https://ntp.niehs.nih.gov/go/10284

TDMS Study 99033-03 Pathology Tables

NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/05/03       
EXPERIMENT: 99033 TEST: 03                                                                                     TIME: 11:45:00       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: 99033B       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
------------------------------------------------------------------------------------------------------------------------------------
                                                        FINAL #3 TG:P16 MICE                                                        
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/05/03       
EXPERIMENT: 99033 TEST: 03                                                                                     TIME: 11:45:00       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: 99033B       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE MICE                                                                                      
                       FIRST TERMINAL SACRIFICE AT 274 DAYS                                                                         
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                          DOSE = VEHICLE CONTROL                                |                                                 
 |                       ----------------------------                             |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 1      CENSORED DEATHS 0    TERMINAL 14        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      63                                                                        |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 3125 PPM                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 1      CENSORED DEATHS 0    TERMINAL 14        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      232                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 6250 PPM                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 0      CENSORED DEATHS 0    TERMINAL 15        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |     NONE                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE MICE                                                                                      
                       FIRST TERMINAL SACRIFICE AT 274 DAYS                                                                         
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 12500   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 1      CENSORED DEATHS 0    TERMINAL 14        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      44                                                                        |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 25000   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 1      CENSORED DEATHS 0    TERMINAL 14        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      22                                                                        |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 50000   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 0      CENSORED DEATHS 0    TERMINAL 15        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |     NONE                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE MICE                                                                                      
                       FIRST TERMINAL SACRIFICE AT 274 DAYS                                                                         
 ==================================================================================                                                 
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |    DOSE                               TIME (DAYS)                              |                                                 
 |                 28    56    84   112   140   168   196   224   252   274 (A)   |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |           |                                                                    |                                                 
 |VEHICLE    |   100.0 100.0  93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3      |                                                 
 |CONTROL    |                                                                    |                                                 
 |           |                                                                    |                                                 
 |3125 PPM   |   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0  93.3  93.3      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |6250 PPM   |   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |12500   PPM|   100.0  93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |25000   PPM|    93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3  93.3      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |50000   PPM|   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE MICE                                                                                      
                       FIRST TERMINAL SACRIFICE AT 274 DAYS                                                                         
 ===============================================================================================================================    
 |                                               SURVIVAL SUMMARY STATISTICS                                                   |    
 |                                                                                                                             |    
 |                                                                                                                             |    
 |-----------------------------------------------------------------------------------------------------------------------------|    
 |                                                                          DOSE                                               |    
 |                                                                                                                             |    
 |                                VEHICLE         3125 PPM        6250 PPM        12500   PPM     25000   PPM     50000   PPM  |    
 |                                CONTROL                                                                                      |    
 |-----------------------------------------------------------------------------------------------------------------------------|    
 |SURVIVAL AT END OF STUDY|       93.3%           93.3%          100.0%           93.3%           93.3%          100.0%        |    
 |(KAPLAN-MEIER)          |                                                                                                    |    
 |                        |                                                                                                    |    
 |SIGNIFICANCE (B)        |       P=0.741N        P=1.000N        P=1.000N        P=1.000         P=1.000         P=1.000N     |    
 |(LIFE TABLE)            |                                                                                                    |    
 |                        |                                                                                                    |    
 |MEAN DAY OF             |        63.0           232.0              .             44.0            22.0              .         |    
 |NATURAL DEATHS (C)      |       (  . )          (  . )          (  . )          (  . )          (  . )          (  . )       |    
 |(STANDARD ERROR)        |                                                                                                    |    
 |                        |                                                                                                    |    
 |MEAN LIFE SPAN (D)      |       259.9           271.2           274.0           258.7           257.2           274.0        |    
 |(STANDARD ERROR)        |       (14.1)          ( 2.8)          ( 0.0)          (15.3)          (16.8)          ( 0.0)       |    
 |                        |                                                                                                    |    
 ===============================================================================================================================    
       (A)  FIRST TERMINAL SACRIFICE                                                                                                
       (B)  THE FIRST ENTRY IS THE TREND TEST (TARONE, 1975) RESULT.                                                                
            SUBSEQUENT ENTRIES ARE THE RESULTS OF PAIRWISE TESTS                                                                    
            (COX,1972).  NEGATIVE TRENDS ARE INDICATED BY "N".                                                                      
       (C)  MEAN OF ALL UNCENSORED DEATHS PRIOR TO TERMINAL SACRIFICE                                                               
       (D)  MEAN OF ALL DEATHS (UNCENSORED, CENSORED, TERMINAL SACRIFICE)                                                           
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE MICE                                                                                     
                       FIRST TERMINAL SACRIFICE AT 275 DAYS                                                                         
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                          DOSE = VEHICLE CONTROL                                |                                                 
 |                       ----------------------------                             |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 2      CENSORED DEATHS 0    TERMINAL 13        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      13    219                                                                 |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 3125 PPM                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 0      CENSORED DEATHS 0    TERMINAL 15        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |     NONE                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 6250 PPM                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 2      CENSORED DEATHS 0    TERMINAL 13        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      108   216                                                                 |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE MICE                                                                                     
                       FIRST TERMINAL SACRIFICE AT 275 DAYS                                                                         
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 12500   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 0      CENSORED DEATHS 0    TERMINAL 15        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |     NONE                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 25000   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 0      CENSORED DEATHS 0    TERMINAL 15        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |     NONE                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 50000   PPM                              |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 15     UNCENSORED DEATHS 1      CENSORED DEATHS 0    TERMINAL 14        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      267                                                                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE MICE                                                                                     
                       FIRST TERMINAL SACRIFICE AT 275 DAYS                                                                         
 ==================================================================================                                                 
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |    DOSE                               TIME (DAYS)                              |                                                 
 |                 28    56    84   112   140   168   196   224   252   275 (A)   |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |           |                                                                    |                                                 
 |VEHICLE    |    93.3  93.3  93.3  93.3  93.3  93.3  93.3  86.7  86.7  86.7      |                                                 
 |CONTROL    |                                                                    |                                                 
 |           |                                                                    |                                                 
 |3125 PPM   |   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |6250 PPM   |   100.0 100.0 100.0  93.3  93.3  93.3  93.3  86.7  86.7  86.7      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |12500   PPM|   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |25000   PPM|   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |50000   PPM|   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0  93.3      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 ==================================================================================                                                 
                    TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                                                      
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE MICE                                                                                     
                       FIRST TERMINAL SACRIFICE AT 275 DAYS                                                                         
 ===============================================================================================================================    
 |                                               SURVIVAL SUMMARY STATISTICS                                                   |    
 |                                                                                                                             |    
 |                                                                                                                             |    
 |-----------------------------------------------------------------------------------------------------------------------------|    
 |                                                                          DOSE                                               |    
 |                                                                                                                             |    
 |                                VEHICLE         3125 PPM        6250 PPM        12500   PPM     25000   PPM     50000   PPM  |    
 |                                CONTROL                                                                                      |    
 |-----------------------------------------------------------------------------------------------------------------------------|    
 |SURVIVAL AT END OF STUDY|       86.7%          100.0%           86.7%          100.0%          100.0%           93.3%        |    
 |(KAPLAN-MEIER)          |                                                                                                    |    
 |                        |                                                                                                    |    
 |SIGNIFICANCE (B)        |       P=0.851N        P=0.464N        P=1.000         P=0.464N        P=0.464N        P=0.951N     |    
 |(LIFE TABLE)            |                                                                                                    |    
 |                        |                                                                                                    |    
 |MEAN DAY OF             |       116.0              .            162.0              .               .            267.0        |    
 |NATURAL DEATHS (C)      |       ( 103)          (  . )          (54.0)          (  . )          (  . )          (  . )       |    
 |(STANDARD ERROR)        |                                                                                                    |    
 |                        |                                                                                                    |    
 |MEAN LIFE SPAN (D)      |       253.8           275.0           259.9           275.0           275.0           274.5        |    
 |(STANDARD ERROR)        |       (17.6)          ( 0.0)          (11.5)          ( 0.0)          ( 0.0)          ( 0.5)       |    
 |                        |                                                                                                    |    
 ===============================================================================================================================    
       (A)  FIRST TERMINAL SACRIFICE                                                                                                
       (B)  THE FIRST ENTRY IS THE TREND TEST (TARONE, 1975) RESULT.                                                                
            SUBSEQUENT ENTRIES ARE THE RESULTS OF PAIRWISE TESTS                                                                    
            (COX,1972).  NEGATIVE TRENDS ARE INDICATED BY "N".                                                                      
       (C)  MEAN OF ALL UNCENSORED DEATHS PRIOR TO TERMINAL SACRIFICE                                                               
       (D)  MEAN OF ALL DEATHS (UNCENSORED, CENSORED, TERMINAL SACRIFICE)                                                           
                                             TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                             
                                                    KAPLAN-MEIER SURVIVAL CURVES                                                    
                                                        VEHICLE CONTROL  = 1                                                        
                                                        3125 PPM         = 2                                                        
                                                        6250 PPM         = 3                                                        
                                                        12500   PPM      = 4                                                        
                                                        25000   PPM      = 5                                                        
                                                        50000   PPM      = 6                                                        
------------------------------------------------------ SPECIES=MICE SEX=MALE -------------------------------------------------------
                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.                                           
                (NOTE: 9 obs hidden.)                                                                                               
      P        |                                                                                                                    
      E        |                                                                                                                    
      R 100.00 +  1         5       4    1                                                                2               3         
      C        |                                                                                                                    
      E        |                                                                                                                    
      N        |                                                                                                                    
      T  93.33 +            5       4    1                                                                2               1         
               |                                                                                                                    
      S        ---+------------+------------+------------+------------+------------+------------+------------+------------+--       
      U           0            5           10           15           20           25           30           35           40         
      R                                                                                                                             
                                                                    WEEK                                                            
                                             TRANSGENIC MODEL EVALUATION II (ASPARTAME)                                             
                                                    KAPLAN-MEIER SURVIVAL CURVES                                                    
                                                        VEHICLE CONTROL  = 1                                                        
                                                        3125 PPM         = 2                                                        
                                                        6250 PPM         = 3                                                        
                                                        12500   PPM      = 4                                                        
                                                        25000   PPM      = 5                                                        
                                                        50000   PPM      = 6                                                        
----------------------------------------------------- SPECIES=MICE SEX=FEMALE ------------------------------------------------------
                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.                                           
          (NOTE: 8 obs hidden.)                                                                                                     
P        |                                                                                                                          
E        |                                                                                                                          
R 100.00 +1     1                                         3                                                                    6  2 
C        |                                                                                                                          
E        |                                                                                                                          
N        |                                                                                                                          
T  93.33 +      1                                         3                                            3  1                    6  6 
         |                                                                                                                          
S        |                                                                                                                          
U        |                                                                                                                          
R  86.67 +                                                                                             3  1                       1 
V        |                                                                                                                          
I        -+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+-
V         0  1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 
A                                                                                                                                   
                                                                     WEEK