National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/1652

TDMS Study 05150-02 Pathology Tables

NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11     
LAB: Mason                                            METHYLPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 02                                                                                     TIME: 10:17:04       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65132                              ROUTE: DOSED FEED                                              NTP C#: 56280B       
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  

NTP                                         STATISTICAL ANALYSIS OF SURVIVAL DATA                              REPORT: PEIRPT11    
LAB: Mason                                            METHYLPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95      
EXPERIMENT: 05150 TEST: 02                                                                                     TIME: 10:17:04      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-65132                              ROUTE: DOSED FEED                                              NTP C#: 56280B      
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9       

                           METHYLPHENIDATE HYDROCHLORIDE


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


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = 0 PPM                                    |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 5      CENSORED DEATHS 20   TERMINAL 45        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      537   617   639   640   679                                               |
 |  CENSORED DEATHS                                                               |
 |      274   274   274   274   275   275   275   275   275   275                 |
 |      454   454   454   454   454   454   455   455   455   455                 |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = 50 PPM                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 5      CENSORED DEATHS 20   TERMINAL 45        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      628   674   707   708   720                                               |
 |  CENSORED DEATHS                                                               |
 |      274   274   274   274   274   274   274   274   275   275                 |
 |      454   454   454   455   455   455   455   455   455   455                 |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = 250 PPM                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 6      CENSORED DEATHS 20   TERMINAL 44        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      541   585   601   610   626   710                                         |
 |  CENSORED DEATHS                                                               |
 |      274   274   274   274   274   274   275   275   275   275                 |
 |      454   454   454   454   454   454   455   455   455   455                 |
 |                                                                                |
 ==================================================================================

                           METHYLPHENIDATE HYDROCHLORIDE


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


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = 500 PPM                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 9      CENSORED DEATHS 20   TERMINAL 41        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      574   618   626   647   654   684   687   700   707                       |
 |  CENSORED DEATHS                                                               |
 |      274   274   275   275   275   275   275   275   275   275                 |
 |      454   454   454   454   454   455   455   455   455   455                 |
 |                                                                                |
 ==================================================================================

                           METHYLPHENIDATE HYDROCHLORIDE


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                     MALE MICE
                       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)   |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |           |                                                                    |
 |0 PPM      |   100.0 100.0 100.0 100.0 100.0 100.0  98.0  98.0  92.0  90.0      |
 |           |                                                                    |
 |           |                                                                    |
 |50 PPM     |   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0  98.0  90.0      |
 |           |                                                                    |
 |           |                                                                    |
 |250 PPM    |   100.0 100.0 100.0 100.0 100.0 100.0  98.0  94.0  90.0  88.0      |
 |           |                                                                    |
 |           |                                                                    |
 |500 PPM    |   100.0 100.0 100.0 100.0 100.0 100.0 100.0  98.0  90.0  82.0      |
 |           |                                                                    |
 |           |                                                                    |
 ==================================================================================
 ==================================================================================
 |                           SURVIVAL SUMMARY STATISTICS                          |
 |                                                                                |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                                  DOSE                          |
 |                                                                                |
 |                                0 PPM        50 PPM       250 PPM      500 PPM  |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |SURVIVAL AT END OF STUDY|       90.0%        90.0%        88.0%        82.0%    |
 |(KAPLAN-MEIER)          |                                                       |
 |                        |                                                       |
 |SIGNIFICANCE (B)        |       P=0.219      P=1.000N     P=0.967      P=0.414  |
 |(LIFE TABLE)            |                                                       |
 |                        |                                                       |
 |MEAN DAY OF             |       622.4        687.4        612.2        655.2    |
 |NATURAL DEATHS (C)      |       (23.6)       (16.7)       (22.9)       (14.6)   |
 |(STANDARD ERROR)        |                                                       |
 |                        |                                                       |
 |MEAN LIFE SPAN (D)      |       617.9        622.5        615.4        616.0    |
 |(STANDARD ERROR)        |       (20.5)       (20.6)       (20.4)       (20.3)   |
 |                        |                                                       |
 ==================================================================================
                                    


       (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)

                           METHYLPHENIDATE HYDROCHLORIDE


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                    FEMALE MICE
                       FIRST TERMINAL SACRIFICE AT 739 DAYS
                                                          


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = 0 PPM                                    |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 69     UNCENSORED DEATHS 11     CENSORED DEATHS 21   TERMINAL 37        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      67    571   581   621   628   673   684   685   708   708                 |
 |      708                                                                       |
 |  CENSORED DEATHS                                                               |
 |      280   280   280   280   280   280   281   281   281   281                 |
 |      348   455   455   455   455   455   456   456   456   456                 |
 |      456                                                                       |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = 50 PPM                                   |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 69     UNCENSORED DEATHS 14     CENSORED DEATHS 20   TERMINAL 35        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      103   145   158   391   462   588   603   625   628   681                 |
 |      690   690   699   730                                                     |
 |  CENSORED DEATHS                                                               |
 |      12    280   280   280   281   281   281   281   281   281                 |
 |      455   455   455   455   455   456   456   456   456   456                 |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                DOSE = 250 PPM                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 13     CENSORED DEATHS 20   TERMINAL 37        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      57    183   469   578   607   656   686   689   697   705                 |
 |      708   719   728                                                           |
 |  CENSORED DEATHS                                                               |
 |      280   280   280   280   280   281   281   281   281   281                 |
 |      455   455   455   455   455   455   456   456   456   456                 |
 |                                                                                |
 ==================================================================================

                           METHYLPHENIDATE HYDROCHLORIDE


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                    FEMALE MICE
                       FIRST TERMINAL SACRIFICE AT 739 DAYS
                                                          


                          INDIVIDUAL SURVIVAL TIMES (DAYS)
 ==================================================================================
 |                                DOSE = 500 PPM                                  |
 |                             ---------------------                              |
 |                                                                                |
 |  TOTAL 70     UNCENSORED DEATHS 6      CENSORED DEATHS 20   TERMINAL 44        |
 |                                                                                |
 |  UNCENSORED DEATHS                                                             |
 |      648   660   660   677   690   695                                         |
 |  CENSORED DEATHS                                                               |
 |      280   280   280   280   280   280   281   281   281   281                 |
 |      455   455   455   455   456   456   456   456   456   456                 |
 |                                                                                |
 ==================================================================================

                           METHYLPHENIDATE HYDROCHLORIDE


                       STATISTICAL ANALYSIS OF SURVIVAL DATA
                                    FEMALE MICE
                       FIRST TERMINAL SACRIFICE AT 739 DAYS


 ==================================================================================
 |               KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%)                  |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |    DOSE                               TIME (DAYS)                              |
 |                 90   180   270   365   425   485   545   605   665   739 (A)   |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |           |                                                                    |
 |0 PPM      |    98.6  98.6  98.6  98.6  98.6  98.6  98.6  94.4  90.2  77.6      |
 |           |                                                                    |
 |           |                                                                    |
 |50 PPM     |   100.0  95.6  95.6  95.6  93.9  91.8  91.8  87.6  83.5  73.0      |
 |           |                                                                    |
 |           |                                                                    |
 |250 PPM    |    98.6  98.6  97.1  97.1  97.1  95.1  95.1  93.1  89.0  74.9      |
 |           |                                                                    |
 |           |                                                                    |
 |500 PPM    |   100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0  94.0  88.0      |
 |           |                                                                    |
 |           |                                                                    |
 ==================================================================================
 ==================================================================================
 |                           SURVIVAL SUMMARY STATISTICS                          |
 |                                                                                |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |                                                  DOSE                          |
 |                                                                                |
 |                                0 PPM        50 PPM       250 PPM      500 PPM  |
 |                                                                                |
 |--------------------------------------------------------------------------------|
 |SURVIVAL AT END OF STUDY|       77.6%        73.0%        74.9%        88.0%    |
 |(KAPLAN-MEIER)          |                                                       |
 |                        |                                                       |
 |SIGNIFICANCE (B)        |       P=0.102N     P=0.597      P=0.888      P=0.235N |
 |(LIFE TABLE)            |                                                       |
 |                        |                                                       |
 |MEAN DAY OF             |       603.1        513.8        575.5        671.7    |
 |NATURAL DEATHS (C)      |       (55.7)       (60.2)       (59.9)       ( 7.6)   |
 |(STANDARD ERROR)        |                                                       |
 |                        |                                                       |
 |MEAN LIFE SPAN (D)      |       604.1        581.9        602.6        627.2    |
 |(STANDARD ERROR)        |       (22.4)       (24.8)       (22.8)       (20.7)   |
 |                        |                                                       |
 ==================================================================================
                                    


       (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)

                                                   METHYLPHENIDATE HYDROCHLORIDE
                                                    KAPLAN-MEIER SURVIVAL CURVES
                                                        0 PPM            = 1
                                                        50 PPM           = 2
                                                        250 PPM          = 3
                                                        500 PPM          = 4

------------------------------------------------------ SPECIES=MICE SEX=MALE -------------------------------------------------------

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

      |
      |
  100 + 1                                                                                    13   4        2
      |
      |
      |
   98 +                                                                                      13   4 3     12       2
      |
      |
      |
   96 +                                                                                             3  3  14 1     2   2
      |
P     |
E     |
R  94 +                                                                                                3 3 4  4        22
C     |
E     |
N     |
T  92 +                                                                                                  3 3 144   1    22
      |
S     |
U     |
R  90 +                                                                                                    3   4   14   32  1
V     |
I     |
V     |
A  88 +                                                                                                             44  3   3
L     |
      |
      |
   86 +                                                                                                              44
      |
      |
      |
   84 +                                                                                                               44
      |
      |
      |
   82 +                                                                                                                4    4
      |
      --+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+--
        0         10         20         30         40         50         60         70         80         90         100        110

                                                                   WEEK

NOTE: 6 obs hidden.

                                                   METHYLPHENIDATE HYDROCHLORIDE
                                                    KAPLAN-MEIER SURVIVAL CURVES
                                                        0 PPM            = 1
                                                        50 PPM           = 2
                                                        250 PPM          = 3
                                                        500 PPM          = 4

----------------------------------------------------- SPECIES=MICE SEX=FEMALE ------------------------------------------------------

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

      |
      |
  100 + 1         31     2                                                                                    4
      |           31     2     2      3                                                           1
      |                        2 2    3                                           3                           4  4
      |                                                                                           11
P  95 +                          2                                    2           3                3
E     |                                                               2          2                 1      1      4 4
R     |                                                                                            3    3 11       4 4
C     |                                                                          2                  2   3      3
E  90 +                                                                                             2   2  1       1 44
N     |                                                                                                        3    3
T     |                                                                                                 2  2       1134      4
      |
S  85 +                                                                                                              33
U     |                                                                                                    2        1   1
R     |                                                                                                               33
V     |                                                                                                             22 33
I  80 +
V     |                                                                                                                 33
A     |                                                                                                              22 133  1
L     |
   75 +                                                                                                               2   3 23
      |
      |                                                                                                                     22
      |
   70 +
      |
      --+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+----------+--
        0         10         20         30         40         50         60         70         80         90         100        110

                                                                   WEEK

NOTE: 5 obs hidden.
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.