TDMS Study 05211-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst EMODIN DATE: 12/02/98 EXPERIMENT: 05211 TEST: 06 TIME: 10:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-85216 ROUTE: DOSED FEED NTP C#: C62408 PATHOLOGIST: FARNELL, D. CAS: 518-82-1 ------------------------------------------------------------------------------------------------------------------------------------ CORE STUDY MICE REASONS FOR REMOVAL: 25022 Accidently Killed 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst EMODIN DATE: 12/02/98 EXPERIMENT: 05211 TEST: 06 TIME: 10:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-85216 ROUTE: DOSED FEED NTP C#: C62408 PATHOLOGIST: FARNELL, D. CAS: 518-82-1 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 Gallbladder Heart Islets, Pancreatic Kidney Liver Lung Ovary Pancreas Parathyroid Gland Pituitary Gland Spleen Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst EMODIN DATE: 12/02/98 EXPERIMENT: 05211 TEST: 06 TIME: 10:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-85216 ROUTE: DOSED FEED NTP C#: C62408 PATHOLOGIST: FARNELL, D. CAS: 518-82-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF EMODIN =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Adenoma Liver Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Thyroid Gland: Follicular Cell Carcinoma or Adenoma All Organs Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Malignant and Benign Tumors =============================================================== Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 6/50 (12%) 5/50 (10%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.1% 13.1% 10.7% 4.2% |0.0% 2.2% 0.0% 2.2% | |TERMINAL (d) | 1/41 (2%) 6/37 (16%) 5/40 (13%) 2/43 (5%) |0/37 (0%) 1/39 (3%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- 731 (T) --- 608 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.495N P=0.043 * P=0.097 P=0.517 |P=0.406 P=0.511 (e) P=0.509 | |POLY 3 | P=0.538N P=0.050 P=0.097 P=0.501 |P=0.412 P=0.502 (e) P=0.504 | |POLY 1.5 | P=0.543N P=0.052 P=0.099 P=0.499 |P=0.409 P=0.500 (e) P=0.502 | |POLY 6 | P=0.526N P=0.047 * P=0.096 P=0.506 |P=0.416 P=0.506 (e) P=0.506 | |LOGISTIC REGRESSION| P=0.495N P=0.043 * P=0.097 P=0.517 |P=0.403 P=0.511 (e) P=0.516 | |COCH-ARM / FISHERS | P=0.542N P=0.056 P=0.102 P=0.500 |P=0.405 P=0.500 (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 3/50 (6%) 4/50 (8%) |0/50 (0%) 3/50 (6%) 3/50 (6%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 8.4% 4.4% 6.4% 8.4% |0.0% 6.6% 6.4% 2.2% | |TERMINAL (d) | 3/41 (7%) 2/37 (5%) 3/40 (8%) 4/43 (9%) |0/37 (0%) 3/39 (8%) 3/40 (8%) 1/36 (3%) | |FIRST INCIDENCE | 639 729 (T) 729 (T) 729 (T) |--- 731 (T) 731 (T) 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.524 P=0.383N P=0.515N P=0.621N |P=0.512 P=0.130 P=0.135 P=0.495 | |POLY 3 | P=0.492 P=0.359N P=0.515N P=0.641 |P=0.532 P=0.120 P=0.127 P=0.502 | |POLY 1.5 | P=0.486 P=0.351N P=0.510N P=0.639 |P=0.529 P=0.119 P=0.122 P=0.501 | |POLY 6 | P=0.501 P=0.369N P=0.520N P=0.640N |P=0.536 P=0.124 P=0.134 P=0.503 | |LOGISTIC REGRESSION| P=0.501 P=0.348N P=0.508N P=0.643 |(e) P=0.130 P=0.135 P=0.495 | |COCH-ARM / FISHERS | P=0.483 P=0.339N P=0.500N P=0.643N |P=0.526 P=0.121 P=0.121 P=0.500 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 2.1% 6.3% |2.2% 0.0% 2.1% 4.3% | |TERMINAL (d) | 0/41 (0%) 0/37 (0%) 1/40 (3%) 3/43 (7%) |1/37 (3%) 0/39 (0%) 1/40 (3%) 1/36 (3%) | |FIRST INCIDENCE | --- 715 729 (T) 729 (T) |731 (T) --- 731 (T) 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.067 P=0.480 P=0.495 P=0.130 |P=0.242 P=0.489N P=0.744N P=0.499 | |POLY 3 | P=0.055 P=0.492 P=0.496 P=0.120 |P=0.252 P=0.498N P=0.751N P=0.507 | |POLY 1.5 | P=0.054 P=0.495 P=0.497 P=0.119 |P=0.251 P=0.500N P=0.757N P=0.503 | |POLY 6 | P=0.057 P=0.489 P=0.495 P=0.122 |P=0.252 P=0.494N P=0.742N P=0.511 | |LOGISTIC REGRESSION| P=0.062 P=0.494 P=0.495 P=0.130 |P=0.247 (e) P=0.744N P=0.498 | |COCH-ARM / FISHERS | P=0.054 P=0.500 P=0.500 P=0.121 |P=0.247 P=0.500N P=0.753N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 4/50 (8%) 7/50 (14%) |1/50 (2%) 3/50 (6%) 4/50 (8%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 8.4% 6.6% 8.6% 14.7% |2.2% 6.6% 8.5% 6.5% | |TERMINAL (d) | 3/41 (7%) 2/37 (5%) 4/40 (10%) 7/43 (16%) |1/37 (3%) 3/39 (8%) 4/40 (10%) 2/36 (6%) | |FIRST INCIDENCE | 639 715 729 (T) 729 (T) |731 (T) 731 (T) 731 (T) 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.176 P=0.552N P=0.628 P=0.287 |P=0.267 P=0.324 P=0.203 P=0.303 | |POLY 3 | P=0.144 P=0.525N P=0.628 P=0.260 |P=0.293 P=0.308 P=0.192 P=0.312 | |POLY 1.5 | P=0.141 P=0.515N P=0.633 P=0.258 |P=0.289 P=0.306 P=0.184 P=0.309 | |POLY 6 | P=0.150 P=0.536N P=0.623 P=0.265 |P=0.299 P=0.315 P=0.204 P=0.316 | |LOGISTIC REGRESSION| P=0.156 P=0.514N P=0.634 P=0.263 |P=0.286 P=0.324 P=0.203 P=0.304 | |COCH-ARM / FISHERS | P=0.140 P=0.500N P=0.643N P=0.262 |P=0.282 P=0.309 P=0.181 P=0.309 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Intestine Small: Jejunum | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 4/50 (8%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 8.6% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/41 (0%) 0/37 (0%) 4/40 (10%) 0/43 (0%) |0/37 (0%) 0/39 (0%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.529 (e) P=0.060 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.518 (e) P=0.058 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.509 (e) P=0.059 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.532 (e) P=0.057 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.060 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.505 (e) P=0.059 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Intestine Small: Site Unspecified | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 4/50 (8%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 8.6% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/41 (0%) 0/37 (0%) 4/40 (10%) 0/43 (0%) |0/37 (0%) 0/39 (0%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.529 (e) P=0.060 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.518 (e) P=0.058 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.509 (e) P=0.059 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.532 (e) P=0.057 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.060 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.505 (e) P=0.059 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 4.3% 2.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/41 (0%) 1/37 (3%) 2/40 (5%) 1/43 (2%) |0/37 (0%) 0/39 (0%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.392 P=0.480 P=0.233 P=0.510 |(e) (e) (e) (e) | |POLY 3 | P=0.377 P=0.496 P=0.237 P=0.504 |(e) (e) (e) (e) | |POLY 1.5 | P=0.372 P=0.499 P=0.239 P=0.503 |(e) (e) (e) (e) | |POLY 6 | P=0.385 P=0.492 P=0.235 P=0.507 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.480 P=0.233 P=0.510 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.371 P=0.505 P=0.253 P=0.505 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 6.2% 0.0% 2.1% 2.1% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 2/41 (5%) 0/37 (0%) 1/40 (3%) 0/43 (0%) |0/37 (0%) 0/39 (0%) 0/40 (0%) 1/36 (3%) | |FIRST INCIDENCE | 556 --- 729 (T) 604 |--- --- --- 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.284N P=0.139N P=0.317N P=0.301N |P=0.191 (e) (e) P=0.495 | |POLY 3 | P=0.284N P=0.128N P=0.317N P=0.305N |P=0.200 (e) (e) P=0.502 | |POLY 1.5 | P=0.288N P=0.125N P=0.313N P=0.307N |P=0.200 (e) (e) P=0.501 | |POLY 6 | P=0.278N P=0.133N P=0.320N P=0.300N |P=0.199 (e) (e) P=0.503 | |LOGISTIC REGRESSION| P=0.259N P=0.076N P=0.257N P=0.233N |(e) (e) (e) P=0.495 | |COCH-ARM / FISHERS | P=0.293N P=0.121N P=0.309N P=0.309N |P=0.198 (e) (e) P=0.500 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 10/50 (20%) 12/50 (24%) 11/50 (22%) |9/50 (18%) 7/50 (14%) 12/50 (24%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 18.9% 21.9% 25.4% 23.1% |19.9% 15.3% 25.4% 15.3% | |TERMINAL (d) | 9/41 (22%) 10/37 (27%) 11/40 (28%) 11/43 (26%) |9/37 (24%) 5/39 (13%) 12/40 (30%) 5/36 (14%) | |FIRST INCIDENCE | 729 (T) 729 (T) 497 729 (T) |731 (T) 720 731 (T) 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.422 P=0.399 P=0.289 P=0.447 |P=0.469N P=0.347N P=0.382 P=0.412N | |POLY 3 | P=0.357 P=0.461 P=0.305 P=0.405 |P=0.421N P=0.383N P=0.351 P=0.379N | |POLY 1.5 | P=0.346 P=0.476 P=0.307 P=0.399 |P=0.428N P=0.391N P=0.327 P=0.386N | |POLY 6 | P=0.379 P=0.445 P=0.306 P=0.418 |P=0.414N P=0.365N P=0.387 P=0.368N | |LOGISTIC REGRESSION| P=0.381 P=0.399 P=0.295 P=0.447 |P=0.431N P=0.331N P=0.382 P=0.379N | |COCH-ARM / FISHERS | P=0.341 P=0.500 P=0.312 P=0.402 |P=0.438N P=0.393N P=0.312 P=0.393N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 20/50 (40%) 25/50 (50%) 22/50 (44%) 16/50 (32%) |4/50 (8%) 7/50 (14%) 9/50 (18%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 41.1% 50.5% 44.0% 32.9% |8.8% 15.4% 19.1% 8.7% | |TERMINAL (d) | 15/41 (37%) 15/37 (41%) 12/40 (30%) 13/43 (30%) |3/37 (8%) 7/39 (18%) 9/40 (23%) 3/36 (8%) | |FIRST INCIDENCE | 636 446 497 632 |684 731 (T) 731 (T) 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.124N P=0.150 P=0.393 P=0.242N |P=0.523N P=0.292 P=0.150 P=0.637 | |POLY 3 | P=0.141N P=0.231 P=0.465 P=0.267N |P=0.487N P=0.263 P=0.131 P=0.637N | |POLY 1.5 | P=0.145N P=0.223 P=0.446 P=0.272N |P=0.493N P=0.260 P=0.121 P=0.640N | |POLY 6 | P=0.130N P=0.243 P=0.494 P=0.254N |P=0.481N P=0.272 P=0.145 P=0.633N | |LOGISTIC REGRESSION| P=0.156N P=0.291 P=0.485 P=0.266N |P=0.489N P=0.287 P=0.161 P=0.639N | |COCH-ARM / FISHERS | P=0.139N P=0.211 P=0.420 P=0.266N |P=0.500N P=0.262 P=0.117 P=0.643N | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 21/50 (42%) 25/50 (50%) 22/50 (44%) 16/50 (32%) |4/50 (8%) 7/50 (14%) 9/50 (18%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 43.2% 50.5% 44.0% 32.9% |8.8% 15.4% 19.1% 8.7% | |TERMINAL (d) | 16/41 (39%) 15/37 (41%) 12/40 (30%) 13/43 (30%) |3/37 (8%) 7/39 (18%) 9/40 (23%) 3/36 (8%) | |FIRST INCIDENCE | 636 446 497 632 |684 731 (T) 731 (T) 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.097N P=0.192 P=0.461 P=0.186N |P=0.523N P=0.292 P=0.150 P=0.637 | |POLY 3 | P=0.106N P=0.299 P=0.547 P=0.204N |P=0.487N P=0.263 P=0.131 P=0.637N | |POLY 1.5 | P=0.110N P=0.288 P=0.526 P=0.209N |P=0.493N P=0.260 P=0.121 P=0.640N | |POLY 6 | P=0.098N P=0.312 P=0.576 P=0.192N |P=0.481N P=0.272 P=0.145 P=0.633N | |LOGISTIC REGRESSION| P=0.118N P=0.363 P=0.567 P=0.204N |P=0.489N P=0.287 P=0.161 P=0.639N | |COCH-ARM / FISHERS | P=0.105N P=0.274 P=0.500 P=0.204N |P=0.500N P=0.262 P=0.117 P=0.643N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 28/50 (56%) 32/50 (64%) 31/50 (62%) 22/50 (44%) |13/50 (26%) 14/50 (28%) 21/50 (42%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 57.5% 64.7% 62.0% 45.3% |28.7% 30.7% 44.5% 23.8% | |TERMINAL (d) | 23/41 (56%) 22/37 (60%) 21/40 (53%) 19/43 (44%) |12/37 (32%) 12/39 (31%) 21/40 (53%) 8/36 (22%) | |FIRST INCIDENCE | 636 446 497 632 |684 720 731 (T) 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.065N P=0.162 P=0.320 P=0.135N |P=0.448N P=0.566 P=0.103 P=0.428N | |POLY 3 | P=0.078N P=0.302 P=0.403 P=0.156N |P=0.374N P=0.508 P=0.083 P=0.386N | |POLY 1.5 | P=0.082N P=0.289 P=0.376 P=0.163N |P=0.388N P=0.499 P=0.072 P=0.397N | |POLY 6 | P=0.069N P=0.320 P=0.443 P=0.142N |P=0.358N P=0.529 P=0.102 P=0.371N | |LOGISTIC REGRESSION| P=0.082N P=0.316 P=0.376 P=0.161N |P=0.386N P=0.576 P=0.142 P=0.388N | |COCH-ARM / FISHERS | P=0.078N P=0.270 P=0.342 P=0.159N |P=0.407N P=0.500 P=0.069 P=0.408N | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 32/50 (64%) 31/50 (62%) 22/50 (44%) |13/50 (26%) 14/50 (28%) 21/50 (42%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 59.6% 64.7% 62.0% 45.3% |28.7% 30.7% 44.5% 23.8% | |TERMINAL (d) | 24/41 (59%) 22/37 (60%) 21/40 (53%) 19/43 (44%) |12/37 (32%) 12/39 (31%) 21/40 (53%) 8/36 (22%) | |FIRST INCIDENCE | 636 446 497 632 |684 720 731 (T) 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049N* P=0.204 P=0.382 P=0.098N |P=0.448N P=0.566 P=0.103 P=0.428N | |POLY 3 | P=0.055N P=0.378 P=0.485 P=0.111N |P=0.374N P=0.508 P=0.083 P=0.386N | |POLY 1.5 | P=0.059N P=0.362 P=0.456 P=0.117N |P=0.388N P=0.499 P=0.072 P=0.397N | |POLY 6 | P=0.048N* P=0.399 P=0.527 P=0.100N |P=0.358N P=0.529 P=0.102 P=0.371N | |LOGISTIC REGRESSION| P=0.059N P=0.389 P=0.455 P=0.117N |P=0.386N P=0.576 P=0.142 P=0.388N | |COCH-ARM / FISHERS | P=0.056N P=0.341 P=0.419 P=0.115N |P=0.407N P=0.500 P=0.069 P=0.408N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 9/50 (18%) 6/50 (12%) 7/50 (14%) |4/50 (8%) 1/50 (2%) 2/50 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 18.9% 19.5% 12.7% 14.7% |8.7% 2.2% 4.2% 2.2% | |TERMINAL (d) | 8/41 (20%) 7/37 (19%) 5/40 (13%) 7/43 (16%) |2/37 (5%) 1/39 (3%) 2/40 (5%) 0/36 (0%) | |FIRST INCIDENCE | 699 636 572 729 (T) |592 731 (T) 731 (T) 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.239N P=0.510 P=0.307N P=0.353N |P=0.167N P=0.174N P=0.307N P=0.183N | |POLY 3 | P=0.281N P=0.571 P=0.296N P=0.392N |P=0.163N P=0.182N P=0.326N P=0.180N | |POLY 1.5 | P=0.288N P=0.582 P=0.294N P=0.396N |P=0.164N P=0.182N P=0.335N P=0.180N | |POLY 6 | P=0.270N P=0.561 P=0.296N P=0.381N |P=0.164N P=0.179N P=0.315N P=0.181N | |LOGISTIC REGRESSION| P=0.274N P=0.551 P=0.298N P=0.357N |P=0.166N P=0.172N P=0.335N P=0.178N | |COCH-ARM / FISHERS | P=0.289N P=0.602N P=0.288N P=0.393N |P=0.165N P=0.181N P=0.339N P=0.181N | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 9/50 (18%) 6/50 (12%) 5/50 (10%) |2/50 (4%) 1/50 (2%) 1/50 (2%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 20.9% 19.4% 12.8% 10.5% |4.4% 2.2% 2.1% 8.8% | |TERMINAL (d) | 8/41 (20%) 7/37 (19%) 5/40 (13%) 5/43 (12%) |1/37 (3%) 0/39 (0%) 1/40 (3%) 3/36 (8%) | |FIRST INCIDENCE | 680 632 688 729 (T) |548 727 731 (T) 709 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.064N P=0.588N P=0.224N P=0.115N |P=0.155 P=0.490N P=0.482N P=0.330 | |POLY 3 | P=0.078N P=0.532N P=0.221N P=0.131N |P=0.166 P=0.501N P=0.489N P=0.336 | |POLY 1.5 | P=0.080N P=0.520N P=0.216N P=0.133N |P=0.165 P=0.502N P=0.497N P=0.337 | |POLY 6 | P=0.074N P=0.543N P=0.224N P=0.127N |P=0.165 P=0.496N P=0.479N P=0.337 | |LOGISTIC REGRESSION| P=0.075N P=0.531N P=0.220N P=0.123N |P=0.165 P=0.486N P=0.490N P=0.335 | |COCH-ARM / FISHERS | P=0.080N P=0.500N P=0.207N P=0.131N |P=0.164 P=0.500N P=0.500N P=0.339 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 18/50 (36%) 17/50 (34%) 12/50 (24%) 10/50 (20%) |6/50 (12%) 2/50 (4%) 3/50 (6%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 37.6% 36.4% 25.4% 21.0% |12.9% 4.4% 6.4% 10.9% | |TERMINAL (d) | 16/41 (39%) 13/37 (35%) 10/40 (25%) 10/43 (23%) |3/37 (8%) 1/39 (3%) 3/40 (8%) 3/36 (8%) | |FIRST INCIDENCE | 680 632 572 729 (T) |548 727 731 (T) 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020N* P=0.524 P=0.159N P=0.044N* |P=0.557 P=0.132N P=0.217N P=0.506N | |POLY 3 | P=0.027N* P=0.536N P=0.143N P=0.057N |P=0.569N P=0.140N P=0.237N P=0.512N | |POLY 1.5 | P=0.029N* P=0.524N P=0.142N P=0.059N |P=0.570N P=0.139N P=0.243N P=0.507N | |POLY 6 | P=0.025N* P=0.544N P=0.142N P=0.053N |P=0.567 P=0.139N P=0.227N P=0.517N | |LOGISTIC REGRESSION| P=0.026N* P=0.567N P=0.152N P=0.045N* |P=0.568 P=0.124N P=0.238N P=0.505N | |COCH-ARM / FISHERS | P=0.030N* P=0.500N P=0.138N P=0.059N |P=0.570 P=0.134N P=0.243N P=0.500N | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |1/45 (2%) 2/44 (5%) 2/48 (4%) 1/48 (2%) | |POLY-3 ADJUSTED (b)| |2.4% 5.0% 4.4% 2.3% | |TERMINAL (d) | |1/35 (3%) 1/34 (3%) 2/39 (5%) 1/35 (3%) | |FIRST INCIDENCE | |731 (T) 681 731 (T) 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.547N P=0.502 P=0.538 P=0.762 | |POLY 3 | |P=0.518N P=0.489 P=0.539 P=0.744N | |POLY 1.5 | |P=0.521N P=0.489 P=0.529 P=0.744N | |POLY 6 | |P=0.518N P=0.491 P=0.549 P=0.744N | |LOGISTIC REGRESSION| |P=0.518N P=0.488 P=0.538 P=0.762 | |COCH-ARM / FISHERS | |P=0.526N P=0.491 P=0.524 P=0.736N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/40 (0%) 0/38 (0%) 0/42 (0%) 0/46 (0%) |4/46 (9%) 4/45 (9%) 9/46 (20%) 8/44 (18%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |9.7% 9.6% 20.7% 20.1% | |TERMINAL (d) | 0/34 (0%) 0/28 (0%) 0/34 (0%) 0/41 (0%) |4/34 (12%) 4/37 (11%) 9/39 (23%) 7/32 (22%) | |FIRST INCIDENCE | --- --- --- --- |731 (T) 731 (T) 731 (T) 709 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.060 P=0.598N P=0.172 P=0.149 | |POLY 3 | (e) (e) (e) (e) |P=0.075 P=0.640N P=0.133 P=0.156 | |POLY 1.5 | (e) (e) (e) (e) |P=0.075 P=0.638 P=0.121 P=0.156 | |POLY 6 | (e) (e) (e) (e) |P=0.074 P=0.625N P=0.152 P=0.158 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.060 P=0.598N P=0.172 P=0.148 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.076 P=0.631 P=0.115 P=0.156 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.1% 0.0% 0.0% 0.0% |4.4% 0.0% 2.1% 0.0% | |TERMINAL (d) | 1/41 (2%) 0/37 (0%) 0/40 (0%) 0/43 (0%) |1/37 (3%) 0/39 (0%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |587 --- 658 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.298N P=0.520N P=0.505N P=0.490N |P=0.185N P=0.239N P=0.473N P=0.243N | |POLY 3 | P=0.302N P=0.508N P=0.504N P=0.499N |P=0.187N P=0.238N P=0.486N P=0.237N | |POLY 1.5 | P=0.303N P=0.505N P=0.503N P=0.501N |P=0.187N P=0.238N P=0.495N P=0.238N | |POLY 6 | P=0.302N P=0.511N P=0.505N P=0.496N |P=0.188N P=0.234N P=0.474N P=0.237N | |LOGISTIC REGRESSION| P=0.298N (e) (e) (e) |P=0.185N P=0.221N P=0.483N P=0.235N | |COCH-ARM / FISHERS | P=0.304N P=0.500N P=0.500N P=0.500N |P=0.188N P=0.247N P=0.500N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 2.1% |4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/41 (0%) 1/37 (3%) 0/40 (0%) 1/43 (2%) |2/37 (5%) 0/39 (0%) 0/40 (0%) 0/36 (0%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |731 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.421 P=0.480 (e) P=0.510 |P=0.115N P=0.227N P=0.221N P=0.244N | |POLY 3 | P=0.403 P=0.492 (e) P=0.501 |P=0.113N P=0.235N P=0.228N P=0.235N | |POLY 1.5 | P=0.402 P=0.495 (e) P=0.499 |P=0.113N P=0.237N P=0.234N P=0.236N | |POLY 6 | P=0.407 P=0.489 (e) P=0.504 |P=0.114N P=0.231N P=0.220N P=0.234N | |LOGISTIC REGRESSION| (e) P=0.480 (e) P=0.510 |P=0.115N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.403 P=0.500 (e) P=0.500 |P=0.115N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 5/50 (10%) 2/50 (4%) 3/48 (6%) | |POLY-3 ADJUSTED (b)| 2.1% 11.0% 0.0% 0.0% |4.4% 11.0% 4.2% 6.7% | |TERMINAL (d) | 1/41 (2%) 5/37 (14%) 0/40 (0%) 0/43 (0%) |2/37 (5%) 5/39 (13%) 2/40 (5%) 3/36 (8%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |731 (T) 731 (T) 731 (T) 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.099N P=0.081 P=0.505N P=0.490N |P=0.563 P=0.237 P=0.667N P=0.487 | |POLY 3 | P=0.106N P=0.092 P=0.504N P=0.499N |P=0.577 P=0.220 P=0.678N P=0.494 | |POLY 1.5 | P=0.105N P=0.096 P=0.503N P=0.501N |P=0.569 P=0.217 P=0.688N P=0.489 | |POLY 6 | P=0.104N P=0.089 P=0.505N P=0.496N |P=0.577N P=0.227 P=0.665N P=0.499 | |LOGISTIC REGRESSION| P=0.099N P=0.081 (e) (e) |P=0.563 P=0.237 P=0.667N P=0.487 | |COCH-ARM / FISHERS | P=0.108N P=0.102 P=0.500N P=0.500N |P=0.559 P=0.218 P=0.691N P=0.480 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 5/50 (10%) 2/50 (4%) 3/48 (6%) | |POLY-3 ADJUSTED (b)| 4.2% 11.0% 0.0% 0.0% |4.4% 11.0% 4.2% 6.7% | |TERMINAL (d) | 2/41 (5%) 5/37 (14%) 0/40 (0%) 0/43 (0%) |2/37 (5%) 5/39 (13%) 2/40 (5%) 3/36 (8%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |731 (T) 731 (T) 731 (T) 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049N* P=0.176 P=0.244N P=0.228N |P=0.563 P=0.237 P=0.667N P=0.487 | |POLY 3 | P=0.052N P=0.200 P=0.242N P=0.236N |P=0.577 P=0.220 P=0.678N P=0.494 | |POLY 1.5 | P=0.052N P=0.207 P=0.240N P=0.238N |P=0.569 P=0.217 P=0.688N P=0.489 | |POLY 6 | P=0.051N P=0.193 P=0.243N P=0.233N |P=0.577N P=0.227 P=0.665N P=0.499 | |LOGISTIC REGRESSION| P=0.049N* P=0.176 (e) (e) |P=0.563 P=0.237 P=0.667N P=0.487 | |COCH-ARM / FISHERS | P=0.054N P=0.218 P=0.247N P=0.247N |P=0.559 P=0.218 P=0.691N P=0.480 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |2/50 (4%) 2/50 (4%) 2/50 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| |4.4% 4.4% 4.2% 4.4% | |TERMINAL (d) | |1/37 (3%) 1/39 (3%) 1/40 (3%) 1/36 (3%) | |FIRST INCIDENCE | |606 633 673 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.596 P=0.679N P=0.662N P=0.691 | |POLY 3 | |P=0.593N P=0.691N P=0.680N P=0.692N | |POLY 1.5 | |P=0.594N P=0.693 P=0.689N P=0.693N | |POLY 6 | |P=0.592N P=0.685N P=0.667N P=0.691N | |LOGISTIC REGRESSION| |P=0.595 P=0.686N P=0.693N P=0.693 | |COCH-ARM / FISHERS | |P=0.596 P=0.691N P=0.691N P=0.691N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.1% 0.0% 4.2% 0.0% |0.0% 0.0% 2.1% 0.0% | |TERMINAL (d) | 1/41 (2%) 0/37 (0%) 1/40 (3%) 0/43 (0%) |0/37 (0%) 0/39 (0%) 1/40 (3%) 0/36 (0%) | |FIRST INCIDENCE | 729 (T) --- 497 --- |--- --- 731 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.445N P=0.520N P=0.494 P=0.490N |P=0.693 (e) P=0.516 (e) | |POLY 3 | P=0.449N P=0.508N P=0.498 P=0.499N |P=0.694 (e) P=0.509 (e) | |POLY 1.5 | P=0.454N P=0.505N P=0.498 P=0.501N |P=0.695 (e) P=0.503 (e) | |POLY 6 | P=0.442N P=0.511N P=0.498 P=0.496N |P=0.693 (e) P=0.516 (e) | |LOGISTIC REGRESSION| P=0.405N (e) P=0.625 (e) |(e) (e) P=0.516 (e) | |COCH-ARM / FISHERS | P=0.458N P=0.500N P=0.500 P=0.500N |P=0.694 (e) P=0.500 (e) | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 6.2% 2.2% 4.3% 4.2% |2.2% 2.2% 4.2% 8.7% | |TERMINAL (d) | 2/41 (5%) 1/37 (3%) 2/40 (5%) 0/43 (0%) |1/37 (3%) 1/39 (3%) 0/40 (0%) 3/36 (8%) | |FIRST INCIDENCE | 556 729 (T) 729 (T) 604 |731 (T) 731 (T) 625 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.471N P=0.340N P=0.513N P=0.487N |P=0.071 P=0.750N P=0.535 P=0.180 | |POLY 3 | P=0.488N P=0.324N P=0.515N P=0.499N |P=0.074 P=0.759N P=0.520 P=0.183 | |POLY 1.5 | P=0.494N P=0.317N P=0.509N P=0.502N |P=0.073 P=0.760N P=0.508 P=0.181 | |POLY 6 | P=0.479N P=0.332N P=0.519N P=0.493N |P=0.075 P=0.754N P=0.535 P=0.187 | |LOGISTIC REGRESSION| P=0.487N P=0.255N P=0.465N P=0.440N |P=0.071 P=0.750N P=0.506 P=0.182 | |COCH-ARM / FISHERS | P=0.498N P=0.309N P=0.500N P=0.500N |P=0.072 P=0.753N P=0.500 P=0.181 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 4/50 (8%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 8.3% 2.2% 8.5% 4.2% |2.2% 2.2% 6.3% 8.7% | |TERMINAL (d) | 3/41 (7%) 1/37 (3%) 3/40 (8%) 0/43 (0%) |1/37 (3%) 1/39 (3%) 1/40 (3%) 3/36 (8%) | |FIRST INCIDENCE | 556 729 (T) 497 604 |731 (T) 731 (T) 625 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.367N P=0.211N P=0.629 P=0.326N |P=0.073 P=0.750N P=0.342 P=0.180 | |POLY 3 | P=0.379N P=0.195N P=0.633 P=0.337N |P=0.078 P=0.759N P=0.326 P=0.183 | |POLY 1.5 | P=0.387N P=0.189N P=0.636 P=0.340N |P=0.077 P=0.760N P=0.314 P=0.181 | |POLY 6 | P=0.366N P=0.202N P=0.631 P=0.330N |P=0.079 P=0.754N P=0.343 P=0.187 | |LOGISTIC REGRESSION| P=0.365N P=0.152N P=0.557N P=0.291N |P=0.075 P=0.750N P=0.305 P=0.182 | |COCH-ARM / FISHERS | P=0.393N P=0.181N P=0.643N P=0.339N |P=0.075 P=0.753N P=0.309 P=0.181 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 14 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 0.0% |2.2% 4.3% 10.4% 6.4% | |TERMINAL (d) | 0/41 (0%) 1/37 (3%) 0/40 (0%) 0/43 (0%) |0/37 (0%) 0/39 (0%) 2/40 (5%) 1/36 (3%) | |FIRST INCIDENCE | --- 729 (T) --- --- |608 490 461 445 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.560N P=0.480 (e) (e) |P=0.218 P=0.505 P=0.129 P=0.314 | |POLY 3 | P=0.578N P=0.492 (e) (e) |P=0.224 P=0.508 P=0.114 P=0.313 | |POLY 1.5 | P=0.576N P=0.495 (e) (e) |P=0.221 P=0.503 P=0.107 P=0.310 | |POLY 6 | P=0.579N P=0.489 (e) (e) |P=0.225 P=0.516 P=0.123 P=0.316 | |LOGISTIC REGRESSION| (e) P=0.480 (e) (e) |P=0.205 P=0.627 P=0.108 P=0.307 | |COCH-ARM / FISHERS | P=0.573N P=0.500 (e) (e) |P=0.216 P=0.500 P=0.102 P=0.309 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) 3/50 (6%) 1/50 (2%) |9/50 (18%) 10/50 (20%) 8/50 (16%) 10/50 (20%) | |POLY-3 ADJUSTED (b)| 10.5% 6.6% 6.4% 2.1% |19.4% 21.7% 16.9% 21.6% | |TERMINAL (d) | 5/41 (12%) 3/37 (8%) 2/40 (5%) 1/43 (2%) |5/37 (14%) 7/39 (18%) 6/40 (15%) 8/36 (22%) | |FIRST INCIDENCE | 729 (T) 729 (T) 727 729 (T) |606 659 698 608 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.069N P=0.413N P=0.371N P=0.093N |P=0.470 P=0.545 P=0.425N P=0.496 | |POLY 3 | P=0.076N P=0.379N P=0.368N P=0.101N |P=0.489 P=0.493 P=0.483N P=0.496 | |POLY 1.5 | P=0.078N P=0.371N P=0.364N P=0.103N |P=0.489 P=0.492 P=0.497N P=0.498 | |POLY 6 | P=0.072N P=0.388N P=0.370N P=0.097N |P=0.484 P=0.501 P=0.465N P=0.492 | |LOGISTIC REGRESSION| P=0.065N P=0.413N P=0.359N P=0.093N |P=0.493 P=0.500 P=0.496N P=0.500 | |COCH-ARM / FISHERS | P=0.079N P=0.357N P=0.357N P=0.102N |P=0.488 P=0.500 P=0.500N P=0.500 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 15 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 24/50 (48%) 27/50 (54%) 24/50 (48%) 22/50 (44%) |21/50 (42%) 23/50 (46%) 25/50 (50%) 19/50 (38%) | |POLY-3 ADJUSTED (b)| 49.7% 58.5% 50.3% 46.1% |44.7% 49.8% 52.8% 40.9% | |TERMINAL (d) | 21/41 (51%) 24/37 (65%) 21/40 (53%) 22/43 (51%) |17/37 (46%) 19/39 (49%) 24/40 (60%) 15/36 (42%) | |FIRST INCIDENCE | 636 636 497 729 (T) |587 633 673 608 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.178N P=0.182 P=0.530 P=0.342N |P=0.400N P=0.504 P=0.401 P=0.449N | |POLY 3 | P=0.289N P=0.254 P=0.559 P=0.442N |P=0.354N P=0.387 P=0.282 P=0.434N | |POLY 1.5 | P=0.297N P=0.289 P=0.567 P=0.441N |P=0.352N P=0.394 P=0.266 P=0.429N | |POLY 6 | P=0.273N P=0.217 P=0.551 P=0.438N |P=0.358N P=0.396 P=0.306 P=0.439N | |LOGISTIC REGRESSION| P=0.247N P=0.234 P=0.550 P=0.383N |P=0.324N P=0.429 P=0.325 P=0.409N | |COCH-ARM / FISHERS | P=0.293N P=0.345 P=0.579N P=0.421N |P=0.350N P=0.420 P=0.274 P=0.419N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 31/50 (62%) 33/50 (66%) 32/50 (64%) 26/50 (52%) |22/50 (44%) 22/50 (44%) 25/50 (50%) 25/50 (50%) | |POLY-3 ADJUSTED (b)| 62.4% 66.6% 64.0% 52.0% |44.4% 46.1% 51.1% 51.7% | |TERMINAL (d) | 23/41 (56%) 22/37 (60%) 22/40 (55%) 20/43 (47%) |10/37 (27%) 15/39 (39%) 17/40 (43%) 15/36 (42%) | |FIRST INCIDENCE | 556 446 497 281 |484 490 461 445 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.112N P=0.263 P=0.448 P=0.198N |P=0.276 P=0.510N P=0.491 P=0.365 | |POLY 3 | P=0.119N P=0.410 P=0.517 P=0.200N |P=0.244 P=0.515 P=0.324 P=0.303 | |POLY 1.5 | P=0.124N P=0.414 P=0.509 P=0.204N |P=0.253 P=0.536 P=0.320 P=0.320 | |POLY 6 | P=0.111N P=0.403 P=0.528 P=0.192N |P=0.231 P=0.500 P=0.331 P=0.285 | |LOGISTIC REGRESSION| P=0.184N P=0.509 P=0.527 P=0.252N |P=0.257 P=0.576 P=0.298 P=0.308 | |COCH-ARM / FISHERS | P=0.130N P=0.418 P=0.500 P=0.210N |P=0.267 P=0.580N P=0.344 P=0.344 | |=================================================================================================================================| Date: 12/02/98 EXPERIMENT: 05211 TEST: 06 Page 16 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 160 312 625 |0 312 625 1250 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 43/50 (86%) 46/50 (92%) 43/50 (86%) 37/50 (74%) |34/50 (68%) 33/50 (66%) 43/50 (86%) 37/50 (74%) | |POLY-3 ADJUSTED (b)| 86.0% 92.7% 86.0% 74.0% |68.0% 69.1% 87.8% 76.2% | |TERMINAL (d) | 34/41 (83%) 34/37 (92%) 33/40 (83%) 31/43 (72%) |21/37 (57%) 26/39 (67%) 35/40 (88%) 26/36 (72%) | |FIRST INCIDENCE | 556 446 497 281 |484 490 461 445 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.036N* P=0.129 P=0.492 P=0.115N |P=0.192 P=0.409N P=0.204 P=0.352 | |POLY 3 | P=0.023N* P=0.225 P=0.612 P=0.106N |P=0.123 P=0.539 P=0.015 * P=0.248 | |POLY 1.5 | P=0.024N* P=0.242 P=0.612 P=0.106N |P=0.139 P=0.584 P=0.015 * P=0.279 | |POLY 6 | P=0.022N* P=0.203 P=0.612 P=0.106N |P=0.106 P=0.499 P=0.014 * P=0.217 | |LOGISTIC REGRESSION| P=0.035N* P=0.291 (e) P=0.129N |P=0.174 P=0.500N P=0.029 * P=0.317 | |COCH-ARM / FISHERS | P=0.026N* P=0.262 P=0.613N P=0.105N |P=0.171 P=0.500N P=0.028 * P=0.330 | |=================================================================================================================================| (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).