National Toxicology Program

National Toxicology Program
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TR 395 Rat Pathology Tables

NTP           STATISTICAL ANALYSIS OF SURVIVAL DATA            REPORT: PEIRPT11 
LAB: Mason                                                     DATE: 09/04/94   
EXP: 05030                       PROBENECID                    TIME: 13:50:13   
TEST: 01              CAGES FROM 0000 TO LAST CAGE             PAGE:   1        
TEST TYPE: CHRONIC          ROUTE: GAVAGE                      NTP C#: 56097    
CONT: N01CP9561903                                             CAS: 57-66-9     
PATHOLOGIST: K. MURTHY                       S. EUSTIS                          
--------------------------------------------------------------------------------
                                                                                
                                                                                
                                                                                


REASONS FOR REMOVAL:                                                            
                                                                                
ALL                                                                             
                                                                                
                                                                                
REMOVAL DATE RANGE:                                                             


ALL                                                                             
                                                                                
TREATMENT GROUPS:                                                               
                                                                                
INCLUDE ALL                                                                     

NTP           STATISTICAL ANALYSIS OF SURVIVAL DATA            REPORT: PEIRPT11
LAB: Mason                                                     DATE: 09/04/94  
EXP: 05030                       PROBENECID                    TIME: 13:50:13  
TEST: 01              CAGES FROM 0000 TO LAST CAGE                             
TEST TYPE: CHRONIC          ROUTE: GAVAGE                      NTP C#: 56097   
CONT: N01CP9561903                                             CAS: 57-66-9    
PATHOLOGIST: K. MURTHY                       S. EUSTIS                         

                                    PROBENECID


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                     MALE RATS
                       FIRST TERMINAL SACRIFICE AT 730 DAYS
                                                          


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = VEHICLE                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 13     CENSORED DEATHS 0    TERMINAL 37        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      293   447   551   597   610   636   653   658   671   707                 |
 |      708   720   727                                                           |
 |  CENSORED DEATHS                                                               |
 |      NONE                                                                      |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = .1G/KG                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 15     CENSORED DEATHS 1    TERMINAL 34        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      292   462   499   503   517   582   616   631   650   664                 |
 |      667   672   694   699   723                                               |
 |  CENSORED DEATHS                                                               |
 |      651                                                                       |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = .4G/KG                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 27     CENSORED DEATHS 1    TERMINAL 22        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      336   372   457   491   499   513   562   574   580   588                 |
 |      600   611   652   660   666   670   690   700   703   704                 |
 |      704   706   707   708   713   723   727                                   |
 |  CENSORED DEATHS                                                               |
 |      695                                                                       |
 |                                                                                |
 ==================================================================================

                                    PROBENECID


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                     MALE RATS
                       FIRST TERMINAL SACRIFICE AT 730 DAYS


 ==================================================================================
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |    DOSE                               TIME (DAYS)                              |
 |                 90   180   270   365   425   485   545   605   665   730 (A)   |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |           |                                                                    |
 |VEHICLE    |   100.0 100.0 100.0  98.0  98.0  96.0  96.0  92.0  84.0  74.0      |
 |           |                                                                    |
 |           |                                                                    |
 |.1G/KG     |   100.0 100.0 100.0  98.0  98.0  96.0  90.0  88.0  80.0  69.7      |
 |           |                                                                    |
 |           |                                                                    |
 |.4G/KG     |   100.0 100.0 100.0  98.0  96.0  94.0  88.0  78.0  72.0  45.4      |
 |           |                                                                    |
 |           |                                                                    |
 ==================================================================================
 ==================================================================================
 |                           SURVIVAL SUMMARY STATISTICS                          |
 |                                                                                |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                                    DOSE                        |
 |                                                                                |
 |                                VEHICLE          .1G/KG           .4G/KG        |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |SURVIVAL AT END OF STUDY|       74.0%            69.7%            45.4%         |
 |(KAPLAN-MEIER)          |                                                       |
 |                        |                                                       |
 |SIGNIFICANCE (B)        |       P=0.003          P=0.722          P=0.006       |
 |(LIFE TABLE)            |                                                       |
 |                        |                                                       |
 |MEAN DAY OF             |       613.7            591.4            615.4         |
 |NATURAL DEATHS (C)      |       (34.3)           (30.1)           (21.1)        |
 |(STANDARD ERROR)        |                                                       |
 |                        |                                                       |
 |MEAN LIFE SPAN (D)      |       699.8            686.8            667.4         |
 |(STANDARD ERROR)        |       (11.3)           (12.7)           (13.9)        |
 |                        |                                                       |
 ==================================================================================
                                    


       (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)

                                    PROBENECID


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                    FEMALE RATS
                       FIRST TERMINAL SACRIFICE AT 729 DAYS
                                                          


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = VEHICLE                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 26     CENSORED DEATHS 0    TERMINAL 24        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      354   495   510   529   544   579   593   620   635   636                 |
 |      636   644   649   651   652   652   663   663   675   677                 |
 |      692   704   720   722   722   722                                         |
 |  CENSORED DEATHS                                                               |
 |      NONE                                                                      |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = .1G/KG                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 15     CENSORED DEATHS 0    TERMINAL 35        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      85    97    537   551   572   592   593   603   617   691                 |
 |      699   708   721   722   722                                               |
 |  CENSORED DEATHS                                                               |
 |      NONE                                                                      |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = .4G/KG                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 50     UNCENSORED DEATHS 30     CENSORED DEATHS 1    TERMINAL 19        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      94    135   203   216   260   266   270   288   495   512                 |
 |      526   557   561   592   592   603   605   624   637   639                 |
 |      649   652   658   670   677   695   698   705   721   722                 |
 |  CENSORED DEATHS                                                               |
 |      604                                                                       |
 |                                                                                |
 ==================================================================================

                                    PROBENECID


                       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)   |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |           |                                                                    |
 |VEHICLE    |   100.0 100.0 100.0  98.0  98.0  98.0  90.0  86.0  64.0  48.0      |
 |           |                                                                    |
 |           |                                                                    |
 |.1G/KG     |    98.0  96.0  96.0  96.0  96.0  96.0  94.0  84.0  82.0  70.0      |
 |           |                                                                    |
 |           |                                                                    |
 |.4G/KG     |   100.0  96.0  86.0  84.0  84.0  84.0  78.0  65.9  53.6  39.2      |
 |           |                                                                    |
 |           |                                                                    |
 ==================================================================================
 ==================================================================================
 |                           SURVIVAL SUMMARY STATISTICS                          |
 |                                                                                |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                                    DOSE                        |
 |                                                                                |
 |                                VEHICLE          .1G/KG           .4G/KG        |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |SURVIVAL AT END OF STUDY|       48.0%            70.0%            39.2%         |
 |(KAPLAN-MEIER)          |                                                       |
 |                        |                                                       |
 |SIGNIFICANCE (B)        |       P=0.041          P=0.048N         P=0.231       |
 |(LIFE TABLE)            |                                                       |
 |                        |                                                       |
 |MEAN DAY OF             |       628.4            567.3            517.4         |
 |NATURAL DEATHS (C)      |       (16.7)           (52.7)           (35.8)        |
 |(STANDARD ERROR)        |                                                       |
 |                        |                                                       |
 |MEAN LIFE SPAN (D)      |       676.7            680.5            599.5         |
 |(STANDARD ERROR)        |       (11.2)           (18.7)           (25.8)        |
 |                        |                                                       |
 ==================================================================================
                                    


       (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)

                                                             PROBENECID
                                                    KAPLAN-MEIER SURVIVAL CURVES
                                                        VEHICLE          = 1
                                                        .1G/KG           = 2
                                                        .4G/KG           = 3

------------------------------------------------------ SPECIES=RATS SEX=MALE -------------------------------------------------------

                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.

            |
            |
        100 +  1                                         1     3
            |                                            1     3     3         1 2
            |                                                        3         1 2    32      1      1
            |                                                                         32 2           1 1
      P  90 +                                                                          3 2         2   1  1
      E     |                                                                            3      3  2   2  1  1
      R     |                                                                                   333    2  2 21 1
      C     |                                                                                     33        2 21    1
      E  80 +                                                                                      3 3        22    11
      N     |                                                                                        3 3             11
      T     |                                                                                          3     332   2  111
            |                                                                                                 33   2   2
      S  70 +                                                                                                          22
      U     |                                                                                                  3  3
      R     |                                                                                                     333
      V     |
      I  60 +
      V     |
      A     |
      L     |                                                                                                       33
         50 +                                                                                                        3 3
            |
            |                                                                                                          33
            |
         40 +
            |
            ---+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+--
               0     6    12    18    24    30    36    42    48    54    60    66    72    78    84    90    96    102   108

                                                                   WEEK

NOTE: 14 obs hidden.

                                                             PROBENECID
                                                    KAPLAN-MEIER SURVIVAL CURVES
                                                        VEHICLE          = 1
                                                        .1G/KG           = 2
                                                        .4G/KG           = 3

----------------------------------------------------- SPECIES=RATS SEX=FEMALE ------------------------------------------------------

                                         Plot of SURVIVAL*WEEK.  Symbol is value of DOSE.

      |
      |
  100 + 1             23                                        1
      |               22      3                                 1                     1
      |                2      3         3 3                                           1 1   12 2
      |                                   3       3                                         1 12  2
   90 +                                                                                       1   21  2
      |                                           33                                               1  1
P     |                                            3  3                               3               1 2 1 1
E     |                                                                               3  3                2          2
R  80 +                                                                                  3  3                        22
C     |                                                                                     3   3           11        2 2
E     |                                                                                         33    3      11         222
N     |                                                                                                       11
T  70 +                                                                                               3 3                 2 2
      |                                                                                                        1 1
S     |                                                                                                 3  33    1 1
U     |                                                                                                     33
R  60 +                                                                                                      33    1 1
V     |                                                                                                       33     1 1
I     |                                                                                                                1 11
V     |                                                                                                        3  33
A  50 +                                                                                                            3  3
L     |                                                                                                                   1 1
      |                                                                                                               33
      |                                                                                                                3 3
   40 +                                                                                                                  33 3
      |
      |
      |
   30 +
      |
      --+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+--
        0         10         20         30         40         50         60         70         80         90         100        110

                                                                   WEEK

NOTE: 17 obs hidden.

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