National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20962

TDMS Study 91005-07 Pathology Tables

NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 03/25/05       
EXPERIMENT: 91005 TEST: 07                                                                                     TIME: 10:15:16       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: HERSCHELL, GILES                                                                                  CAS: 7220-79-3       
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           FINAL #1 RATS                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 03/25/05       
EXPERIMENT: 91005 TEST: 07                                                                                     TIME: 10:15:16       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: HERSCHELL, GILES                                                                                  CAS: 7220-79-3       
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE RATS                                                                                      
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
                                                                                                                                    
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 0 MG/KG                                  |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 19     CENSORED DEATHS 0    TERMINAL 31        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      453   544   563   586   586   616   620   641   642   645                 |                                                 
 |      649   662   662   675   685   694   694   702   712                       |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 5 MG/KG                                  |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 17     CENSORED DEATHS 0    TERMINAL 33        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      473   540   540   561   568   576   582   590   652   652                 |                                                 
 |      673   673   682   712   720   722   723                                   |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 25 MG/KG                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 10     CENSORED DEATHS 1    TERMINAL 39        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      586   619   619   637   649   690   690   710   712   726                 |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      489                                                                       |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE RATS                                                                                      
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
                                                                                                                                    
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 50 MG/KG                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 17     CENSORED DEATHS 2    TERMINAL 31        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      401   465   504   530   563   576   597   626   626   652                 |                                                 
 |      658   666   687   692   703   715   717                                   |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      191   508                                                                 |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                     MALE RATS                                                                                      
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
 ==================================================================================                                                 
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |    DOSE                               TIME (DAYS)                              |                                                 
 |                 90   180   270   365   425   485   545   605   665   729 (A)   |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |           |                                                                    |                                                 
 |0 MG/KG    |   100.0 100.0 100.0 100.0 100.0  98.0  96.0  90.0  74.0  62.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |5 MG/KG    |   100.0 100.0 100.0 100.0 100.0  98.0  94.0  84.0  80.0  66.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |25 MG/KG   |   100.0 100.0 100.0 100.0 100.0 100.0 100.0  98.0  89.8  79.6      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |50 MG/KG   |   100.0 100.0 100.0 100.0  98.0  95.9  91.8  85.5  77.2  64.7      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 ==================================================================================                                                 
 ==================================================================================                                                 
 |                           SURVIVAL SUMMARY STATISTICS                          |                                                 
 |                                                                                |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                                  DOSE                          |                                                 
 |                                                                                |                                                 
 |                                0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |SURVIVAL AT END OF STUDY|       62.0%        66.0%        79.6%        64.7%    |                                                 
 |(KAPLAN-MEIER)          |                                                       |                                                 
 |                        |                                                       |                                                 
 |SIGNIFICANCE (B)        |       P=0.750N     P=0.813N     P=0.067N     P=0.957N |                                                 
 |(LIFE TABLE)            |                                                       |                                                 
 |                        |                                                       |                                                 
 |MEAN DAY OF             |       633.2        625.8        663.8        610.5    |                                                 
 |NATURAL DEATHS (C)      |       (14.8)       (18.7)       (15.2)       (22.5)   |                                                 
 |(STANDARD ERROR)        |                                                       |                                                 
 |                        |                                                       |                                                 
 |MEAN LIFE SPAN (D)      |       692.6        693.9        711.2        673.5    |                                                 
 |(STANDARD ERROR)        |       ( 8.7)       ( 9.4)       ( 6.5)       (15.1)   |                                                 
 |                        |                                                       |                                                 
 ==================================================================================                                                 
                                                                                                                                    
       (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)                                                           
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE RATS                                                                                     
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
                                                                                                                                    
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 0 MG/KG                                  |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 15     CENSORED DEATHS 0    TERMINAL 35        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      344   516   563   591   638   640   648   648   652   652                 |                                                 
 |      652   668   674   698   710                                               |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 5 MG/KG                                  |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 49     UNCENSORED DEATHS 17     CENSORED DEATHS 0    TERMINAL 32        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      395   568   576   585   621   628   641   644   648   663                 |                                                 
 |      677   687   694   702   702   702   710                                   |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                DOSE = 25 MG/KG                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 14     CENSORED DEATHS 0    TERMINAL 36        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      492   521   540   557   560   563   593   596   596   646                 |                                                 
 |      651   687   702   723                                                     |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      NONE                                                                      |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE RATS                                                                                     
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
                                                                                                                                    
                          INDIVIDUAL SURVIVAL TIMES (DAYS)                                                                          
 ==================================================================================                                                 
 |                                DOSE = 50 MG/KG                                 |                                                 
 |                             ---------------------                              |                                                 
 |                                                                                |                                                 
 |  TOTAL 50     UNCENSORED DEATHS 14     CENSORED DEATHS 1    TERMINAL 35        |                                                 
 |                                                                                |                                                 
 |  UNCENSORED DEATHS                                                             |                                                 
 |      223   239   284   312   349   509   527   544   568   573                 |                                                 
 |      677   677   687   725                                                     |                                                 
 |  CENSORED DEATHS                                                               |                                                 
 |      480                                                                       |                                                 
 |                                                                                |                                                 
 ==================================================================================                                                 
                                                                                                                                   
                             METHYLENE BLUE TRIHYDRATE                                                                              
                       STATISTICAL ANALYSIS OF SURVIVAL DATA                                                                        
                                    FEMALE RATS                                                                                     
                       FIRST TERMINAL SACRIFICE AT 729 DAYS                                                                         
 ==================================================================================                                                 
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |    DOSE                               TIME (DAYS)                              |                                                 
 |                 90   180   270   365   425   485   545   605   665   729 (A)   |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |           |                                                                    |                                                 
 |0 MG/KG    |   100.0 100.0 100.0  98.0  98.0  98.0  96.0  92.0  78.0  70.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |5 MG/KG    |   100.0 100.0 100.0 100.0  98.0  98.0  98.0  91.8  79.6  65.3      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |25 MG/KG   |   100.0 100.0 100.0 100.0 100.0 100.0  94.0  82.0  78.0  72.0      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 |50 MG/KG   |   100.0 100.0  96.0  90.0  90.0  90.0  83.9  79.8  79.8  71.6      |                                                 
 |           |                                                                    |                                                 
 |           |                                                                    |                                                 
 ==================================================================================                                                 
 ==================================================================================                                                 
 |                           SURVIVAL SUMMARY STATISTICS                          |                                                 
 |                                                                                |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |                                                  DOSE                          |                                                 
 |                                                                                |                                                 
 |                                0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG |                                                 
 |                                                                                |                                                 
 |--------------------------------------------------------------------------------|                                                 
 |SURVIVAL AT END OF STUDY|       70.0%        65.3%        72.0%        71.6%    |                                                 
 |(KAPLAN-MEIER)          |                                                       |                                                 
 |                        |                                                       |                                                 
 |SIGNIFICANCE (B)        |       P=0.895N     P=0.806      P=1.000N     P=1.000  |                                                 
 |(LIFE TABLE)            |                                                       |                                                 
 |                        |                                                       |                                                 
 |MEAN DAY OF             |       619.6        637.8        601.9        492.4    |                                                 
 |NATURAL DEATHS (C)      |       (23.5)       (18.8)       (18.8)       (47.5)   |                                                 
 |(STANDARD ERROR)        |                                                       |                                                 
 |                        |                                                       |                                                 
 |MEAN LIFE SPAN (D)      |       696.2        697.4        693.4        657.8    |                                                 
 |(STANDARD ERROR)        |       ( 9.9)       ( 9.0)       ( 9.6)       (20.2)   |                                                 
 |                        |                                                       |                                                 
 ==================================================================================                                                 
                                                                                                                                    
       (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)                                                           
                                                                                                                                   
                                                     METHYLENE BLUE TRIHYDRATE                                                      
                                                    KAPLAN-MEIER SURVIVAL CURVES                                                    
                                                        0 MG/KG          = 1                                                        
                                                        5 MG/KG          = 2                                                        
                                                        25 MG/KG         = 3                                                        
                                                        50 MG/KG         = 4                                                        
                                                                                                                                    
------------------------------------------------------ SPECIES=RATS SEX=MALE -------------------------------------------------------
                                                                                                                                    
                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.                                           
                                                                                                                                    
      |                                                                                                                             
      |                                                                                                                             
  100 + 1                                                               4       1  2                3                               
      |                                                                                                                             
      |                                                                 4       1 42          1     3     3                         
      |                                                                           4    4      1  1                                  
   95 +                                                                                                                             
      |                                                                                4    4 2  1  1     3 3                       
      |                                                                                          22                                 
      |                                                                                     4    4          3 3                     
P  90 +                                                                                          4221    1    3      3              
E     |                                                                                                                             
R     |                                                                                            22  4 11                         
C     |                                                                                             2 2   1  1       3  3           
E  85 +                                                                                                4   4                        
N     |                                                                                               2        2                    
T     |                                                                                                      11                     
      |                                                                                                    4   4        3 3         
S  80 +                                                                                                        2   2      3 3       
U     |                                                                                                                             
R     |                                                                                                       14 14                 
V     |                                                                                                            22               
I  75 +                                                                                                           4  4              
V     |                                                                                                          1 12   2           
A     |                                                                                                            11   22          
L     |                                                                                                              4 4            
   70 +                                                                                                             1 1  22         
      |                                                                                                                4 4          
      |                                                                                                                             
      |                                                                                                               11  2 2       
   65 +                                                                                                                  4  4       
      |                                                                                                                11           
      |                                                                                                                 1   1       
      |                                                                                                                             
   60 +                                                                                                                             
      |                                                                                                                             
      --+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+--
        0         10         20         30         40         50         60         70         80         90         100        110 
                                                                                                                                    
                                                                   WEEK                                                             
                                                                                                                                    
NOTE: 7 obs hidden.                                                                                                                 
                                                                                                                                   
                                                     METHYLENE BLUE TRIHYDRATE                                                      
                                                    KAPLAN-MEIER SURVIVAL CURVES                                                    
                                                        0 MG/KG          = 1                                                        
                                                        5 MG/KG          = 2                                                        
                                                        25 MG/KG         = 3                                                        
                                                        50 MG/KG         = 4                                                        
                                                                                                                                    
----------------------------------------------------- SPECIES=RATS SEX=FEMALE ------------------------------------------------------
                                                                                                                                    
                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.                                           
                                                                                                                                    
      |                                                                                                                             
      |                                                                                                                             
  100 + 1                                  4                   1       2              3                                             
      |                                                                                                                             
      |                                    4   4               1       2              3  1 3      2                                 
      |                                        4     4                                   1 3  3  122                                
   95 +                                                                                                                             
      |                                              4    4                                   3 31 22 1                             
P     |                                                   4    4                                      1      1                      
E     |                                                                                             2     2                         
R  90 +                                                        4                        4       33        22                        
C     |                                                                                                                             
E     |                                                                                 4   4    3    3    2 11                     
N     |                                                                                     4 4       33                            
T  85 +                                                                                                                             
      |                                                                                       4   4          211                    
S     |                                                                                                3      3                     
U     |                                                                                                       2  2                  
R  80 +                                                                                           4              2 2                
V     |                                                                                                                             
I     |                                                                                                       31  12 2              
V     |                                                                                                           11 3 3            
A  75 +                                                                                                              22             
L     |                                                                                                            1 412  3         
      |                                                                                                               1 1 3 3       
      |                                                                                                                   4 4       
   70 +                                                                                                                 1   1       
      |                                                                                                                             
      |                                                                                                                22           
      |                                                                                                                             
   65 +                                                                                                                 2   2       
      |                                                                                                                             
      --+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+--
        0         10         20         30         40         50         60         70         80         90         100        110 
                                                                                                                                    
                                                                   WEEK                                                             
                                                                                                                                    
NOTE: 12 obs hidden.                                                                                                                
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.