TDMS Study 56348-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus CITRAL DATE: 12/19/00 EXPERIMENT: 56348 TEST: 04 TIME: 14:34:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: DR. M. RYAN CAS: 5392-40-5 Mice(B6C3F1) ----------------------------- 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. --------------- Adrenal Cortex Adrenal Medulla Bone Marrow Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Liver Lung Ovary Pancreas Pituitary Gland Spleen Testes Thymus Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus CITRAL DATE: 12/19/00 EXPERIMENT: 56348 TEST: 04 TIME: 14:34:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: DR. M. RYAN CAS: 5392-40-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF CITRAL =============================================================== Male Mice ------------ Organ Morphology ----- ---------- All Organs Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type =============================================================== Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) | 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 2/48.80 2/46.15 | 1/43.96 2/46.22 | |POLY-3 PERCENT (g) | 4.1% 4.3% | 2.3% 4.3% | |TERMINAL (d) | 2/48 (4%) 2/43 (5%) | 1/40 (3%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.654 | P=0.509 | |POLY 3 | P=0.679 | P=0.512 | |POLY 1.5 | P=0.682 | P=0.511 | |POLY 6 | P=0.675 | P=0.512 | |LOGISTIC REGRESSION| P=0.654 | P=0.509 | |COCH-ARM / FISHERS | P=0.691N | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) | 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 2/48.80 2/46.15 | 2/43.96 2/46.22 | |POLY-3 PERCENT (g) | 4.1% 4.3% | 4.6% 4.3% | |TERMINAL (d) | 2/48 (4%) 2/43 (5%) | 2/40 (5%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.654 | P=0.686N | |POLY 3 | P=0.679 | P=0.671N | |POLY 1.5 | P=0.682 | P=0.674N | |POLY 6 | P=0.675 | P=0.672N | |LOGISTIC REGRESSION| P=0.654 | P=0.686N | |COCH-ARM / FISHERS | P=0.691N | P=0.691N | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Intestine Small: Jejunum | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.80 2/46.15 | 0/43.96 0/46.22 | |POLY-3 PERCENT (g) | 2.1% 4.3% | 0.0% 0.0% | |TERMINAL (d) | 1/48 (2%) 2/43 (5%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.462 | (e) | |POLY 3 | P=0.487 | (e) | |POLY 1.5 | P=0.491 | (e) | |POLY 6 | P=0.484 | (e) | |LOGISTIC REGRESSION| P=0.462 | (e) | |COCH-ARM / FISHERS | P=0.500 | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Intestine Small: Site Unspecified | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.80 2/46.15 | 0/43.96 0/46.22 | |POLY-3 PERCENT (g) | 2.1% 4.3% | 0.0% 0.0% | |TERMINAL (d) | 1/48 (2%) 2/43 (5%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.462 | (e) | |POLY 3 | P=0.487 | (e) | |POLY 1.5 | P=0.491 | (e) | |POLY 6 | P=0.484 | (e) | |LOGISTIC REGRESSION| P=0.462 | (e) | |COCH-ARM / FISHERS | P=0.500 | (e) | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Intestine Small: Site Unspecified | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) | 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 3/46.15 | 0/43.96 0/46.22 | |POLY-3 PERCENT (g) | 4.1% 6.5% | 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 3/43 (7%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.450 | (e) | |POLY 3 | P=0.480 | (e) | |POLY 1.5 | P=0.485 | (e) | |POLY 6 | P=0.474 | (e) | |LOGISTIC REGRESSION| P=0.450 | (e) | |COCH-ARM / FISHERS | P=0.500 | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) | 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/48.80 0/46.15 | 0/43.96 0/46.22 | |POLY-3 PERCENT (g) | 4.1% 0.0% | 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 0/43 (0%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) --- | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.263N | (e) | |POLY 3 | P=0.257N | (e) | |POLY 1.5 | P=0.252N | (e) | |POLY 6 | P=0.263N | (e) | |LOGISTIC REGRESSION| (e) | (e) | |COCH-ARM / FISHERS | P=0.247N | (e) | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 10/50 (20%) | 5/50 (10%) 3/49 (6%) | |POLY-3 RATE (b) | 10/48.80 10/46.76 | 5/43.96 3/46.22 | |POLY-3 PERCENT (g) | 20.5% 21.4% | 11.4% 6.5% | |TERMINAL (d) | 10/48 (21%) 9/43 (21%) | 5/40 (13%) 3/41 (7%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.495 | P=0.342N | |POLY 3 | P=0.559 | P=0.326N | |POLY 1.5 | P=0.567 | P=0.331N | |POLY 6 | P=0.549 | P=0.327N | |LOGISTIC REGRESSION| P=0.564 | P=0.342N | |COCH-ARM / FISHERS | P=0.598N | P=0.369N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 9/50 (18%) | 1/50 (2%) 3/49 (6%) | |POLY-3 RATE (b) | 4/48.80 9/46.76 | 1/43.96 3/46.52 | |POLY-3 PERCENT (g) | 8.2% 19.3% | 2.3% 6.5% | |TERMINAL (d) | 4/48 (8%) 8/43 (19%) | 1/40 (3%) 1/41 (2%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 680 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.084 | P=0.321 | |POLY 3 | P=0.101 | P=0.321 | |POLY 1.5 | P=0.105 | P=0.318 | |POLY 6 | P=0.098 | P=0.322 | |LOGISTIC REGRESSION| P=0.109 | P=0.314 | |COCH-ARM / FISHERS | P=0.117 | P=0.301 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 15/50 (30%) | 6/50 (12%) 6/49 (12%) | |POLY-3 RATE (b) | 13/48.80 15/46.76 | 6/43.96 6/46.52 | |POLY-3 PERCENT (g) | 26.6% 32.1% | 13.7% 12.9% | |TERMINAL (d) | 13/48 (27%) 14/43 (33%) | 6/40 (15%) 4/41 (10%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 680 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.289 | P=0.599N | |POLY 3 | P=0.362 | P=0.577N | |POLY 1.5 | P=0.373 | P=0.585N | |POLY 6 | P=0.350 | P=0.574N | |LOGISTIC REGRESSION| P=0.355 | P=0.587N | |COCH-ARM / FISHERS | P=0.412 | P=0.606 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 15/50 (30%) | 6/50 (12%) 6/49 (12%) | |POLY-3 RATE (b) | 13/48.80 15/46.76 | 6/43.96 6/46.52 | |POLY-3 PERCENT (g) | 26.6% 32.1% | 13.7% 12.9% | |TERMINAL (d) | 13/48 (27%) 14/43 (33%) | 6/40 (15%) 4/41 (10%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 680 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.289 | P=0.599N | |POLY 3 | P=0.362 | P=0.577N | |POLY 1.5 | P=0.373 | P=0.585N | |POLY 6 | P=0.350 | P=0.574N | |LOGISTIC REGRESSION| P=0.355 | P=0.587N | |COCH-ARM / FISHERS | P=0.412 | P=0.606 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 8/50 (16%) | 3/50 (6%) 2/49 (4%) | |POLY-3 RATE (b) | 4/48.80 8/46.76 | 3/43.96 2/46.22 | |POLY-3 PERCENT (g) | 8.2% 17.1% | 6.8% 4.3% | |TERMINAL (d) | 4/48 (8%) 7/43 (16%) | 3/40 (8%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.135 | P=0.489N | |POLY 3 | P=0.159 | P=0.473N | |POLY 1.5 | P=0.163 | P=0.477N | |POLY 6 | P=0.155 | P=0.474N | |LOGISTIC REGRESSION| P=0.170 | P=0.489N | |COCH-ARM / FISHERS | P=0.178 | P=0.510N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) | 3/50 (6%) 3/49 (6%) | |POLY-3 RATE (b) | 4/48.80 5/46.76 | 3/43.96 3/46.22 | |POLY-3 PERCENT (g) | 8.2% 10.7% | 6.8% 6.5% | |TERMINAL (d) | 4/48 (8%) 4/43 (9%) | 3/40 (8%) 3/41 (7%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.438 | P=0.652N | |POLY 3 | P=0.476 | P=0.635N | |POLY 1.5 | P=0.482 | P=0.639N | |POLY 6 | P=0.471 | P=0.636N | |LOGISTIC REGRESSION| P=0.503 | P=0.652N | |COCH-ARM / FISHERS | P=0.500 | P=0.651 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 12/50 (24%) | 6/50 (12%) 5/49 (10%) | |POLY-3 RATE (b) | 8/48.80 12/46.76 | 6/43.96 5/46.22 | |POLY-3 PERCENT (g) | 16.4% 25.7% | 13.7% 10.8% | |TERMINAL (d) | 8/48 (17%) 11/43 (26%) | 6/40 (15%) 5/41 (12%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.157 | P=0.483N | |POLY 3 | P=0.196 | P=0.462N | |POLY 1.5 | P=0.203 | P=0.467N | |POLY 6 | P=0.189 | P=0.463N | |LOGISTIC REGRESSION| P=0.199 | P=0.483N | |COCH-ARM / FISHERS | P=0.227 | P=0.514N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | | 1/50 (2%) 2/49 (4%) | |POLY-3 RATE (b) | | 1/43.96 2/46.22 | |POLY-3 PERCENT (g) | | 2.3% 4.3% | |TERMINAL (d) | | 1/40 (3%) 2/41 (5%) | |FIRST INCIDENCE | | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | | P=0.509 | |POLY 3 | | P=0.512 | |POLY 1.5 | | P=0.510 | |POLY 6 | | P=0.512 | |LOGISTIC REGRESSION| | P=0.509 | |COCH-ARM / FISHERS | | P=0.492 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/48 (0%) | 4/49 (8%) 4/48 (8%) | |POLY-3 RATE (b) | 0/48.80 0/44.15 | 4/42.96 4/45.22 | |POLY-3 PERCENT (g) | 0.0% 0.0% | 9.3% 8.9% | |TERMINAL (d) | 0/48 (0%) 0/41 (0%) | 4/39 (10%) 4/40 (10%) | |FIRST INCIDENCE | --- --- | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) | P=0.630N | |POLY 3 | (e) | P=0.611N | |POLY 1.5 | (e) | P=0.616N | |POLY 6 | (e) | P=0.612N | |LOGISTIC REGRESSION| (e) | P=0.630N | |COCH-ARM / FISHERS | (e) | P=0.631 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) | 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 1/46.15 | 0/43.96 2/46.78 | |POLY-3 PERCENT (g) | 0.0% 2.2% | 0.0% 4.3% | |TERMINAL (d) | 0/48 (0%) 1/43 (2%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | --- 727 (T) | --- 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478 | P=0.255 | |POLY 3 | P=0.501 | P=0.245 | |POLY 1.5 | P=0.500 | P=0.243 | |POLY 6 | P=0.501 | P=0.246 | |LOGISTIC REGRESSION| P=0.478 | P=0.224 | |COCH-ARM / FISHERS | P=0.500 | P=0.247 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) | 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 1/46.15 | 0/43.96 2/46.78 | |POLY-3 PERCENT (g) | 0.0% 2.2% | 0.0% 4.3% | |TERMINAL (d) | 0/48 (0%) 1/43 (2%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | --- 727 (T) | --- 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478 | P=0.255 | |POLY 3 | P=0.501 | P=0.245 | |POLY 1.5 | P=0.500 | P=0.243 | |POLY 6 | P=0.501 | P=0.246 | |LOGISTIC REGRESSION| P=0.478 | P=0.224 | |COCH-ARM / FISHERS | P=0.500 | P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) | 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 0/46.15 | 0/43.96 2/46.78 | |POLY-3 PERCENT (g) | 0.0% 0.0% | 0.0% 4.3% | |TERMINAL (d) | 0/48 (0%) 0/43 (0%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | --- --- | --- 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) | P=0.255 | |POLY 3 | (e) | P=0.245 | |POLY 1.5 | (e) | P=0.243 | |POLY 6 | (e) | P=0.246 | |LOGISTIC REGRESSION| (e) | P=0.224 | |COCH-ARM / FISHERS | (e) | P=0.247 | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | | 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | | 0/43.96 2/46.22 | |POLY-3 PERCENT (g) | | 0.0% 4.3% | |TERMINAL (d) | | 0/40 (0%) 2/41 (5%) | |FIRST INCIDENCE | | --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | | P=0.244 | |POLY 3 | | P=0.243 | |POLY 1.5 | | P=0.243 | |POLY 6 | | P=0.243 | |LOGISTIC REGRESSION| | P=0.244 | |COCH-ARM / FISHERS | | P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) | 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 0/46.15 | 1/43.96 0/46.22 | |POLY-3 PERCENT (g) | 4.1% 0.0% | 2.3% 0.0% | |TERMINAL (d) | 2/48 (4%) 0/43 (0%) | 1/40 (3%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) --- | 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.263N | P=0.495N | |POLY 3 | P=0.257N | P=0.480N | |POLY 1.5 | P=0.252N | P=0.483N | |POLY 6 | P=0.263N | P=0.481N | |LOGISTIC REGRESSION| (e) | (e) | |COCH-ARM / FISHERS | P=0.247N | P=0.500N | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) | 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 1/46.15 | 0/43.96 0/46.22 | |POLY-3 PERCENT (g) | 4.1% 2.2% | 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 1/43 (2%) | 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.538N | (e) | |POLY 3 | P=0.526N | (e) | |POLY 1.5 | P=0.519N | (e) | |POLY 6 | P=0.534N | (e) | |LOGISTIC REGRESSION| P=0.538N | (e) | |COCH-ARM / FISHERS | P=0.500N | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) | 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 4/48.80 1/46.15 | 1/43.96 0/46.22 | |POLY-3 PERCENT (g) | 8.2% 2.2% | 2.3% 0.0% | |TERMINAL (d) | 4/48 (8%) 1/43 (2%) | 1/40 (3%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) | 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215N | P=0.495N | |POLY 3 | P=0.200N | P=0.480N | |POLY 1.5 | P=0.195N | P=0.483N | |POLY 6 | P=0.207N | P=0.481N | |LOGISTIC REGRESSION| P=0.215N | (e) | |COCH-ARM / FISHERS | P=0.181N | P=0.500N | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) | 4/50 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 4/50.00 0/46.15 | 4/43.96 3/46.28 | |POLY-3 PERCENT (g) | 8.0% 0.0% | 9.1% 6.5% | |TERMINAL (d) | 2/48 (4%) 0/43 (0%) | 4/40 (10%) 2/41 (5%) | |FIRST INCIDENCE | 397 --- | 733 (T) 719 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.077N | P=0.487N | |POLY 3 | P=0.075N | P=0.468N | |POLY 1.5 | P=0.071N | P=0.472N | |POLY 6 | P=0.079N | P=0.468N | |LOGISTIC REGRESSION| P=0.026N* | P=0.477N | |COCH-ARM / FISHERS | P=0.059N | P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 20/50 (40%) 20/50 (40%) | 16/50 (32%) 12/50 (24%) | |POLY-3 RATE (b) | 20/48.80 20/47.73 | 16/43.96 12/46.22 | |POLY-3 PERCENT (g) | 41.0% 41.9% | 36.4% 26.0% | |TERMINAL (d) | 20/48 (42%) 17/43 (40%) | 16/40 (40%) 12/41 (29%) | |FIRST INCIDENCE | 727 (T) 530 | 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.414 | P=0.219N | |POLY 3 | P=0.546 | P=0.198N | |POLY 1.5 | P=0.548 | P=0.205N | |POLY 6 | P=0.546 | P=0.197N | |LOGISTIC REGRESSION| P=0.538 | P=0.219N | |COCH-ARM / FISHERS | P=0.581N | P=0.252N | |=================================================================================================================================| Date: 12/19/00 EXPERIMENT: 56348 TEST: 04 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 14/50 (28%) 18/50 (36%) | 12/50 (24%) 12/50 (24%) | |POLY-3 RATE (b) | 14/50.00 18/47.37 | 12/44.55 12/47.13 | |POLY-3 PERCENT (g) | 28.0% 38.0% | 26.9% 25.5% | |TERMINAL (d) | 12/48 (25%) 16/43 (37%) | 11/40 (28%) 7/41 (17%) | |FIRST INCIDENCE | 397 530 | 545 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.171 | P=0.556N | |POLY 3 | P=0.205 | P=0.528N | |POLY 1.5 | P=0.217 | P=0.539N | |POLY 6 | P=0.193 | P=0.519N | |LOGISTIC REGRESSION| P=0.278 | P=0.551N | |COCH-ARM / FISHERS | P=0.260 | P=0.592N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 27/50 (54%) 28/50 (56%) | 23/50 (46%) 22/50 (44%) | |POLY-3 RATE (b) | 27/50.00 28/47.73 | 23/44.55 22/47.13 | |POLY-3 PERCENT (g) | 54.0% 58.7% | 51.6% 46.7% | |TERMINAL (d) | 25/48 (52%) 25/43 (58%) | 22/40 (55%) 17/41 (42%) | |FIRST INCIDENCE | 397 530 | 545 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.294 | P=0.451N | |POLY 3 | P=0.400 | P=0.394N | |POLY 1.5 | P=0.419 | P=0.412N | |POLY 6 | P=0.384 | P=0.378N | |LOGISTIC REGRESSION| P=0.474 | P=0.409N | |COCH-ARM / FISHERS | P=0.500 | P=0.500N | |=================================================================================================================================| (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).