TDMS Study 56348-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus CITRAL DATE: 06/01/00 EXPERIMENT: 56348 TEST: 03 TIME: 12:39:05 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: SINGER, ALLEN CAS: 5392-40-5 Rats(FISCHER 344) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Kidney Lung Nose Pancreas Parathyroid Gland Pituitary Gland Testes Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus CITRAL DATE: 06/01/00 EXPERIMENT: 56348 TEST: 03 TIME: 12:39:05 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: SINGER, ALLEN CAS: 5392-40-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF CITRAL =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Thyroid Gland: Follicular Cell Carcinoma or Adenoma =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Uterus Polyp Stromal =============================================================== Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 1 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) | 2/49 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 13.6% 9.5% | 4.5% 2.1% | |TERMINAL (d) | 3/30 (10%) 2/22 (9%) | 2/34 (6%) 0/40 (0%) | |FIRST INCIDENCE | 639 610 | 732 (T) 708 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.491N | P=0.451N | |POLY 3 | P=0.402N | P=0.470N | |POLY 1.5 | P=0.388N | P=0.483N | |POLY 6 | P=0.426N | P=0.453N | |LOGISTIC REGRESSION| P=0.383N | P=0.465N | |COCH-ARM / FISHERS | P=0.370N | P=0.492N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 4/50 (8%) | 2/49 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 15.8% 9.5% | 4.5% 2.1% | |TERMINAL (d) | 4/30 (13%) 2/22 (9%) | 2/34 (6%) 0/40 (0%) | |FIRST INCIDENCE | 639 610 | 732 (T) 708 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.387N | P=0.451N | |POLY 3 | P=0.290N | P=0.470N | |POLY 1.5 | P=0.278N | P=0.483N | |POLY 6 | P=0.312N | P=0.453N | |LOGISTIC REGRESSION| P=0.278N | P=0.465N | |COCH-ARM / FISHERS | P=0.262N | P=0.492N | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 2 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) | 9/49 (18%) 6/49 (12%) | |POLY-3 ADJUSTED (b)| 9.2% 7.1% | 20.2% 13.0% | |TERMINAL (d) | 3/30 (10%) 1/22 (5%) | 8/35 (23%) 5/40 (13%) | |FIRST INCIDENCE | 660 639 | 719 708 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.612N | P=0.208N | |POLY 3 | P=0.524N | P=0.259N | |POLY 1.5 | P=0.514N | P=0.278N | |POLY 6 | P=0.540N | P=0.235N | |LOGISTIC REGRESSION| P=0.527N | P=0.218N | |COCH-ARM / FISHERS | P=0.500N | P=0.288N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) | 9/49 (18%) 7/49 (14%) | |POLY-3 ADJUSTED (b)| 11.3% 7.1% | 20.2% 15.1% | |TERMINAL (d) | 3/30 (10%) 1/22 (5%) | 8/35 (23%) 6/40 (15%) | |FIRST INCIDENCE | 617 639 | 719 708 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.458N | P=0.295N | |POLY 3 | P=0.385N | P=0.359N | |POLY 1.5 | P=0.373N | P=0.381N | |POLY 6 | P=0.405N | P=0.331N | |LOGISTIC REGRESSION| P=0.367N | P=0.309N | |COCH-ARM / FISHERS | P=0.357N | P=0.393N | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 3 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.3% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 2/22 (9%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 674 726 (T) | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.415 | (e) | |POLY 3 | P=0.493 | (e) | |POLY 1.5 | P=0.498 | (e) | |POLY 6 | P=0.485 | (e) | |LOGISTIC REGRESSION| P=0.474 | (e) | |COCH-ARM / FISHERS | P=0.508 | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) | 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% | 0.0% 4.2% | |TERMINAL (d) | 0/30 (0%) 0/22 (0%) | 0/35 (0%) 2/40 (5%) | |FIRST INCIDENCE | --- --- | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) | P=0.268 | |POLY 3 | (e) | P=0.242 | |POLY 1.5 | (e) | P=0.239 | |POLY 6 | (e) | P=0.246 | |LOGISTIC REGRESSION| (e) | P=0.268 | |COCH-ARM / FISHERS | (e) | P=0.247 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 4 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 2/50 (4%) 1/50 (2%) | 1/50 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.6% 2.4% | 2.2% 2.1% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 1/35 (3%) 0/40 (0%) | |FIRST INCIDENCE | 695 637 | 732 (T) 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.558N | P=0.729N | |POLY 3 | P=0.518N | P=0.746N | |POLY 1.5 | P=0.510N | P=0.755N | |POLY 6 | P=0.530N | P=0.734N | |LOGISTIC REGRESSION| P=0.504N | P=0.761N | |COCH-ARM / FISHERS | P=0.500N | P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) | 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 4.6% 2.4% | 2.2% 4.2% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 1/35 (3%) 0/40 (0%) | |FIRST INCIDENCE | 695 637 | 732 (T) 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.558N | P=0.546 | |POLY 3 | P=0.518N | P=0.511 | |POLY 1.5 | P=0.510N | P=0.504 | |POLY 6 | P=0.530N | P=0.521 | |LOGISTIC REGRESSION| P=0.504N | P=0.501 | |COCH-ARM / FISHERS | P=0.500N | P=0.500 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 5 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 695 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.189 | (e) | |POLY 3 | P=0.233 | (e) | |POLY 1.5 | P=0.235 | (e) | |POLY 6 | P=0.230 | (e) | |LOGISTIC REGRESSION| P=0.215 | (e) | |COCH-ARM / FISHERS | P=0.247 | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.3% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 688 695 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.431 | (e) | |POLY 3 | P=0.490 | (e) | |POLY 1.5 | P=0.494 | (e) | |POLY 6 | P=0.483 | (e) | |LOGISTIC REGRESSION| P=0.478 | (e) | |COCH-ARM / FISHERS | P=0.500 | (e) | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 6 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/50 (10%) | 26/50 (52%) 27/50 (54%) | |POLY-3 ADJUSTED (b)| 6.9% 12.0% | 56.7% 56.6% | |TERMINAL (d) | 3/30 (10%) 4/22 (18%) | 21/35 (60%) 22/40 (55%) | |FIRST INCIDENCE | 726 (T) 695 | 609 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.207 | P=0.406N | |POLY 3 | P=0.336 | P=0.576N | |POLY 1.5 | P=0.345 | P=0.531 | |POLY 6 | P=0.323 | P=0.496N | |LOGISTIC REGRESSION| P=0.246 | P=0.461N | |COCH-ARM / FISHERS | P=0.357 | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) | 26/50 (52%) 27/50 (54%) | |POLY-3 ADJUSTED (b)| 9.2% 12.0% | 56.7% 56.6% | |TERMINAL (d) | 3/30 (10%) 4/22 (18%) | 21/35 (60%) 22/40 (55%) | |FIRST INCIDENCE | 688 695 | 609 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.333 | P=0.406N | |POLY 3 | P=0.476 | P=0.576N | |POLY 1.5 | P=0.486 | P=0.531 | |POLY 6 | P=0.459 | P=0.496N | |LOGISTIC REGRESSION| P=0.401 | P=0.461N | |COCH-ARM / FISHERS | P=0.500 | P=0.500 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 7 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 7/50 (14%) | 26/50 (52%) 27/50 (54%) | |POLY-3 ADJUSTED (b)| 9.2% 16.7% | 56.7% 56.6% | |TERMINAL (d) | 3/30 (10%) 5/22 (23%) | 21/35 (60%) 22/40 (55%) | |FIRST INCIDENCE | 688 695 | 609 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.133 | P=0.406N | |POLY 3 | P=0.238 | P=0.576N | |POLY 1.5 | P=0.248 | P=0.531 | |POLY 6 | P=0.222 | P=0.496N | |LOGISTIC REGRESSION| P=0.180 | P=0.461N | |COCH-ARM / FISHERS | P=0.262 | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Parathyroid Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/45 (0%) | 2/43 (5%) 0/43 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% | 5.2% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/19 (0%) | 2/29 (7%) 0/35 (0%) | |FIRST INCIDENCE | --- --- | 732 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) | P=0.198N | |POLY 3 | (e) | P=0.219N | |POLY 1.5 | (e) | P=0.230N | |POLY 6 | (e) | P=0.205N | |LOGISTIC REGRESSION| (e) | (e) | |COCH-ARM / FISHERS | (e) | P=0.247N | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 8 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 8/50 (16%) 9/50 (18%) | 12/50 (24%) 17/50 (34%) | |POLY-3 ADJUSTED (b)| 18.4% 21.3% | 26.2% 35.8% | |TERMINAL (d) | 7/30 (23%) 5/22 (23%) | 8/35 (23%) 14/40 (35%) | |FIRST INCIDENCE | 688 660 | 609 677 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.278 | P=0.317 | |POLY 3 | P=0.473 | P=0.218 | |POLY 1.5 | P=0.484 | P=0.197 | |POLY 6 | P=0.457 | P=0.248 | |LOGISTIC REGRESSION| P=0.392 | P=0.245 | |COCH-ARM / FISHERS | P=0.500 | P=0.189 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 9/50 (18%) | 12/50 (24%) 17/50 (34%) | |POLY-3 ADJUSTED (b)| 18.4% 21.3% | 26.2% 35.8% | |TERMINAL (d) | 7/30 (23%) 5/22 (23%) | 8/35 (23%) 14/40 (35%) | |FIRST INCIDENCE | 688 660 | 609 677 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.278 | P=0.317 | |POLY 3 | P=0.473 | P=0.218 | |POLY 1.5 | P=0.484 | P=0.197 | |POLY 6 | P=0.457 | P=0.248 | |LOGISTIC REGRESSION| P=0.392 | P=0.245 | |COCH-ARM / FISHERS | P=0.500 | P=0.189 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 9 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor | | (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 7/50 (14%) 4/50 (8%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 15.8% 9.5% | 0.0% 2.1% | |TERMINAL (d) | 5/30 (17%) 2/22 (9%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 505 617 | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.394N | P=0.527 | |POLY 3 | P=0.293N | P=0.500 | |POLY 1.5 | P=0.280N | P=0.500 | |POLY 6 | P=0.312N | P=0.501 | |LOGISTIC REGRESSION| P=0.263N | P=0.527 | |COCH-ARM / FISHERS | P=0.262N | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Fibroma or Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 6.8% 2.4% | 0.0% 2.1% | |TERMINAL (d) | 2/30 (7%) 1/22 (5%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 610 726 (T) | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.389N | P=0.527 | |POLY 3 | P=0.329N | P=0.500 | |POLY 1.5 | P=0.319N | P=0.500 | |POLY 6 | P=0.346N | P=0.501 | |LOGISTIC REGRESSION| P=0.319N | P=0.527 | |COCH-ARM / FISHERS | P=0.309N | P=0.500 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 10 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 9.1% 9.4% | 0.0% 2.1% | |TERMINAL (d) | 2/30 (7%) 1/22 (5%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 610 365 | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.542 | P=0.527 | |POLY 3 | P=0.628 | P=0.500 | |POLY 1.5 | P=0.635 | P=0.500 | |POLY 6 | P=0.613 | P=0.501 | |LOGISTIC REGRESSION| P=0.609N | P=0.527 | |COCH-ARM / FISHERS | P=0.643N | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.6% 0.0% | 0.0% 0.0% | |TERMINAL (d) | 2/30 (7%) 0/22 (0%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 726 (T) --- | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.308N | (e) | |POLY 3 | P=0.252N | (e) | |POLY 1.5 | P=0.246N | (e) | |POLY 6 | P=0.262N | (e) | |LOGISTIC REGRESSION| (e) | (e) | |COCH-ARM / FISHERS | P=0.247N | (e) | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 11 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 3/50 (6%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.9% 4.7% | 0.0% 0.0% | |TERMINAL (d) | 2/30 (7%) 0/22 (0%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 674 365 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.577N | (e) | |POLY 3 | P=0.513N | (e) | |POLY 1.5 | P=0.506N | (e) | |POLY 6 | P=0.527N | (e) | |LOGISTIC REGRESSION| P=0.447N | (e) | |COCH-ARM / FISHERS | P=0.500N | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 11.3% 7.1% | 0.0% 0.0% | |TERMINAL (d) | 3/30 (10%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 505 617 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.455N | (e) | |POLY 3 | P=0.388N | (e) | |POLY 1.5 | P=0.375N | (e) | |POLY 6 | P=0.408N | (e) | |LOGISTIC REGRESSION| P=0.336N | (e) | |COCH-ARM / FISHERS | P=0.357N | (e) | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 12 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Lipoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) | 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% | 4.4% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/22 (0%) | 1/35 (3%) 0/40 (0%) | |FIRST INCIDENCE | --- --- | 588 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) | P=0.225N | |POLY 3 | (e) | P=0.227N | |POLY 1.5 | (e) | P=0.234N | |POLY 6 | (e) | P=0.218N | |LOGISTIC REGRESSION| (e) | P=0.222N | |COCH-ARM / FISHERS | (e) | P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.7% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/22 (0%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 628 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.242 | (e) | |POLY 3 | P=0.234 | (e) | |POLY 1.5 | P=0.235 | (e) | |POLY 6 | P=0.232 | (e) | |LOGISTIC REGRESSION| P=0.265 | (e) | |COCH-ARM / FISHERS | P=0.247 | (e) | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 13 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell | | Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 3/50 (6%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 13.5% 7.1% | 0.0% 2.1% | |TERMINAL (d) | 4/30 (13%) 1/22 (5%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 505 617 | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.345N | P=0.527 | |POLY 3 | P=0.270N | P=0.500 | |POLY 1.5 | P=0.259N | P=0.500 | |POLY 6 | P=0.287N | P=0.501 | |LOGISTIC REGRESSION| P=0.232N | P=0.527 | |COCH-ARM / FISHERS | P=0.243N | P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 3/50 (6%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 13.5% 7.1% | 0.0% 2.1% | |TERMINAL (d) | 4/30 (13%) 1/22 (5%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 505 617 | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.345N | P=0.527 | |POLY 3 | P=0.270N | P=0.500 | |POLY 1.5 | P=0.259N | P=0.500 | |POLY 6 | P=0.287N | P=0.501 | |LOGISTIC REGRESSION| P=0.232N | P=0.527 | |COCH-ARM / FISHERS | P=0.243N | P=0.500 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 14 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 49/50 (98%) 47/50 (94%) | | |POLY-3 ADJUSTED (b)| 99.5% 98.5% | | |TERMINAL (d) | 30/30 (100%) 22/22 (100%) | | |FIRST INCIDENCE | 505 532 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.153 | | |POLY 3 | P=0.857N | | |POLY 1.5 | P=0.522N | | |POLY 6 | P=1.000N | | |LOGISTIC REGRESSION| P=0.469N | | |COCH-ARM / FISHERS | P=0.309N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 5/50 (10%) | 8/50 (16%) 13/50 (26%) | |POLY-3 ADJUSTED (b)| 16.1% 11.9% | 17.7% 27.6% | |TERMINAL (d) | 7/30 (23%) 3/22 (14%) | 7/35 (20%) 13/40 (33%) | |FIRST INCIDENCE | 726 (T) 623 | 719 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.573N | P=0.252 | |POLY 3 | P=0.402N | P=0.185 | |POLY 1.5 | P=0.393N | P=0.170 | |POLY 6 | P=0.416N | P=0.207 | |LOGISTIC REGRESSION| P=0.467N | P=0.230 | |COCH-ARM / FISHERS | P=0.380N | P=0.163 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 15 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.6% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 2/30 (7%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 726 (T) 688 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.596 | (e) | |POLY 3 | P=0.684 | (e) | |POLY 1.5 | P=0.688 | (e) | |POLY 6 | P=0.678 | (e) | |LOGISTIC REGRESSION| P=0.646 | (e) | |COCH-ARM / FISHERS | P=0.691N | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 7/50 (14%) | 8/50 (16%) 13/50 (26%) | |POLY-3 ADJUSTED (b)| 20.7% 16.6% | 17.7% 27.6% | |TERMINAL (d) | 9/30 (30%) 4/22 (18%) | 7/35 (20%) 13/40 (33%) | |FIRST INCIDENCE | 726 (T) 623 | 719 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.599 | P=0.252 | |POLY 3 | P=0.416N | P=0.185 | |POLY 1.5 | P=0.407N | P=0.170 | |POLY 6 | P=0.429N | P=0.207 | |LOGISTIC REGRESSION| P=0.500N | P=0.230 | |COCH-ARM / FISHERS | P=0.393N | P=0.163 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 16 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.8% 0.0% | 0.0% 0.0% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 450 --- | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.165N | (e) | |POLY 3 | P=0.134N | (e) | |POLY 1.5 | P=0.128N | (e) | |POLY 6 | P=0.144N | (e) | |LOGISTIC REGRESSION| P=0.093N | (e) | |COCH-ARM / FISHERS | P=0.121N | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) | 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 9.0% 0.0% | 0.0% 2.1% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 450 --- | --- 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.087N | P=0.527 | |POLY 3 | P=0.072N | P=0.500 | |POLY 1.5 | P=0.067N | P=0.500 | |POLY 6 | P=0.080N | P=0.501 | |LOGISTIC REGRESSION| P=0.042N* | P=0.527 | |COCH-ARM / FISHERS | P=0.059N | P=0.500 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 17 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | | 14/50 (28%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| | 30.5% 10.6% | |TERMINAL (d) | | 12/35 (34%) 5/40 (13%) | |FIRST INCIDENCE | | 508 732 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | | P=0.010N* | |POLY 3 | | P=0.015N* | |POLY 1.5 | | P=0.017N* | |POLY 6 | | P=0.012N* | |LOGISTIC REGRESSION| | P=0.015N* | |COCH-ARM / FISHERS | | P=0.020N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) | 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% | 0.0% 4.2% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 726 (T) --- | --- 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.562N | P=0.273 | |POLY 3 | P=0.518N | P=0.243 | |POLY 1.5 | P=0.510N | P=0.239 | |POLY 6 | P=0.530N | P=0.247 | |LOGISTIC REGRESSION| (e) | P=0.238 | |COCH-ARM / FISHERS | P=0.500N | P=0.247 | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 18 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) | 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% | 0.0% 4.2% | |TERMINAL (d) | 1/30 (3%) 0/22 (0%) | 0/35 (0%) 1/40 (3%) | |FIRST INCIDENCE | 726 (T) --- | --- 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.562N | P=0.273 | |POLY 3 | P=0.518N | P=0.243 | |POLY 1.5 | P=0.510N | P=0.239 | |POLY 6 | P=0.530N | P=0.247 | |LOGISTIC REGRESSION| (e) | P=0.238 | |COCH-ARM / FISHERS | P=0.500N | P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or | | Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 33/50 (66%) 35/50 (70%) | 14/50 (28%) 10/50 (20%) | |POLY-3 ADJUSTED (b)| 68.0% 75.3% | 28.8% 21.1% | |TERMINAL (d) | 16/30 (53%) 15/22 (68%) | 5/35 (14%) 9/40 (23%) | |FIRST INCIDENCE | 450 446 | 508 652 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.143 | P=0.175N | |POLY 3 | P=0.282 | P=0.264N | |POLY 1.5 | P=0.332 | P=0.262N | |POLY 6 | P=0.227 | P=0.266N | |LOGISTIC REGRESSION| P=0.396 | P=0.243N | |COCH-ARM / FISHERS | P=0.415 | P=0.241N | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 19 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.6% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 610 663 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.631 | (e) | |POLY 3 | P=0.682 | (e) | |POLY 1.5 | P=0.687 | (e) | |POLY 6 | P=0.673 | (e) | |LOGISTIC REGRESSION| P=0.693N | (e) | |COCH-ARM / FISHERS | P=0.691N | (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) | 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.6% 4.8% | 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/22 (5%) | 0/35 (0%) 0/40 (0%) | |FIRST INCIDENCE | 610 663 | --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.631 | (e) | |POLY 3 | P=0.682 | (e) | |POLY 1.5 | P=0.687 | (e) | |POLY 6 | P=0.673 | (e) | |LOGISTIC REGRESSION| P=0.693N | (e) | |COCH-ARM / FISHERS | P=0.691N | (e) | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 20 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 50/50 (100%) 47/50 (94%) | 37/50 (74%) 41/50 (82%) | |POLY-3 ADJUSTED (b)| 100.0% 98.5% | 78.8% 85.4% | |TERMINAL (d) | 30/30 (100%) 22/22 (100%) | 30/35 (86%) 34/40 (85%) | |FIRST INCIDENCE | 450 532 | 508 677 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.193 | P=0.519N | |POLY 3 | P=0.758N | P=0.272 | |POLY 1.5 | P=0.303N | P=0.221 | |POLY 6 | P=1.000N | P=0.380 | |LOGISTIC REGRESSION| P=0.165N | P=0.422 | |COCH-ARM / FISHERS | P=0.121N | P=0.235 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 35/50 (70%) 41/50 (82%) | 15/50 (30%) 15/50 (30%) | |POLY-3 ADJUSTED (b)| 71.5% 83.6% | 30.6% 31.1% | |TERMINAL (d) | 17/30 (57%) 15/22 (68%) | 5/35 (14%) 12/40 (30%) | |FIRST INCIDENCE | 450 365 | 508 491 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.059 | P=0.452N | |POLY 3 | P=0.112 | P=0.568 | |POLY 1.5 | P=0.115 | P=0.566 | |POLY 6 | P=0.110 | P=0.567 | |LOGISTIC REGRESSION| P=0.146 | P=0.557 | |COCH-ARM / FISHERS | P=0.121 | P=0.586N | |=================================================================================================================================| Date: 06/01/00 EXPERIMENT: 56348 TEST: 03 Page 21 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT VEHICLE | UNTREAT VEHICLE | | | CONTROL CONTROL | CONTROL CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | # # | |----------- | | | |OVERALL (a) | 50/50 (100%) 49/50 (98%) | 47/50 (94%) 45/50 (90%) | |POLY-3 ADJUSTED (b)| 100.0% 99.3% | 94.0% 91.8% | |TERMINAL (d) | 30/30 (100%) 22/22 (100%) | 32/35 (91%) 36/40 (90%) | |FIRST INCIDENCE | 450 365 | 508 491 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.126 | P=0.120N | |POLY 3 | P=0.971N | P=0.491N | |POLY 1.5 | P=0.759N | P=0.487N | |POLY 6 | P=1.000N | P=0.491N | |LOGISTIC REGRESSION| P=0.636N | P=0.383N | |COCH-ARM / FISHERS | P=0.500N | P=0.357N | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Poly-3 adjusted lifetime tumor incidence. (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).