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TDMS Study 05211-06 Pathology Tables


NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 12/02/98       
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:23:55       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408       
PATHOLOGIST: FARNELL, D.                                                                                       CAS: 518-82-1        
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                                                         53 WEEK SSAC MICE                                                          
               REASONS FOR REMOVAL:    25017 Scheduled Sacrifice                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Southern Research Inst                                      EMODIN                                        DATE: 12/02/98     
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:23:55     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408     
PATHOLOGIST: FARNELL, D.                                                                                       CAS: 518-82-1      
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                      EMODIN
===============================================================
Male Mice
------------
Organ                                 Morphology
-----                                 ----------
Kidney: Renal Tubule                   Pigmentation
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
Kidney                                 Nephropathy
Kidney: Renal Tubule                   Pigmentation
Liver                                  Basophilic Focus
===============================================================
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                       EMODIN
                                         Terminal Sacrifice at 143 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%)|4/10 (40%)   4/10 (40%)   5/10 (50%)   9/10 (90%)   |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       100.0%       100.0%      |92.9%        92.9%        95.2%        99.4%        |
|INT SACRIFICE 1 (c)|     10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%)|4/10 (40%)   4/10 (40%)   5/10 (50%)   9/10 (90%)   |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     369 (I)      369 (I)      369 (I)      369 (I)     |370 (I)      370 (I)      370 (I)      370 (I)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.013 *    P=0.672      P=0.500      P=0.034 *    |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.008 **   P=0.574      P=0.410      P=0.010 *    |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.009 **   P=0.592      P=0.427      P=0.011 *    |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.008 **   P=0.569      P=0.405      P=0.009 **   |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.012 *    P=0.675N     P=0.500      P=0.029 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   2/10 (20%)   0/10 (0%)   |0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         68.8%        83.2%        0.0%        |0.0%         68.6%        0.0%         0.0%         |
|INT SACRIFICE 1 (c)|     0/10 (0%)    1/10 (10%)   2/10 (20%)   0/10 (0%)   |0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)    |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          369 (I)      369 (I)      ---         |---          370 (I)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.619N     P=0.500      P=0.234      (e)         |P=0.567N     P=0.500      (e)          (e)          |
|POLY 3             |     P=0.473N     P=0.174      P=0.073      (e)         |P=0.318N     P=0.174      (e)          (e)          |
|POLY 1.5           |     P=0.493N     P=0.227      P=0.097      (e)         |P=0.361N     P=0.228      (e)          (e)          |
|POLY 6             |     P=0.469N     P=0.159      P=0.067      (e)         |P=0.306N     P=0.159      (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.620N     P=0.500      P=0.237      (e)         |P=0.568N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                       EMODIN
                                         Terminal Sacrifice at 143 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/10 (0%)    7/10 (70%)   10/10 (100%) 10/10 (100%)|0/10 (0%)    0/10 (0%)    7/10 (70%)   10/10 (100%) |
|POLY-3 ADJUSTED (b)|     0.0%         97.9%        100.0%       100.0%      |0.0%         0.0%         97.9%        100.0%       |
|INT SACRIFICE 1 (c)|     0/10 (0%)    7/10 (70%)   10/10 (100%) 10/10 (100%)|0/10 (0%)    0/10 (0%)    7/10 (70%)   10/10 (100%) |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          369 (I)      369 (I)      369 (I)     |---          ---          370 (I)      370 (I)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |P<0.001 **   (e)          P=0.003 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P=1.000N     P=1.000N    |P<0.001 **   (e)          P<0.001 **   P=1.000N     |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=1.000N     P=1.000N    |P<0.001 **   (e)          P<0.001 **   P=1.000N     |
|POLY 6             |     P<0.001 **   P<0.001 **   P=1.000N     P=1.000N    |P<0.001 **   (e)          P<0.001 **   P=1.000N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   (e)          P=0.002 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)   |2/10 (20%)   0/10 (0%)    0/10 (0%)    0/10 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |83.1%        0.0%         0.0%         0.0%         |
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)   |2/10 (20%)   0/10 (0%)    0/10 (0%)    0/10 (0%)    |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |370 (I)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.113N     P=0.234N     P=0.234N     P=0.234N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.040N*    P=0.073N     P=0.073N     P=0.073N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.048N*    P=0.097N     P=0.097N     P=0.097N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.038N*    P=0.067N     P=0.067N     P=0.067N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.110N     P=0.237N     P=0.237N     P=0.237N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                       EMODIN
                                         Terminal Sacrifice at 143 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Inflammation Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/10 (40%)   4/10 (40%)   2/10 (20%)   6/10 (60%)  |10/10 (100%) 8/10 (80%)   8/10 (80%)   9/10 (90%)   |
|POLY-3 ADJUSTED (b)|     93.0%        93.0%        83.2%        96.7%       |100.0%       98.7%        98.7%        99.4%        |
|INT SACRIFICE 1 (c)|     4/10 (40%)   4/10 (40%)   2/10 (20%)   6/10 (60%)  |10/10 (100%) 8/10 (80%)   8/10 (80%)   9/10 (90%)   |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     369 (I)      369 (I)      369 (I)      369 (I)     |370 (I)      370 (I)      370 (I)      370 (I)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.258      P=0.672      P=0.317N     P=0.331     |P=0.468N     P=0.234N     P=0.234N     P=0.500N     |
|POLY 3             |     P=0.228      P=0.574      P=0.208N     P=0.257     |P=0.459N     P=0.202N     P=0.202N     P=0.479N     |
|POLY 1.5           |     P=0.235      P=0.592      P=0.228N     P=0.271     |P=0.460N     P=0.207N     P=0.207N     P=0.483N     |
|POLY 6             |     P=0.226      P=0.569      P=0.202N     P=0.253     |P=0.458N     P=0.200N     P=0.200N     P=0.478N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.256      P=0.675N     P=0.314N     P=0.328     |P=0.468N     P=0.237N     P=0.237N     P=0.500N     |
|=================================================================================================================================|
(a)  Number of tumor-bearing animals /  number of animals examined at site.
(b)  Poly-3 adjusted lifetime tumor incidence.
(d)  Observed incidence at terminal kill.
(f)  Beneath the control incidence are the P-values associated with the trend 
test.  Beneath the dosed group incidence are the P-values corresponding to 
pairwise comparisons between the controls and that dosed group.  The life
table analysis regards tumors in animals dying prior to  terminal kill as
 being (directly or indirectly) the cause of death.
Logistic regression is an alternative
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage
and Fishers exact tests compare directly the overall incidence rates
For all tests a negative trend is indicated by N
(e)  Value of Statistic cannot be computed.
(I)  Interim sacrifice
(T)  Terminal sacrifice
#   Tumor rates based on number of animals necropsied.
*   To the right of any statistical result, indicates significance at (P<=0.05).
**  To the right of any statistical result, indicates significance at (P<=0.01).