National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/40985

P08 - Statistical Analysis of Primary Tumors (Rats)

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     

LAB: Battelle Columbus                                         ESTRAGOLE                                       DATE: 10/08/03       

EXPERIMENT: 60946 TEST: 01                                                                                     TIME: 09:15:14       

TEST TYPE:  SUBCHRON 90-DAY                     CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        

CONT: NO1-ES-15460                              ROUTE: GAVAGE                                                  NTP C#: C60946       

PATHOLOGIST: MISSING                                                                                           CAS: 140-67-0        

------------------------------------------------------------------------------------------------------------------------------------

                                                                                                                                    

                                                             FINAL/RATS                                                             

                                                                                                                                    

                                                                                                                                    

               REASONS FOR REMOVAL:    ALL                                                                                          

                                                                                                                                    

                                                                                                                                    

                                                                                                                                    

                                                                                                                                    

                                                                                                                                    

               REMOVAL DATE RANGE:     ALL                                                                                          

                                                                                                                                    

               TREATMENT GROUPS:       INCLUDE ALL                                                                                  

                                                                                                                                   

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     

LAB: Battelle Columbus                                         ESTRAGOLE                                       DATE: 10/08/03       

EXPERIMENT: 60946 TEST: 01                                                                                     TIME: 09:15:14       

TEST TYPE:  SUBCHRON 90-DAY                     CAGES FROM 0000 TO LAST CAGE                                                        

CONT: NO1-ES-15460                              ROUTE: GAVAGE                                                  NTP C#: C60946       

PATHOLOGIST: MISSING                                                                                           CAS: 140-67-0        

Rats(FISCHER 344)                                                                                                                   

-----------------------------                                                                                                       

FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   

BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 

ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      

                                                 ---------------                                                                    

                                                 Liver                                                                              

                                                 Lung                                                                               

                                                                                                                                   

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     

LAB: Battelle Columbus                                         ESTRAGOLE                                       DATE: 10/08/03       

EXPERIMENT: 60946 TEST: 01                                                                                     TIME: 09:15:14       

TEST TYPE:  SUBCHRON 90-DAY                     CAGES FROM 0000 TO LAST CAGE                                                        

CONT: NO1-ES-15460                              ROUTE: GAVAGE                                                  NTP C#: C60946       

PATHOLOGIST: MISSING                                                                                           CAS: 140-67-0        

                                                                                                                                    

                                                                                                                                    

SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               

IN THE ANALYSIS OF                       ESTRAGOLE                                                                                  

===============================================================                                                                     

Male Rats                                                                                                                           

------------                                                                                                                        

Organ                                 Morphology                                                                                    

-----                                 ----------                                                                                    

Liver                                  Cholangiocarcinoma                                                                           

All Organs                             Malignant Tumors                                                                             

                                       Malignant and Benign Tumors                                                                  

===============================================================                                                                     

                                                                                                                                   

       Date:  10/08/03                           EXPERIMENT: 60946 TEST: 01                                            Page 1       

                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)        -                        ESTRAGOLE          

                                         Terminal Sacrifice at 14 weeks                                                             

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Males                                                  | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|Liver                                                                                                                            | 

|     Cholangiocarcinoma                                                                                                          | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |                                                                                                             | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 

|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          2/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             20.0%           | 

|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 

|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              93 (T)          | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        P=0.011 *        (e)              (e)              (e)              (e)              P=0.234         | 

|POLY 3             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|POLY 1.5           |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|POLY 6             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.234         | 

|COCH-ARM / FISHERS |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.237         | 

|ORDER RESTRICTED   |        P=0.007 **       (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Females                                                | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|Liver                                                                                                                            | 

|     Cholangiocarcinoma                                                                                                          | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |                                                                                                             | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 

|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 

|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

                                                                                                                                   

       Date:  10/08/03                           EXPERIMENT: 60946 TEST: 01                                            Page 2       

                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                        ESTRAGOLE           

                                         Terminal Sacrifice at 14 weeks                                                             

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Males                                                  | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|All Organs                                                                                                                       | 

|     Malignant Tumors                                                                                                            | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |        #                #                #                #                #                #               | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 

|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          2/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             20.0%           | 

|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 

|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              93 (T)          | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        P=0.011 *        (e)              (e)              (e)              (e)              P=0.234         | 

|POLY 3             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|POLY 1.5           |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|POLY 6             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.227         | 

|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.234         | 

|COCH-ARM / FISHERS |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.237         | 

|ORDER RESTRICTED   |        P=0.007 **       (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Females                                                | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|All Organs                                                                                                                       | 

|     Malignant Tumors                                                                                                            | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |        #                #                #                #                #                #               | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 

|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 

|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

                                                                                                                                   

       Date:  10/08/03                           EXPERIMENT: 60946 TEST: 01                                            Page 3       

                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                        ESTRAGOLE           

                                         Terminal Sacrifice at 14 weeks                                                             

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Males                                                  | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|All Organs                                                                                                                       | 

|     Malignant and Benign Tumors                                                                                                 | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |        #                #                #                #                #                #               | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        3/10 (30%)      | 

|POLY-3 RATE (b)    |        0/10.00          1/10.00          0/10.00          0/10.00          0/10.00          3/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             10.0%            0.0%             0.0%             0.0%             30.0%           | 

|TERMINAL (d)       |        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        3/10 (30%)      | 

|FIRST INCIDENCE    |        ---              93 (T)           ---              ---              ---              93 (T)          | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        P=0.011 *        P=0.500          (e)              (e)              (e)              P=0.111         | 

|POLY 3             |        P=0.008 **       P=0.500          (e)              (e)              (e)              P=0.095         | 

|POLY 1.5           |        P=0.008 **       P=0.500          (e)              (e)              (e)              P=0.095         | 

|POLY 6             |        P=0.008 **       P=0.500          (e)              (e)              (e)              P=0.095         | 

|LOGISTIC REGRESSION|        (e)              P=0.500          (e)              (e)              (e)              P=0.111         | 

|COCH-ARM / FISHERS |        P=0.011 *        P=0.500          (e)              (e)              (e)              P=0.105         | 

|ORDER RESTRICTED   |        P=0.003 **       (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

|                   |                                                                                                             | 

|                   |                                                      Females                                                | 

|Dose               |        0 MG/KG          37.5             75               150              300              600             | 

|                   |                         MG/KG            MG/KG            MG/KG            MG/KG            MG/KG           | 

|=================================================================================================================================| 

|                                                                                                                                 | 

|All Organs                                                                                                                       | 

|     Malignant and Benign Tumors                                                                                                 | 

|                                                                                                                                 | 

|                                                                                                                                 | 

|---------------------------------------------------------------------------------------------------------------------------------| 

|TUMOR RATES        |        #                #                #                #                #                #               | 

|-----------        |                                                                                                             | 

|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 

|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 

|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 

|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 

|-------------------|                                                                                                             | 

|STATISTICAL TESTS  |                                                                                                             | 

|-------------------|                                                                                                             | 

|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 

|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 

|=================================================================================================================================| 

(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         

(b)  Number of tumor-bearing animals / Poly-3 number                                                                                

(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.                                                                                         

(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      

(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).                                                    


NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.