NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus PULEGONE DATE: 03/31/04 EXPERIMENT: 99020 TEST: 03 TIME: 14:51:53 TEST TYPE: SUBCHRON 90-DAY CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-15460 ROUTE: GAVAGE NTP C#: C99020 PATHOLOGIST: MISSING CAS: 89-82-7 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 RATS REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus PULEGONE DATE: 03/31/04 EXPERIMENT: 99020 TEST: 03 TIME: 14:51:53 TEST TYPE: SUBCHRON 90-DAY CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-15460 ROUTE: GAVAGE NTP C#: C99020 PATHOLOGIST: MISSING CAS: 89-82-7 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF PULEGONE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Heart Mineralization Kidney Accumulation, Hyaline Droplet Kidney: Renal Tubule Casts Protein Regeneration Liver: Bile Duct Hyperplasia Liver: Hepatocyte Hypertrophy Necrosis Focal Liver: Oval Cell Hyperplasia Liver: Periportal Fibrosis Lung Infiltration Cellular Histiocyte Lung: Interstitium Infiltration Cellular Lymphocyte Stomach, Glandular Mineralization Testes: Germinal Epithelium Degeneration =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Heart Cardiomyopathy Kidney Mineralization Kidney: Renal Tubule Casts Protein Liver: Bile Duct Hyperplasia Liver: Hepatocyte Hypertrophy Liver: Oval Cell Hyperplasia Liver: Periportal Fibrosis Lung Infiltration Cellular Histiocyte Lung: Interstitium Infiltration Cellular Lymphocyte Ovary Cyst Stomach, Glandular Mineralization Uterus Dilatation =============================================================== Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/10 (30%) 1/10 (10%) 5/10 (50%) 9/10 (90%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 3/10.00 1/10.00 5/10.00 9/10.00 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 30.0% 10.0% 50.0% 90.0% 100.0% 100.0% | |TERMINAL (d) | 3/10 (30%) 1/10 (10%) 5/10 (50%) 9/10 (90%) 10/10 (100%) 10/10 (100%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.293N P=0.328 P=0.013 * P=0.003 ** P=0.003 ** | |POLY 3 | P<0.001 ** P=0.292N P=0.329 P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.292N P=0.329 P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.292N P=0.329 P=0.003 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.293N P=0.328 P=0.013 * P=0.003 ** P=0.003 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.291N P=0.325 P=0.010 * P=0.002 ** P=0.002 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 10/10 (100%) 9/10 (90%) | |POLY-3 RATE (b) | 1/10.00 1/10.00 1/10.00 1/10.00 10/10.00 9/10.00 | |POLY-3 PERCENT (g) | 10.0% 10.0% 10.0% 10.0% 100.0% 90.0% | |TERMINAL (d) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 10/10 (100%) 8/9 (89%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 9 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.766 P=0.766 P=0.766 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.760 P=0.760 P=0.760 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.760 P=0.760 P=0.760 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.760 P=0.760 P=0.760 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.766 P=0.766 P=0.766 P<0.001 ** (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.763N P=0.763N P=0.763N P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 8/10 (80%) 8/10 (80%) 9/10 (90%) 7/10 (70%) 7/10 (70%) | |POLY-3 RATE (b) | 9/10.00 8/10.00 8/10.00 9/10.00 7/10.00 7/10.00 | |POLY-3 PERCENT (g) | 90.0% 80.0% 80.0% 90.0% 70.0% 70.0% | |TERMINAL (d) | 9/10 (90%) 8/10 (80%) 8/10 (80%) 9/10 (90%) 7/10 (70%) 7/10 (70%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.175N P=0.500N P=0.500N P=0.766 P=0.293N P=0.293N | |POLY 3 | P=0.181N P=0.500N P=0.500N P=0.760 P=0.292N P=0.292N | |POLY 1.5 | P=0.181N P=0.500N P=0.500N P=0.760 P=0.292N P=0.292N | |POLY 6 | P=0.181N P=0.500N P=0.500N P=0.760 P=0.292N P=0.292N | |LOGISTIC REGRESSION| P=0.175N P=0.500N P=0.500N P=0.766 P=0.293N P=0.293N | |COCH-ARM / FISHERS | P=0.173N P=0.500N P=0.500N P=0.763N P=0.291N P=0.291N | |ORDER RESTRICTED | P=0.245N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 3/10 (30%) 0/10 (0%) 4/10 (40%) 5/10 (50%) 2/10 (20%) | |POLY-3 RATE (b) | 6/10.00 3/10.00 0/10.00 4/10.00 5/10.00 2/9.00 | |POLY-3 PERCENT (g) | 60.0% 30.0% 0.0% 40.0% 50.0% 22.2% | |TERMINAL (d) | 6/10 (60%) 3/10 (30%) 0/10 (0%) 4/10 (40%) 5/10 (50%) 2/9 (22%) | |FIRST INCIDENCE | 94 (T) 94 (T) --- 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406N P=0.190N P=0.009N** P=0.331N P=0.500N P=0.121N | |POLY 3 | P=0.411N P=0.186N P<0.001N** P=0.333N P=0.500N P=0.111N | |POLY 1.5 | P=0.408N P=0.186N P<0.001N** P=0.333N P=0.500N P=0.109N | |POLY 6 | P=0.411N P=0.186N P<0.001N** P=0.333N P=0.500N P=0.111N | |LOGISTIC REGRESSION| P=0.406N P=0.190N (e) P=0.331N P=0.500N P=0.121N | |COCH-ARM / FISHERS | P=0.339N P=0.185N P=0.005N** P=0.328N P=0.500N P=0.085N | |ORDER RESTRICTED | P=0.057N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 6/10 (60%) | |POLY-3 RATE (b) | 1/10.00 0/10.00 0/10.00 1/10.00 0/10.00 6/10.00 | |POLY-3 PERCENT (g) | 10.0% 0.0% 0.0% 10.0% 0.0% 60.0% | |TERMINAL (d) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 6/10 (60%) | |FIRST INCIDENCE | 94 (T) --- --- 94 (T) --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500N P=0.500N P=0.766 P=0.500N P=0.034 * | |POLY 3 | P<0.001 ** P=0.500N P=0.500N P=0.760 P=0.500N P=0.018 * | |POLY 1.5 | P<0.001 ** P=0.500N P=0.500N P=0.760 P=0.500N P=0.018 * | |POLY 6 | P<0.001 ** P=0.500N P=0.500N P=0.760 P=0.500N P=0.018 * | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.766 (e) P=0.034 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500N P=0.763N P=0.500N P=0.029 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 1/9.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 11.1% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.095 (e) (e) (e) (e) P=0.479 | |POLY 3 | P=0.098 (e) (e) (e) (e) P=0.479 | |POLY 1.5 | P=0.098 (e) (e) (e) (e) P=0.480 | |POLY 6 | P=0.098 (e) (e) (e) (e) P=0.479 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.479 | |COCH-ARM / FISHERS | P=0.105 (e) (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.050 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/10 (30%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 3/10.00 0/10.00 1/10.00 1/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 30.0% 0.0% 10.0% 10.0% 0.0% 0.0% | |TERMINAL (d) | 3/10 (30%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 94 (T) --- 94 (T) 94 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091N P=0.111N P=0.293N P=0.293N P=0.111N P=0.111N | |POLY 3 | P=0.083N P=0.095N P=0.292N P=0.292N P=0.095N P=0.095N | |POLY 1.5 | P=0.083N P=0.095N P=0.292N P=0.292N P=0.095N P=0.095N | |POLY 6 | P=0.083N P=0.095N P=0.292N P=0.292N P=0.095N P=0.095N | |LOGISTIC REGRESSION| P=0.091N (e) P=0.293N P=0.293N (e) (e) | |COCH-ARM / FISHERS | P=0.089N P=0.105N P=0.291N P=0.291N P=0.105N P=0.105N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION 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 0/9.00 | |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%) 0/9 (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: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 8/10 (80%) 8/10 (80%) 7/10 (70%) 9/10 (90%) 7/10 (70%) | |POLY-3 RATE (b) | 6/10.00 8/10.00 8/10.00 7/10.00 9/10.00 7/10.00 | |POLY-3 PERCENT (g) | 60.0% 80.0% 80.0% 70.0% 90.0% 70.0% | |TERMINAL (d) | 6/10 (60%) 8/10 (80%) 8/10 (80%) 7/10 (70%) 9/10 (90%) 7/10 (70%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.511 P=0.317 P=0.317 P=0.500 P=0.157 P=0.500 | |POLY 3 | P=0.511 P=0.318 P=0.318 P=0.500 P=0.148 P=0.500 | |POLY 1.5 | P=0.511 P=0.318 P=0.318 P=0.500 P=0.148 P=0.500 | |POLY 6 | P=0.511 P=0.318 P=0.318 P=0.500 P=0.148 P=0.500 | |LOGISTIC REGRESSION| P=0.511 P=0.317 P=0.317 P=0.500 P=0.157 P=0.500 | |COCH-ARM / FISHERS | P=0.511 P=0.314 P=0.314 P=0.500 P=0.152 P=0.500 | |ORDER RESTRICTED | P=0.281 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 10/10 (100%) 9/10 (90%) 9/10 (90%) 10/10 (100%) 9/10 (90%) | |POLY-3 RATE (b) | 6/10.00 10/10.00 9/10.00 9/10.00 10/10.00 9/10.00 | |POLY-3 PERCENT (g) | 60.0% 100.0% 90.0% 90.0% 100.0% 90.0% | |TERMINAL (d) | 6/10 (60%) 10/10 (100%) 9/10 (90%) 9/10 (90%) 10/10 (100%) 8/9 (89%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 9 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087 P=0.051 P=0.157 P=0.157 P=0.051 P=0.108 | |POLY 3 | P=0.218 P=0.033 * P=0.148 P=0.148 P=0.033 * P=0.148 | |POLY 1.5 | P=0.218 P=0.033 * P=0.148 P=0.148 P=0.033 * P=0.148 | |POLY 6 | P=0.218 P=0.033 * P=0.148 P=0.148 P=0.033 * P=0.148 | |LOGISTIC REGRESSION| P=0.087 P=0.051 P=0.157 P=0.157 P=0.051 (e) | |COCH-ARM / FISHERS | P=0.228 P=0.043 * P=0.152 P=0.152 P=0.043 * P=0.152 | |ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/10 (70%) 4/10 (40%) 6/10 (60%) 6/10 (60%) 4/10 (40%) 10/10 (100%) | |POLY-3 RATE (b) | 7/10.00 4/10.00 6/10.00 6/10.00 4/10.00 10/10.00 | |POLY-3 PERCENT (g) | 70.0% 40.0% 60.0% 60.0% 40.0% 100.0% | |TERMINAL (d) | 7/10 (70%) 4/10 (40%) 6/10 (60%) 6/10 (60%) 4/10 (40%) 10/10 (100%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039 * P=0.190N P=0.500N P=0.500N P=0.190N P=0.111 | |POLY 3 | P=0.031 * P=0.186N P=0.500N P=0.500N P=0.186N P=0.095 | |POLY 1.5 | P=0.031 * P=0.186N P=0.500N P=0.500N P=0.186N P=0.095 | |POLY 6 | P=0.031 * P=0.186N P=0.500N P=0.500N P=0.186N P=0.095 | |LOGISTIC REGRESSION| P=0.039 * P=0.190N P=0.500N P=0.500N P=0.190N P=0.111 | |COCH-ARM / FISHERS | P=0.037 * P=0.185N P=0.500N P=0.500N P=0.185N P=0.105 | |ORDER RESTRICTED | P=0.018 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 6/10 (60%) | |POLY-3 RATE (b) | 1/10.00 0/10.00 0/10.00 0/10.00 2/10.00 6/9.00 | |POLY-3 PERCENT (g) | 10.0% 0.0% 0.0% 0.0% 20.0% 66.7% | |TERMINAL (d) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 6/9 (67%) | |FIRST INCIDENCE | 94 (T) --- --- --- 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500N P=0.500N P=0.500N P=0.500 P=0.021 * | |POLY 3 | P<0.001 ** P=0.500N P=0.500N P=0.500N P=0.500 P=0.008 ** | |POLY 1.5 | P<0.001 ** P=0.500N P=0.500N P=0.500N P=0.500 P=0.008 ** | |POLY 6 | P<0.001 ** P=0.500N P=0.500N P=0.500N P=0.500 P=0.008 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.500 P=0.021 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500N P=0.500N P=0.500 P=0.029 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Regeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 9/10 (90%) 10/10 (100%) 10/10 (100%) 3/10 (30%) 9/10 (90%) | |POLY-3 RATE (b) | 9/10.00 9/10.00 10/10.00 10/10.00 3/10.00 9/10.00 | |POLY-3 PERCENT (g) | 90.0% 90.0% 100.0% 100.0% 30.0% 90.0% | |TERMINAL (d) | 9/10 (90%) 9/10 (90%) 10/10 (100%) 10/10 (100%) 3/10 (30%) 9/10 (90%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.139N P=0.766 P=0.500 P=0.500 P=0.013N* P=0.766 | |POLY 3 | P=0.086N P=0.760 P=0.500 P=0.500 P=0.003N** P=0.760 | |POLY 1.5 | P=0.086N P=0.760 P=0.500 P=0.500 P=0.003N** P=0.760 | |POLY 6 | P=0.086N P=0.760 P=0.500 P=0.500 P=0.003N** P=0.760 | |LOGISTIC REGRESSION| P=0.139N P=0.766 P=0.500 P=0.500 P=0.013N* P=0.766 | |COCH-ARM / FISHERS | P=0.137N P=0.763N P=0.500 P=0.500 P=0.010N* P=0.763N | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Regeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 1/10.00 0/10.00 0/10.00 0/10.00 0/9.00 | |POLY-3 PERCENT (g) | 0.0% 10.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- 94 (T) --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.501N P=0.500 (e) (e) (e) (e) | |POLY 3 | P=0.471N P=0.500 (e) (e) (e) (e) | |POLY 1.5 | P=0.472N P=0.500 (e) (e) (e) (e) | |POLY 6 | P=0.471N P=0.500 (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.500 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.488N P=0.500 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.374N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 2/10.00 2/10.00 2/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 20.0% 20.0% 20.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- 94 (T) 94 (T) 94 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.156N P=0.234 P=0.234 P=0.234 (e) (e) | |POLY 3 | P=0.153N P=0.227 P=0.227 P=0.227 (e) (e) | |POLY 1.5 | P=0.153N P=0.227 P=0.227 P=0.227 (e) (e) | |POLY 6 | P=0.153N P=0.227 P=0.227 P=0.227 (e) (e) | |LOGISTIC REGRESSION| (e) P=0.234 P=0.234 P=0.234 (e) (e) | |COCH-ARM / FISHERS | P=0.154N P=0.237 P=0.237 P=0.237 (e) (e) | |ORDER RESTRICTED | P=0.228N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 1/10.00 2/10.00 2/10.00 2/10.00 0/10.00 1/9.00 | |POLY-3 PERCENT (g) | 10.0% 20.0% 20.0% 20.0% 0.0% 11.1% | |TERMINAL (d) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 0/10 (0%) 1/9 (11%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.340N P=0.500 P=0.500 P=0.500 P=0.500N P=0.743 | |POLY 3 | P=0.328N P=0.500 P=0.500 P=0.500 P=0.500N P=0.737 | |POLY 1.5 | P=0.328N P=0.500 P=0.500 P=0.500 P=0.500N P=0.738 | |POLY 6 | P=0.328N P=0.500 P=0.500 P=0.500 P=0.500N P=0.737 | |LOGISTIC REGRESSION| P=0.338N P=0.500 P=0.500 P=0.500 (e) P=0.749 | |COCH-ARM / FISHERS | P=0.306N P=0.500 P=0.500 P=0.500 P=0.500N P=0.763N | |ORDER RESTRICTED | P=0.418N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/10 (90%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 9/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 90.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/10 (90%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 1/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 10.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 9/9 (100%) | |FIRST INCIDENCE | --- --- --- --- 94 (T) 9 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.500 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.500 P<0.001N** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.500 P<0.001N** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.500 P<0.001N** | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.500 (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.500 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 100.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001N** (e) (e) (e) P<0.001N** P<0.001 ** | |POLY 1.5 | P<0.001N** (e) (e) (e) P<0.001N** P<0.001 ** | |POLY 6 | P<0.001N** (e) (e) (e) P<0.001N** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/9 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 9 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | P<0.001N** (e) (e) (e) (e) P<0.001N** | |POLY 1.5 | P<0.001N** (e) (e) (e) (e) P<0.001N** | |POLY 6 | P<0.001N** (e) (e) (e) (e) P<0.001N** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 6/10 (60%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 6/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 60.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 6/10 (60%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.009 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.009 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P=0.005 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION 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 0/9.00 | |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%) 0/9 (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: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/10 (90%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 9/9.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/9 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Periportal | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Periportal | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/10 (90%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 9/9.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/9 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 0/10 (0%) 5/10 (50%) 4/10 (40%) 2/10 (20%) 8/10 (80%) | |POLY-3 RATE (b) | 6/10.00 0/10.00 5/10.00 4/10.00 2/10.00 8/10.00 | |POLY-3 PERCENT (g) | 60.0% 0.0% 50.0% 40.0% 20.0% 80.0% | |TERMINAL (d) | 6/10 (60%) 0/10 (0%) 5/10 (50%) 4/10 (40%) 2/10 (20%) 8/10 (80%) | |FIRST INCIDENCE | 94 (T) --- 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.041 * P=0.009N** P=0.500N P=0.331N P=0.091N P=0.317 | |POLY 3 | P=0.025 * P<0.001N** P=0.500N P=0.333N P=0.077N P=0.318 | |POLY 1.5 | P=0.025 * P<0.001N** P=0.500N P=0.333N P=0.077N P=0.318 | |POLY 6 | P=0.025 * P<0.001N** P=0.500N P=0.333N P=0.077N P=0.318 | |LOGISTIC REGRESSION| P=0.041 * (e) P=0.500N P=0.331N P=0.091N P=0.317 | |COCH-ARM / FISHERS | P=0.039 * P=0.005N** P=0.500N P=0.328N P=0.085N P=0.314 | |ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 2/10 (20%) 6/10 (60%) | |POLY-3 RATE (b) | 1/10.00 0/10.00 0/10.00 2/10.00 2/10.00 6/9.00 | |POLY-3 PERCENT (g) | 10.0% 0.0% 0.0% 20.0% 20.0% 66.7% | |TERMINAL (d) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 2/10 (20%) 6/9 (67%) | |FIRST INCIDENCE | 94 (T) --- --- 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500N P=0.500N P=0.500 P=0.500 P=0.021 * | |POLY 3 | P<0.001 ** P=0.500N P=0.500N P=0.500 P=0.500 P=0.008 ** | |POLY 1.5 | P<0.001 ** P=0.500N P=0.500N P=0.500 P=0.500 P=0.008 ** | |POLY 6 | P<0.001 ** P=0.500N P=0.500N P=0.500 P=0.500 P=0.008 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.500 P=0.500 P=0.021 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500N P=0.500 P=0.500 P=0.029 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Interstitium | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/10 (70%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 2/10 (20%) 1/10 (10%) | |POLY-3 RATE (b) | 7/10.00 0/10.00 0/10.00 1/10.00 2/10.00 1/10.00 | |POLY-3 PERCENT (g) | 70.0% 0.0% 0.0% 10.0% 20.0% 10.0% | |TERMINAL (d) | 7/10 (70%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 2/10 (20%) 1/10 (10%) | |FIRST INCIDENCE | 94 (T) --- --- 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155N P=0.003N** P=0.003N** P=0.013N* P=0.040N* P=0.013N* | |POLY 3 | P=0.107N P<0.001N** P<0.001N** P=0.003N** P=0.024N* P=0.003N** | |POLY 1.5 | P=0.107N P<0.001N** P<0.001N** P=0.003N** P=0.024N* P=0.003N** | |POLY 6 | P=0.107N P<0.001N** P<0.001N** P=0.003N** P=0.024N* P=0.003N** | |LOGISTIC REGRESSION| P=0.155N (e) (e) P=0.013N* P=0.040N* P=0.013N* | |COCH-ARM / FISHERS | P=0.153N P=0.002N** P=0.002N** P=0.010N* P=0.035N* P=0.010N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Interstitium | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/10 (40%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/9.00 | |POLY-3 PERCENT (g) | 40.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/10 (40%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | |FIRST INCIDENCE | 94 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.063N P=0.051N P=0.051N P=0.051N P=0.051N P=0.063N | |POLY 3 | P=0.030N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.045N* | |POLY 1.5 | P=0.030N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.045N* | |POLY 6 | P=0.030N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.045N* | |LOGISTIC REGRESSION| P=0.063N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.058N P=0.043N* P=0.043N* P=0.043N* P=0.043N* P=0.043N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 3/10 (30%) 6/10 (60%) | |POLY-3 RATE (b) | 1/10.00 2/10.00 2/10.00 2/10.00 3/10.00 6/9.00 | |POLY-3 PERCENT (g) | 10.0% 20.0% 20.0% 20.0% 30.0% 66.7% | |TERMINAL (d) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) 3/10 (30%) 6/9 (67%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.500 P=0.500 P=0.500 P=0.293 P=0.021 * | |POLY 3 | P=0.003 ** P=0.500 P=0.500 P=0.500 P=0.292 P=0.008 ** | |POLY 1.5 | P=0.003 ** P=0.500 P=0.500 P=0.500 P=0.292 P=0.008 ** | |POLY 6 | P=0.003 ** P=0.500 P=0.500 P=0.500 P=0.292 P=0.008 ** | |LOGISTIC REGRESSION| P=0.003 ** P=0.500 P=0.500 P=0.500 P=0.293 P=0.021 * | |COCH-ARM / FISHERS | P=0.006 ** P=0.500 P=0.500 P=0.500 P=0.291 P=0.029 * | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 0/0.00 0/0.00 2/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 20.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138 (e) (e) (e) (e) P=0.234 | |POLY 3 | (e) (e) (e) (e) (e) P=0.227 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.227 | |POLY 6 | (e) (e) (e) (e) (e) P=0.227 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.234 | |COCH-ARM / FISHERS | P=0.132 (e) (e) (e) (e) P=0.237 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/10 (50%) 3/10 (30%) 5/10 (50%) 2/10 (20%) 3/10 (30%) 9/10 (90%) | |POLY-3 RATE (b) | 5/10.00 3/10.00 5/10.00 2/10.00 3/10.00 9/10.00 | |POLY-3 PERCENT (g) | 50.0% 30.0% 50.0% 20.0% 30.0% 90.0% | |TERMINAL (d) | 5/10 (50%) 3/10 (30%) 5/10 (50%) 2/10 (20%) 3/10 (30%) 9/10 (90%) | |FIRST INCIDENCE | 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016 * P=0.328N P=0.669 P=0.180N P=0.328N P=0.077 | |POLY 3 | P=0.011 * P=0.329N P=0.664 P=0.174N P=0.329N P=0.061 | |POLY 1.5 | P=0.011 * P=0.329N P=0.664 P=0.174N P=0.329N P=0.061 | |POLY 6 | P=0.011 * P=0.329N P=0.664 P=0.174N P=0.329N P=0.061 | |LOGISTIC REGRESSION| P=0.016 * P=0.328N P=0.669 P=0.180N P=0.328N P=0.077 | |COCH-ARM / FISHERS | P=0.016 * P=0.325N P=0.672N P=0.175N P=0.325N P=0.070 | |ORDER RESTRICTED | P=0.007 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 3/10 (30%) 2/10 (20%) 2/10 (20%) 6/10 (60%) 7/10 (70%) | |POLY-3 RATE (b) | 0/10.00 3/10.00 2/10.00 2/10.00 6/10.00 7/9.00 | |POLY-3 PERCENT (g) | 0.0% 30.0% 20.0% 20.0% 60.0% 77.8% | |TERMINAL (d) | 0/10 (0%) 3/10 (30%) 2/10 (20%) 2/10 (20%) 6/10 (60%) 7/9 (78%) | |FIRST INCIDENCE | --- 94 (T) 94 (T) 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.111 P=0.234 P=0.234 P=0.009 ** P=0.002 ** | |POLY 3 | P<0.001 ** P=0.095 P=0.227 P=0.227 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.095 P=0.227 P=0.227 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.095 P=0.227 P=0.227 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) P=0.111 P=0.234 P=0.234 P=0.009 ** P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.105 P=0.237 P=0.237 P=0.005 ** P=0.002 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 2/2 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 2/2.00 0/0.00 0/0.00 0/0.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 100.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 2/2 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- 94 (T) --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.211N P=0.010 * (e) (e) (e) (e) | |POLY 3 | (e) P=0.015 * (e) (e) (e) (e) | |POLY 1.5 | (e) P=0.015 * (e) (e) (e) (e) | |POLY 6 | (e) P=0.015 * (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.010 * (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.206N P=0.015 * (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) | |POLY-3 RATE (b) | 2/10.00 0/0.00 0/0.00 0/10.00 1/10.00 1/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% 10.0% 10.0% | |TERMINAL (d) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) | |FIRST INCIDENCE | 94 (T) --- --- --- 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.500N P=1.000N P=1.000N P=0.234N P=0.500N P=0.500N | |POLY 3 | (e) (e) (e) P=0.227N P=0.500N P=0.500N | |POLY 1.5 | (e) (e) (e) P=0.227N P=0.500N P=0.500N | |POLY 6 | (e) (e) (e) P=0.227N P=0.500N P=0.500N | |LOGISTIC REGRESSION| P=0.500N (e) (e) (e) P=0.500N P=0.500N | |COCH-ARM / FISHERS | P=0.500N P=1.000 P=1.000 P=0.237N P=0.500N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/10.00 0/0.00 0/0.00 0/0.00 0/10.00 0/9.00 | |POLY-3 PERCENT (g) | 10.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/10 (10%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) 0/9 (0%) | |FIRST INCIDENCE | 94 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.282N P=1.000 P=1.000 P=1.000 P=0.500N P=0.521N | |POLY 3 | (e) (e) (e) (e) P=0.500N P=0.521N | |POLY 1.5 | (e) (e) (e) (e) P=0.500N P=0.520N | |POLY 6 | (e) (e) (e) (e) P=0.500N P=0.521N | |LOGISTIC REGRESSION| P=0.282N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.267N P=1.000 P=1.000 P=1.000 P=0.500N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99020 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - PULEGONE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 9.375 18.75 37.5 75 150 | | | MG/KG MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/9.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | |FIRST INCIDENCE | 94 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.213N P=0.234N P=0.234N P=0.234N P=0.234N P=0.257N | |POLY 3 | P=0.183N P=0.227N P=0.227N P=0.227N P=0.227N P=0.252N | |POLY 1.5 | P=0.183N P=0.227N P=0.227N P=0.227N P=0.227N P=0.251N | |POLY 6 | P=0.183N P=0.227N P=0.227N P=0.227N P=0.227N P=0.252N | |LOGISTIC REGRESSION| P=0.213N (e) (e) (e) (e) P=0.251N | |COCH-ARM / FISHERS | P=0.203N P=0.237N P=0.237N P=0.237N P=0.237N P=0.237N | |ORDER RESTRICTED | P=0.009N** (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).