National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/6873

TDMS Study 99033-01 Pathology Tables

                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/25/03       
EXPERIMENT: 99033 TEST: 01                                                                                     TIME: 09:00:46       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99033       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
Mice(TG.AC HETEROZYGOUS TRANSGENIC)                                                                                                 
-----------------------------                                                                                                       
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 THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Lung                                                                               
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/25/03       
EXPERIMENT: 99033 TEST: 01                                                                                     TIME: 09:00:46       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99033       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF       TRANSGENIC MODEL EVALUATION II (ASPA                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Stomach, Forestomach                   Squamous Cell Papilloma                                                                      
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
                                       Squamous Cell Papilloma                                                                      
All Organs                             Benign Tumors                                                                                
===============================================================                                                                     
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 1       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)        -        TRANSGENIC MODEL EVALUATION II (ASPA  
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        2/14 (14%)       1/15 (7%)        2/14 (14%)       2/14 (14%)      | 
|POLY-3 RATE (b)    |        0/12.30          0/14.31          2/10.17          1/13.78          2/12.66          2/11.92         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             19.7%            7.3%             15.8%            16.8%           | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        2/8 (25%)        1/12 (8%)        2/11 (18%)       2/10 (20%)      | 
|FIRST INCIDENCE    |        ---              ---              274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.128          (e)              P=0.207          P=0.557          P=0.280          P=0.257         | 
|POLY 3             |        P=0.098          (e)              P=0.187          P=0.523          P=0.236          P=0.222         | 
|POLY 1.5           |        P=0.108          (e)              P=0.203          P=0.523          P=0.237          P=0.229         | 
|POLY 6             |        P=0.089          (e)              P=0.175          P=0.521          P=0.234          P=0.215         | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.207          P=0.557          P=0.280          P=0.257         | 
|COCH-ARM / FISHERS |        P=0.119          (e)              P=0.241          P=0.517          P=0.241          P=0.241         | 
|ORDER RESTRICTED   |        P=0.136          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        1/13.08          0/12.09          0/9.99           0/10.85          0/13.80          0/9.94          | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.437N         P=0.519N         P=0.540N         P=0.540N         P=0.500N         P=0.564N        | 
|POLY 3             |        P=0.332N         P=0.516N         P=0.553N         P=0.537N         P=0.489N         P=0.554N        | 
|POLY 1.5           |        P=0.359N         P=0.513N         P=0.545N         P=0.526N         P=0.497N         P=0.544N        | 
|POLY 6             |        P=0.314N         P=0.520N         P=0.557N         P=0.542N         P=0.483N         P=0.560N        | 
|LOGISTIC REGRESSION|        P=0.437N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.420N         P=0.517N         P=0.517N         P=0.500N         P=0.517N         P=0.517N        | 
|ORDER RESTRICTED   |        P=0.112N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 2       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/15 (7%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/12.59          0/14.31          2/11.64          0/13.78          1/13.57          1/12.09         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             17.2%            0.0%             7.4%             8.3%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              138              ---              138              271             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.375          (e)              P=0.212          (e)              P=0.500          P=0.483         | 
|POLY 3             |        P=0.326          (e)              P=0.211          (e)              P=0.515          P=0.492         | 
|POLY 1.5           |        P=0.344          (e)              P=0.216          (e)              P=0.510          P=0.497         | 
|POLY 6             |        P=0.314          (e)              P=0.211          (e)              P=0.518          P=0.488         | 
|LOGISTIC REGRESSION|        P=0.354          (e)              P=0.302          (e)              P=0.483          P=0.487         | 
|COCH-ARM / FISHERS |        P=0.378          (e)              P=0.241          (e)              P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.328          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/13.08          0/12.12          0/10.06          1/11.80          0/13.80          1/10.04         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             8.5%             0.0%             10.0%           | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              97               ---              269             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.203          (e)              (e)              P=0.500          (e)              P=0.443         | 
|POLY 3             |        P=0.204          (e)              (e)              P=0.480          (e)              P=0.448         | 
|POLY 1.5           |        P=0.208          (e)              (e)              P=0.487          (e)              P=0.460         | 
|POLY 6             |        P=0.204          (e)              (e)              P=0.476          (e)              P=0.442         | 
|LOGISTIC REGRESSION|        P=0.276          (e)              (e)              (e)              (e)              P=0.443         | 
|COCH-ARM / FISHERS |        P=0.230          (e)              (e)              P=0.500          (e)              P=0.500         | 
|ORDER RESTRICTED   |        P=0.139          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 3       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/12.59          2/14.31          0/10.20          0/13.78          1/12.70          0/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             14.0%            0.0%             0.0%             7.9%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       0/8 (0%)         0/12 (0%)        1/11 (9%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              274 (T)          ---              ---              274 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.428N         P=0.300          (e)              (e)              P=0.540          (e)             | 
|POLY 3             |        P=0.404N         P=0.261          (e)              (e)              P=0.502          (e)             | 
|POLY 1.5           |        P=0.410N         P=0.254          (e)              (e)              P=0.501          (e)             | 
|POLY 6             |        P=0.400N         P=0.267          (e)              (e)              P=0.503          (e)             | 
|LOGISTIC REGRESSION|        (e)              P=0.300          (e)              (e)              P=0.540          (e)             | 
|COCH-ARM / FISHERS |        P=0.436N         P=0.241          (e)              (e)              P=0.500          (e)             | 
|ORDER RESTRICTED   |        P=0.312N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        3/15 (20%)       1/15 (7%)        0/15 (0%)        2/15 (13%)       0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/13.08          3/12.74          1/10.06          0/10.85          2/13.80          0/9.98          | 
|POLY-3 PERCENT (g) |        7.7%             23.5%            9.9%             0.0%             14.5%            0.0%            | 
|TERMINAL (d)       |        1/11 (9%)        2/10 (20%)       1/9 (11%)        0/9 (0%)         2/11 (18%)       0/8 (0%)        | 
|FIRST INCIDENCE    |        275 (T)          198              275 (T)          ---              275 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.255N         P=0.270          P=0.720          P=0.540N         P=0.500          P=0.564N        | 
|POLY 3             |        P=0.244N         P=0.286          P=0.700          P=0.537N         P=0.519          P=0.553N        | 
|POLY 1.5           |        P=0.237N         P=0.288          P=0.715          P=0.526N         P=0.507          P=0.540N        | 
|POLY 6             |        P=0.245N         P=0.285          P=0.694          P=0.542N         P=0.530          P=0.560N        | 
|LOGISTIC REGRESSION|        P=0.232N         P=0.288          P=0.720          (e)              P=0.500          (e)             | 
|COCH-ARM / FISHERS |        P=0.212N         P=0.299          P=0.759N         P=0.500N         P=0.500          P=0.500N        | 
|ORDER RESTRICTED   |        P=0.200N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 4       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/15 (53%)       5/15 (33%)       2/15 (13%)       5/15 (33%)       6/15 (40%)       6/15 (40%)      | 
|POLY-3 RATE (b)    |        8/12.69          5/14.31          2/10.23          5/13.81          6/12.70          6/12.78         | 
|POLY-3 PERCENT (g) |        63.0%            34.9%            19.6%            36.2%            47.3%            47.0%           | 
|TERMINAL (d)       |        5/9 (56%)        5/12 (42%)       1/8 (13%)        4/12 (33%)       6/11 (55%)       5/10 (50%)      | 
|FIRST INCIDENCE    |        271              274 (T)          271              271              274 (T)          180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.450          P=0.100N         P=0.068N         P=0.122N         P=0.241N         P=0.318N        | 
|POLY 3             |        P=0.456          P=0.139N         P=0.039N*        P=0.157N         P=0.344N         P=0.338N        | 
|POLY 1.5           |        P=0.461          P=0.159N         P=0.029N*        P=0.171N         P=0.348N         P=0.333N        | 
|POLY 6             |        P=0.449          P=0.127N         P=0.049N*        P=0.153N         P=0.344N         P=0.346N        | 
|LOGISTIC REGRESSION|        P=0.377          P=0.115N         P=0.054N         P=0.148N         P=0.349N         P=0.393N        | 
|COCH-ARM / FISHERS |        P=0.442          P=0.231N         P=0.025N*        P=0.231N         P=0.358N         P=0.358N        | 
|ORDER RESTRICTED   |        P=0.161N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       9/15 (60%)       4/15 (27%)       7/15 (47%)       7/15 (47%)       5/15 (33%)      | 
|POLY-3 RATE (b)    |        4/13.08          9/12.82          4/10.06          7/11.59          7/13.94          5/10.68         | 
|POLY-3 PERCENT (g) |        30.6%            70.2%            39.8%            60.4%            50.2%            46.8%           | 
|TERMINAL (d)       |        4/11 (36%)       7/10 (70%)       4/9 (44%)        5/9 (56%)        5/11 (46%)       4/8 (50%)       | 
|FIRST INCIDENCE    |        275 (T)          192              275 (T)          184              267              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.448          P=0.049 *        P=0.536          P=0.126          P=0.242          P=0.282         | 
|POLY 3             |        P=0.539          P=0.042 *        P=0.493          P=0.136          P=0.261          P=0.352         | 
|POLY 1.5           |        P=0.547          P=0.046 *        P=0.532          P=0.156          P=0.235          P=0.382         | 
|POLY 6             |        P=0.555          P=0.040 *        P=0.474          P=0.133          P=0.288          P=0.345         | 
|LOGISTIC REGRESSION|        P=0.524          P=0.040 *        P=0.536          P=0.116          P=0.284          P=0.321         | 
|COCH-ARM / FISHERS |        P=0.484N         P=0.070          P=0.659N         P=0.225          P=0.225          P=0.500         | 
|ORDER RESTRICTED   |        P=0.219          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 5       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tooth                                                                                                                            | 
|     Odontogenic Tumor                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/15 (20%)       4/15 (27%)       2/15 (13%)       2/15 (13%)       2/15 (13%)       6/15 (40%)      | 
|POLY-3 RATE (b)    |        3/13.64          4/15.00          2/10.23          2/13.81          2/12.83          6/14.14         | 
|POLY-3 PERCENT (g) |        22.0%            26.7%            19.6%            14.5%            15.6%            42.4%           | 
|TERMINAL (d)       |        0/9 (0%)         1/12 (8%)        1/8 (13%)        1/12 (8%)        1/11 (9%)        2/10 (20%)      | 
|FIRST INCIDENCE    |        76               198              271              271              261              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.119          P=0.587          P=0.589N         P=0.452N         P=0.498N         P=0.244         | 
|POLY 3             |        P=0.128          P=0.556          P=0.635N         P=0.494N         P=0.529N         P=0.230         | 
|POLY 1.5           |        P=0.122          P=0.535          P=0.598N         P=0.496N         P=0.526N         P=0.220         | 
|POLY 6             |        P=0.135          P=0.576          P=0.658N         P=0.494N         P=0.527N         P=0.245         | 
|LOGISTIC REGRESSION|        P=0.114          P=0.317          P=0.487N         P=0.611N         P=0.503N         P=0.211         | 
|COCH-ARM / FISHERS |        P=0.112          P=0.500          P=0.500N         P=0.500N         P=0.500N         P=0.213         | 
|ORDER RESTRICTED   |        P=0.128          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tooth                                                                                                                            | 
|     Odontogenic Tumor                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       4/15 (27%)       2/15 (13%)       5/15 (33%)       5/15 (33%)       1/15 (7%)       | 
|POLY-3 RATE (b)    |        4/15.00          4/12.74          2/11.25          5/13.16          5/14.00          1/10.68         | 
|POLY-3 PERCENT (g) |        26.7%            31.4%            17.8%            38.0%            35.7%            9.4%            | 
|TERMINAL (d)       |        0/11 (0%)        2/10 (20%)       0/9 (0%)         1/9 (11%)        2/11 (18%)       0/8 (0%)        | 
|FIRST INCIDENCE    |        109              206              200              165              267              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.275N         P=0.588          P=0.461N         P=0.399          P=0.516          P=0.290N        | 
|POLY 3             |        P=0.296N         P=0.556          P=0.475N         P=0.409          P=0.452          P=0.287N        | 
|POLY 1.5           |        P=0.263N         P=0.586          P=0.446N         P=0.429          P=0.453          P=0.253N        | 
|POLY 6             |        P=0.317N         P=0.531          P=0.485N         P=0.401          P=0.452          P=0.309N        | 
|LOGISTIC REGRESSION|        P=0.161N         P=0.615N         P=0.177N         P=0.626N         P=0.500          P=0.062N        | 
|COCH-ARM / FISHERS |        P=0.176N         P=0.659N         P=0.326N         P=0.500          P=0.500          P=0.165N        | 
|ORDER RESTRICTED   |        P=0.228N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 6       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Leukemia: Erythrocytic                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        1/15 (7%)        2/15 (13%)       0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/13.22          0/14.31          1/10.83          2/14.97          0/12.70          0/12.06         | 
|POLY-3 PERCENT (g) |        7.6%             0.0%             9.2%             13.4%            0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        197              ---              197              199              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.284N         P=0.471N         P=0.727          P=0.560          P=0.500N         P=0.516N        | 
|POLY 3             |        P=0.296N         P=0.484N         P=0.716          P=0.544          P=0.508N         P=0.518N        | 
|POLY 1.5           |        P=0.285N         P=0.487N         P=0.730          P=0.533          P=0.505N         P=0.509N        | 
|POLY 6             |        P=0.305N         P=0.483N         P=0.707          P=0.552          P=0.511N         P=0.527N        | 
|LOGISTIC REGRESSION|        P=0.271N         P=0.668N         P=0.722N         P=0.284          P=0.505N         P=0.527N        | 
|COCH-ARM / FISHERS |        P=0.267N         P=0.500N         P=0.759N         P=0.500          P=0.500N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.361N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Leukemia: Erythrocytic                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        3/15 (20%)       1/15 (7%)        0/15 (0%)        0/15 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        1/14.01          3/13.98          1/10.91          0/10.85          0/13.80          1/10.50         | 
|POLY-3 PERCENT (g) |        7.1%             21.5%            9.2%             0.0%             0.0%             9.5%            | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        109              192              148              ---              ---              215             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.364N         P=0.289          P=0.727          P=0.514N         P=0.514N         P=0.706         | 
|POLY 3             |        P=0.293N         P=0.296          P=0.703          P=0.550N         P=0.503N         P=0.693         | 
|POLY 1.5           |        P=0.307N         P=0.290          P=0.714          P=0.536N         P=0.507N         P=0.708         | 
|POLY 6             |        P=0.282N         P=0.308          P=0.699          P=0.557N         P=0.499N         P=0.690         | 
|LOGISTIC REGRESSION|        P=0.239N         P=0.366          P=0.512N         P=0.337N         P=0.341N         P=0.607N        | 
|COCH-ARM / FISHERS |        P=0.322N         P=0.299          P=0.759N         P=0.500N         P=0.500N         P=0.759N        | 
|ORDER RESTRICTED   |        P=0.281N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 7       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/15 (53%)       6/15 (40%)       3/15 (20%)       5/15 (33%)       8/15 (53%)       8/15 (53%)      | 
|POLY-3 RATE (b)    |        8/12.69          6/14.31          3/10.23          5/13.81          8/12.70          8/12.78         | 
|POLY-3 PERCENT (g) |        63.0%            41.9%            29.3%            36.2%            63.0%            62.6%           | 
|TERMINAL (d)       |        5/9 (56%)        6/12 (50%)       2/8 (25%)        4/12 (33%)       8/11 (73%)       7/10 (70%)      | 
|FIRST INCIDENCE    |        271              274 (T)          271              271              274 (T)          180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.182          P=0.163N         P=0.138N         P=0.122N         P=0.475N         P=0.568N        | 
|POLY 3             |        P=0.167          P=0.239N         P=0.111N         P=0.157N         P=0.659N         P=0.651N        | 
|POLY 1.5           |        P=0.177          P=0.267N         P=0.087N         P=0.171N         P=0.653N         P=0.635N        | 
|POLY 6             |        P=0.158          P=0.223N         P=0.133N         P=0.153N         P=0.661          P=0.658         | 
|LOGISTIC REGRESSION|        P=0.114          P=0.199N         P=0.135N         P=0.148N         P=0.649          P=0.597         | 
|COCH-ARM / FISHERS |        P=0.179          P=0.358N         P=0.064N         P=0.231N         P=0.642N         P=0.642N        | 
|ORDER RESTRICTED   |        P=0.277          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       11/15 (73%)      5/15 (33%)       7/15 (47%)       8/15 (53%)       5/15 (33%)      | 
|POLY-3 RATE (b)    |        4/13.08          11/13.45         5/10.06          7/11.59          8/13.94          5/10.68         | 
|POLY-3 PERCENT (g) |        30.6%            81.8%            49.7%            60.4%            57.4%            46.8%           | 
|TERMINAL (d)       |        4/11 (36%)       8/10 (80%)       5/9 (56%)        5/9 (56%)        6/11 (55%)       4/8 (50%)       | 
|FIRST INCIDENCE    |        275 (T)          192              275 (T)          184              267              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.562N         P=0.011 *        P=0.346          P=0.126          P=0.146          P=0.282         | 
|POLY 3             |        P=0.459N         P=0.005 **       P=0.310          P=0.136          P=0.153          P=0.352         | 
|POLY 1.5           |        P=0.448N         P=0.005 **       P=0.353          P=0.156          P=0.133          P=0.382         | 
|POLY 6             |        P=0.445N         P=0.006 **       P=0.289          P=0.133          P=0.175          P=0.345         | 
|LOGISTIC REGRESSION|        P=0.477N         P=0.008 **       P=0.346          P=0.116          P=0.175          P=0.321         | 
|COCH-ARM / FISHERS |        P=0.354N         P=0.013 *        P=0.500          P=0.225          P=0.132          P=0.500         | 
|ORDER RESTRICTED   |        P=0.115          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 8       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        4/15 (27%)       2/15 (13%)       2/15 (13%)       2/15 (13%)      | 
|POLY-3 RATE (b)    |        1/13.22          0/14.31          4/12.30          2/14.97          2/13.91          2/12.70         | 
|POLY-3 PERCENT (g) |        7.6%             0.0%             32.5%            13.4%            14.4%            15.7%           | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        197              ---              138              199              138              200             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.406          P=0.471N         P=0.135          P=0.560          P=0.509          P=0.481         | 
|POLY 3             |        P=0.371          P=0.484N         P=0.136          P=0.544          P=0.518          P=0.486         | 
|POLY 1.5           |        P=0.390          P=0.487N         P=0.141          P=0.533          P=0.513          P=0.494         | 
|POLY 6             |        P=0.361          P=0.483N         P=0.136          P=0.552          P=0.523          P=0.479         | 
|LOGISTIC REGRESSION|        P=0.428          P=0.668N         P=0.221          P=0.284          P=0.496          P=0.493         | 
|COCH-ARM / FISHERS |        P=0.426          P=0.500N         P=0.165          P=0.500          P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.242          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        3/15 (20%)       1/15 (7%)        2/15 (13%)       0/15 (0%)        2/15 (13%)      | 
|POLY-3 RATE (b)    |        1/14.01          3/13.98          1/10.91          2/11.80          0/13.80          2/10.56         | 
|POLY-3 PERCENT (g) |        7.1%             21.5%            9.2%             16.9%            0.0%             18.9%           | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         1/9 (11%)        0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        109              192              148              97               ---              215             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.579          P=0.289          P=0.727          P=0.469          P=0.514N         P=0.411         | 
|POLY 3             |        P=0.564N         P=0.296          P=0.703          P=0.439          P=0.503N         P=0.400         | 
|POLY 1.5           |        P=0.573N         P=0.290          P=0.714          P=0.457          P=0.507N         P=0.420         | 
|POLY 6             |        P=0.554N         P=0.308          P=0.699          P=0.430          P=0.499N         P=0.398         | 
|LOGISTIC REGRESSION|        P=0.465N         P=0.366          P=0.512N         P=0.762          P=0.341N         P=0.644         | 
|COCH-ARM / FISHERS |        P=0.564N         P=0.299          P=0.759N         P=0.500          P=0.500N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.351          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/03                           EXPERIMENT: 99033 TEST: 01                                            Page 9       
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC)       -        TRANSGENIC MODEL EVALUATION II (ASPA   
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/15 (67%)      9/15 (60%)       7/15 (47%)       8/15 (53%)       11/15 (73%)      11/15 (73%)     | 
|POLY-3 RATE (b)    |        10/14.30         9/15.00          7/12.30          8/15.00          11/14.04         11/14.14        | 
|POLY-3 PERCENT (g) |        69.9%            60.0%            56.9%            53.3%            78.3%            77.8%           | 
|TERMINAL (d)       |        5/9 (56%)        6/12 (50%)       3/8 (38%)        5/12 (42%)       8/11 (73%)       7/10 (70%)      | 
|FIRST INCIDENCE    |        76               198              138              199              138              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.213          P=0.273N         P=0.426N         P=0.214N         P=0.589N         P=0.546         | 
|POLY 3             |        P=0.146          P=0.432N         P=0.387N         P=0.296N         P=0.468          P=0.480         | 
|POLY 1.5           |        P=0.148          P=0.456N         P=0.351N         P=0.318N         P=0.459          P=0.479         | 
|POLY 6             |        P=0.147          P=0.411N         P=0.395N         P=0.279N         P=0.489          P=0.491         | 
|LOGISTIC REGRESSION|        P=0.153          P=0.566N         P=0.251N         P=0.416N         P=0.501          P=0.500         | 
|COCH-ARM / FISHERS |        P=0.155          P=0.500N         P=0.231N         P=0.355N         P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.278          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |        #                #                #                #                #                #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/15 (53%)       12/15 (80%)      8/15 (53%)       11/15 (73%)      11/15 (73%)      7/15 (47%)      | 
|POLY-3 RATE (b)    |        8/15.00          12/14.03         8/12.10          11/14.12         11/14.00         7/11.26         | 
|POLY-3 PERCENT (g) |        53.3%            85.6%            66.1%            77.9%            78.6%            62.1%           | 
|TERMINAL (d)       |        4/11 (36%)       8/10 (80%)       5/9 (56%)        6/9 (67%)        8/11 (73%)       4/8 (50%)       | 
|FIRST INCIDENCE    |        109              192              148              97               267              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.494N         P=0.144          P=0.415          P=0.164          P=0.298          P=0.463         | 
|POLY 3             |        P=0.541          P=0.065          P=0.393          P=0.157          P=0.150          P=0.480         | 
|POLY 1.5           |        P=0.496N         P=0.071          P=0.431          P=0.173          P=0.151          P=0.545         | 
|POLY 6             |        P=0.509          P=0.064          P=0.385          P=0.151          P=0.150          P=0.456         | 
|LOGISTIC REGRESSION|        P=0.296N         P=0.128          P=0.615          P=0.313          P=0.224          P=0.586N        | 
|COCH-ARM / FISHERS |        P=0.231N         P=0.123          P=0.642N         P=0.225          P=0.225          P=0.500N        | 
|ORDER RESTRICTED   |        P=0.211          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
                                                                                                                                   
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.