    |      6.1%            2.0%            2.8%          |
|TERMINAL (d)           |                                                    |     1/25 (4%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      620             423             693           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.386N        P=0.511N        P=0.483N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.394N        P=0.372N        P=0.575N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.342N        P=0.381N        P=0.496N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.393N                                       |
|FISHER EXACT           |                                                    |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    11/50 (22%)     17/50 (34%)     11/50 (22%)     |
|ADJUSTED (b)           |                                                    |     34.3%           48.3%           32.1%          |
|TERMINAL (d)           |                                                    |     6/25 (24%)      9/26 (35%)      8/31 (26%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      620             423             693           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.385N        P=0.149         P=0.462N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.521         P=0.124         P=0.549        |
|LOGISTIC REGRESSION    |                                                    |     P=0.539         P=0.101         P=0.560        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.521N                                       |
|FISHER EXACT           |                                                    |                     P=0.133         P=0.595N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  24
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.1%            0.0%            2.2%          |      2.7%            2.5%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      554             ---             532           |      691             621             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.349N        P=0.219N        P=0.492N       |     P=0.346N        P=0.737         P=0.505N       |
|INCIDENTAL TUMOR       |     P=0.376N        P=0.274N        P=0.516N       |     P=0.426N        P=0.765         P=0.617N       |
|LOGISTIC REGRESSION    |     P=0.342N        P=0.250N        P=0.484N       |     P=0.323N        P=0.747N        P=0.502N       |
|COCHRAN-ARMITAGE       |     P=0.355N                                       |     P=0.336N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            2.0%            0.0%          |      3.3%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      621             483             ---           |      727             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.137N        P=0.468N        P=0.223N       |     P=0.293N        P=0.507N        P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.166N        P=0.619N        P=0.278N       |     P=0.384N        P=0.581N        P=0.617N       |
|LOGISTIC REGRESSION    |     P=0.138N        P=0.525N        P=0.238N       |     P=0.297N        P=0.508N        P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.145N                                       |     P=0.296N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  25
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            2.0%            2.6%          |      3.3%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      621             483             646           |      727             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.360N        P=0.468N        P=0.469N       |     P=0.293N        P=0.507N        P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.389N        P=0.619N        P=0.532N       |     P=0.384N        P=0.581N        P=0.617N       |
|LOGISTIC REGRESSION    |     P=0.373N        P=0.525N        P=0.502N       |     P=0.297N        P=0.508N        P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.380N                                       |     P=0.296N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     14/50 (28%)     15/50 (30%)     |    13/50 (26%)     13/50 (26%)      9/50 (18%)     |
|ADJUSTED (b)           |     57.0%           39.2%           38.1%          |     32.6%           33.7%           21.9%          |
|TERMINAL (d)           |     8/24 (33%)      7/27 (26%)      4/26 (15%)     |     2/25 (8%)       5/26 (19%)      2/31 (6%)      |
|FIRST INCIDENCE (DAYS) |      554             561             413           |      481             390             513           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.053N        P=0.037N*       P=0.076N       |     P=0.201N        P=0.545         P=0.243N       |
|INCIDENTAL TUMOR       |     P=0.069N        P=0.046N*       P=0.090N       |     P=0.307N        P=0.538N        P=0.454N       |
|LOGISTIC REGRESSION    |     P=0.086N        P=0.070N        P=0.122N       |     P=0.204N        P=0.447N        P=0.304N       |
|COCHRAN-ARMITAGE       |     P=0.055N                                       |     P=0.200N                                       |
|FISHER EXACT           |                     P=0.048N*       P=0.074N       |                     P=0.590N        P=0.235N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  26
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       6/50 (12%)      3/50 (6%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      9.3%           17.2%            8.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       2/27 (7%)       1/26 (4%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      506             630             635           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.538N        P=0.320         P=0.622N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.534         P=0.245         P=0.629        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.564         P=0.242         P=0.659        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.564                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.243         P=0.661N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.7%            4.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         386           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.150         P=0.523         P=0.237        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.188         P=0.523         P=0.277        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.160         P=0.523         P=0.318        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.145                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  27
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.7%            4.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/26 (0%)      |     0/25 (0%)       0/26 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         386           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.150         P=0.523         P=0.237        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.188         P=0.523         P=0.277        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.160         P=0.523         P=0.318        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.145                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     47/50 (94%)     40/50 (80%)     |    43/50 (86%)     41/50 (82%)     42/50 (84%)     |
|ADJUSTED (b)           |    100.0%          100.0%           95.1%          |     91.4%           93.2%           93.3%          |
|TERMINAL (d)           |    24/24 (100%)    27/27 (100%)    24/26 (92%)     |    21/25 (84%)     23/26 (88%)     28/31 (90%)     |
|FIRST INCIDENCE (DAYS) |      455             489             559           |      428             456             448           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.032N*       P=0.165N        P=0.043N*      |     P=0.199N        P=0.471N        P=0.221N       |
|INCIDENTAL TUMOR       |     P<0.001N**      P=0.362N        P=0.003N**     |     P=0.418         P=0.580         P=0.536        |
|LOGISTIC REGRESSION    |     P<0.001N**      P=0.224N        P=0.002N**     |     P=0.504         P=0.618         P=0.595        |
|COCHRAN-ARMITAGE       |     P=0.002N**                                     |     P=0.458N                                       |
|FISHER EXACT           |                     P=0.309N        P=0.004N**     |                     P=0.393N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  28
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.13%           0.25%         |      UNTREATD        0.06%           0.13%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    37/50 (74%)     31/50 (62%)     30/50 (60%)     |    31/50 (62%)     28/50 (56%)     18/50 (36%)     |
|ADJUSTED (b)           |     78.2%           68.2%           66.4%          |     69.5%           64.6%           40.8%          |
|TERMINAL (d)           |    14/24 (58%)     13/27 (48%)     12/26 (46%)     |    12/25 (48%)     12/26 (46%)      6/31 (19%)     |
|FIRST INCIDENCE (DAYS) |      455             320             386           |      481             390             412           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.111N        P=0.115N        P=0.131N       |     P=0.015N*       P=0.421N        P=0.019N*      |
|INCIDENTAL TUMOR       |     P=0.100N        P=0.162N        P=0.116N       |     P=0.016N*       P=0.348N        P=0.028N*      |
|LOGISTIC REGRESSION    |     P=0.101N        P=0.184N        P=0.153N       |     P=0.006N**      P=0.278N        P=0.012N*      |
|COCHRAN-ARMITAGE       |     P=0.085N                                       |     P=0.006N**                                     |
|FISHER EXACT           |                     P=0.142N        P=0.101N       |                     P=0.342N        P=0.008N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     50/50 (100%)    48/50 (96%)     |    49/50 (98%)     48/50 (96%)     46/50 (92%)     |
|ADJUSTED (b)           |    100.0%          100.0%           97.9%          |     98.0%           98.0%           95.8%          |
|TERMINAL (d)           |    24/24 (100%)    27/27 (100%)    25/26 (96%)     |    24/25 (96%)     25/26 (96%)     29/31 (94%)     |
|FIRST INCIDENCE (DAYS) |      455             320             386           |      428             390             412           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.285N        P=0.302N        P=0.315N       |     P=0.123N        P=0.533N        P=0.138N       |
|INCIDENTAL TUMOR       |     P=0.418N        P=0.638         P=0.545N       |     P=0.214N        P=0.587N        P=0.315N       |
|LOGISTIC REGRESSION    |     P=0.380N        P=0.364         P=0.503N       |     P=0.149N        P=0.535N        P=0.243N       |
|COCHRAN-ARMITAGE       |     P=0.377N                                       |     P=0.119N                                       |
|FISHER EXACT           |                     P=0.500         P=0.500N       |                     P=0.500N        P=0.181N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05051 TEST: 01                                                 PAGE  29
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NITROFURANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (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.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's 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. 
 (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).

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