TDMS Study 93020-07 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst DIISOPROPYLCARBODIIMIDE DATE: 01/03/05 EXPERIMENT: 93020 TEST: 07 TIME: 09:20:08 TEST TYPE: CHRONIC PAGE: 1 CONT: N01-ES 05451 ROUTE: SKIN APPLICATION NTP C#: 93020D PATHOLOGIST: HEATH, JAMES CAS: 693-13-0 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: 25022 Accidently Killed 25018 Dosing Accident 25023 Missing 25019 Moribund Sacrifice 25020 Natural Death 25017 Scheduled Sacrifice 25021 Terminal Sacrifice 25007 Wrong Sex REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst DIISOPROPYLCARBODIIMIDE DATE: 01/03/05 EXPERIMENT: 93020 TEST: 07 TIME: 09:20:08 TEST TYPE: CHRONIC CONT: N01-ES 05451 ROUTE: SKIN APPLICATION NTP C#: 93020D PATHOLOGIST: HEATH, JAMES CAS: 693-13-0 Rats(FISCHER 344) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Kidney Liver Lung Nose Pancreas Parathyroid Gland Pituitary Gland Prostate Salivary Glands Testes Thymus Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst DIISOPROPYLCARBODIIMIDE DATE: 01/03/05 EXPERIMENT: 93020 TEST: 07 TIME: 09:20:08 TEST TYPE: CHRONIC CONT: N01-ES 05451 ROUTE: SKIN APPLICATION NTP C#: 93020D PATHOLOGIST: HEATH, JAMES CAS: 693-13-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF DIISOPROPYLCARBODIIMIDE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Pheochromocytoma Benign Pheochromocytoma: Benign, Complex, Malignant, NOS Bone Osteosarcoma or Osteoma Clitoral/Preputial Gland Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Carcinoma Carcinoma or Adenoma Pituitary Gland: Pars Intermedia Carcinoma or Adenoma Testes Adenoma Thyroid Gland: C-Cell Carcinoma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Osteosarcoma or Osteoma Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Adenoma Islets, Pancreatic Adenoma Carcinoma or Adenoma Liver Hepatocellular Adenoma Mammary Gland Carcinoma Fibroadenoma Fibroma, Fibroadenoma or Adenoma Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma Skin Fibroma Schwannoma Malignant Thyroid Gland: C-Cell Carcinoma or Adenoma Uterus Carcinoma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Malignant and Benign Tumors =============================================================== Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 1 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 0/50 (0%) 0/50 (0%) 1/49 (2%) | |POLY-3 RATE (b) | 0/40.18 0/40.75 0/44.41 0/28.31 |3/41.69 0/42.03 0/43.75 1/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |7.2% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |2/30 (7%) 0/32 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | --- --- --- --- |710 --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.285N P=0.110N P=0.112N P=0.372N | |POLY 3 | (e) (e) (e) (e) |P=0.248N P=0.117N P=0.110N P=0.310N | |POLY 1.5 | (e) (e) (e) (e) |P=0.248N P=0.118N P=0.113N P=0.308N | |POLY 6 | (e) (e) (e) (e) |P=0.248N P=0.114N P=0.108N P=0.319N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.264N P=0.111N P=0.106N P=0.339N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.251N P=0.121N P=0.121N P=0.316N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.038N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/48 (4%) 8/50 (16%) 7/50 (14%) |0/49 (0%) 1/50 (2%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 3/40.23 2/39.75 8/44.41 7/28.90 |0/40.61 1/42.03 1/43.75 1/41.08 | |POLY-3 PERCENT (g) | 7.5% 5.0% 18.0% 24.2% |0.0% 2.4% 2.3% 2.4% | |TERMINAL (d) | 2/20 (10%) 2/29 (7%) 8/32 (25%) 4/17 (24%) |0/29 (0%) 1/32 (3%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | 716 729 (T) 729 (T) 630 |--- 729 (T) 729 (T) 725 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.012 * P=0.337N P=0.307 P=0.089 |P=0.338 P=0.520 P=0.520 P=0.471 | |POLY 3 | P=0.012 * P=0.506N P=0.130 P=0.055 |P=0.387 P=0.507 P=0.515 P=0.502 | |POLY 1.5 | P=0.016 * P=0.513N P=0.115 P=0.070 |P=0.389 P=0.505 P=0.512 P=0.503 | |POLY 6 | P=0.013 * P=0.489N P=0.157 P=0.056 |P=0.378 P=0.510 P=0.518 P=0.498 | |LOGISTIC REGRESSION| P=0.009 ** P=0.393N P=0.269 P=0.052 |P=0.346 P=0.520 P=0.520 P=0.485 | |COCH-ARM / FISHERS | P=0.059 P=0.520N P=0.100 P=0.159 |P=0.382 P=0.505 P=0.505 P=0.500 | |ORDER RESTRICTED | P=0.027 * (e) (e) (e) |P=0.329 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 2 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/48 (8%) 4/50 (8%) 2/50 (4%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) | |POLY-3 RATE (b) | 4/40.50 4/39.75 4/45.23 2/28.31 |0/40.61 0/42.03 0/43.75 1/41.08 | |POLY-3 PERCENT (g) | 9.9% 10.1% 8.8% 7.1% |0.0% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/20 (0%) 4/29 (14%) 2/32 (6%) 2/17 (12%) |0/29 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 688 729 (T) 563 729 (T) |--- --- --- 725 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.365N P=0.461N P=0.459N P=0.459N |P=0.172 (e) (e) P=0.471 | |POLY 3 | P=0.396N P=0.634 P=0.582N P=0.511N |P=0.198 (e) (e) P=0.502 | |POLY 1.5 | P=0.376N P=0.627 P=0.610N P=0.473N |P=0.199 (e) (e) P=0.503 | |POLY 6 | P=0.384N P=0.641N P=0.539N P=0.516N |P=0.195 (e) (e) P=0.498 | |LOGISTIC REGRESSION| P=0.399N P=0.591N P=0.629N P=0.491N |P=0.181 (e) (e) P=0.485 | |COCH-ARM / FISHERS | P=0.250N P=0.619 P=0.643N P=0.339N |P=0.197 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.554N (e) (e) (e) |P=0.122 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 6/48 (13%) 12/50 (24%) 9/50 (18%) |0/49 (0%) 1/50 (2%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 6/40.50 6/39.75 12/45.23 9/28.90 |0/40.61 1/42.03 1/43.75 1/41.08 | |POLY-3 PERCENT (g) | 14.8% 15.1% 26.5% 31.1% |0.0% 2.4% 2.3% 2.4% | |TERMINAL (d) | 2/20 (10%) 6/29 (21%) 10/32 (31%) 6/17 (35%) |0/29 (0%) 1/32 (3%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | 688 729 (T) 563 630 |--- 729 (T) 729 (T) 725 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049 * P=0.378N P=0.357 P=0.155 |P=0.338 P=0.520 P=0.520 P=0.471 | |POLY 3 | P=0.038 * P=0.609 P=0.142 P=0.093 |P=0.387 P=0.507 P=0.515 P=0.502 | |POLY 1.5 | P=0.052 P=0.599 P=0.119 P=0.123 |P=0.389 P=0.505 P=0.512 P=0.503 | |POLY 6 | P=0.040 * P=0.618N P=0.182 P=0.091 |P=0.378 P=0.510 P=0.518 P=0.498 | |LOGISTIC REGRESSION| P=0.034 * P=0.525N P=0.182 P=0.090 |P=0.346 P=0.520 P=0.520 P=0.485 | |COCH-ARM / FISHERS | P=0.184 P=0.591 P=0.096 P=0.288 |P=0.382 P=0.505 P=0.505 P=0.500 | |ORDER RESTRICTED | P=0.095 (e) (e) (e) |P=0.329 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 3 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Bone | | Osteosarcoma or Osteoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 0/44.41 2/28.51 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 1/17 (6%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- 676 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020 * (e) (e) P=0.180 |(e) (e) (e) (e) | |POLY 3 | P=0.038 * (e) (e) P=0.170 |(e) (e) (e) (e) | |POLY 1.5 | P=0.038 * (e) (e) P=0.182 |(e) (e) (e) (e) | |POLY 6 | P=0.039 * (e) (e) P=0.171 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.022 * (e) (e) P=0.165 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Brain | | Glioma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 0/44.41 0/28.31 |0/41.61 0/42.03 2/44.49 1/41.82 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 4.5% 2.4% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.235 (e) P=0.254 P=0.508 | |POLY 3 | (e) (e) (e) (e) |P=0.248 (e) P=0.252 P=0.501 | |POLY 1.5 | (e) (e) (e) (e) |P=0.249 (e) P=0.248 P=0.501 | |POLY 6 | (e) (e) (e) (e) |P=0.239 (e) P=0.257 P=0.498 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.152 (e) P=0.182 P=0.315 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.241 (e) P=0.247 P=0.495 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.180 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 4 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 1/40.18 0/41.64 0/44.41 0/28.31 |0/41.61 0/42.03 2/44.49 1/41.82 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% |0.0% 0.0% 4.5% 2.4% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |--- --- 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.311N P=0.419N P=0.406N P=0.532N |P=0.235 (e) P=0.254 P=0.508 | |POLY 3 | P=0.240N P=0.493N P=0.480N P=0.568N |P=0.248 (e) P=0.252 P=0.501 | |POLY 1.5 | P=0.260N P=0.497N P=0.489N P=0.554N |P=0.249 (e) P=0.248 P=0.501 | |POLY 6 | P=0.233N P=0.485N P=0.466N P=0.568N |P=0.239 (e) P=0.257 P=0.498 | |LOGISTIC REGRESSION| P=0.311N (e) (e) (e) |P=0.152 (e) P=0.182 P=0.315 | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.241 (e) P=0.247 P=0.495 | |ORDER RESTRICTED | P=0.193N (e) (e) (e) |P=0.180 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 4/50 (8%) |2/50 (4%) 3/49 (6%) 5/50 (10%) 2/49 (4%) | |POLY-3 RATE (b) | 1/40.18 1/41.64 1/44.41 4/29.07 |2/41.61 3/41.03 5/44.17 2/41.28 | |POLY-3 PERCENT (g) | 2.5% 2.4% 2.3% 13.8% |4.8% 7.3% 11.3% 4.8% | |TERMINAL (d) | 1/20 (5%) 1/30 (3%) 1/32 (3%) 2/17 (12%) |2/30 (7%) 3/31 (10%) 4/32 (13%) 1/25 (4%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 607 |729 (T) 729 (T) 606 673 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.026 * P=0.669N P=0.654N P=0.118 |P=0.497 P=0.515 P=0.241 P=0.636 | |POLY 3 | P=0.046 * P=0.753N P=0.738N P=0.097 |P=0.578N P=0.494 P=0.240 P=0.692 | |POLY 1.5 | P=0.047 * P=0.757N P=0.749N P=0.110 |P=0.575N P=0.491 P=0.233 P=0.693 | |POLY 6 | P=0.048 * P=0.744N P=0.721N P=0.100 |P=0.567 P=0.499 P=0.248 P=0.686 | |LOGISTIC REGRESSION| P=0.026 * P=0.669N P=0.654N P=0.094 |P=0.566 P=0.515 P=0.239 P=0.679 | |COCH-ARM / FISHERS | P=0.067 P=0.753N P=0.753N P=0.181 |P=0.573 P=0.490 P=0.218 P=0.684 | |ORDER RESTRICTED | P=0.025 * (e) (e) (e) |P=0.438 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 5 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 6/49 (12%) 1/50 (2%) 2/49 (4%) | |POLY-3 RATE (b) | 1/40.24 2/42.08 0/44.41 0/28.31 |2/42.17 6/41.68 1/43.75 2/41.07 | |POLY-3 PERCENT (g) | 2.5% 4.8% 0.0% 0.0% |4.7% 14.4% 2.3% 4.9% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |1/30 (3%) 4/31 (13%) 1/32 (3%) 2/25 (8%) | |FIRST INCIDENCE | 714 621 --- --- |556 513 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215N P=0.573 P=0.428N P=0.560N |P=0.382N P=0.150 P=0.482N P=0.648 | |POLY 3 | P=0.195N P=0.516 P=0.480N P=0.568N |P=0.321N P=0.127 P=0.487N P=0.685 | |POLY 1.5 | P=0.201N P=0.507 P=0.489N P=0.554N |P=0.317N P=0.127 P=0.490N P=0.689 | |POLY 6 | P=0.183N P=0.532 P=0.467N P=0.569N |P=0.331N P=0.130 P=0.485N P=0.674 | |LOGISTIC REGRESSION| P=0.217N P=0.505 P=0.457N P=0.565N |P=0.319N P=0.128 P=0.507N P=0.691 | |COCH-ARM / FISHERS | P=0.188N P=0.500 P=0.500N P=0.500N |P=0.324N P=0.128 P=0.500N P=0.684 | |ORDER RESTRICTED | P=0.258N (e) (e) (e) |P=0.209N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 1/50 (2%) 4/50 (8%) |4/50 (8%) 9/49 (18%) 6/50 (12%) 4/49 (8%) | |POLY-3 RATE (b) | 2/40.24 3/42.08 1/44.41 4/29.07 |4/42.17 9/41.68 6/44.17 4/41.28 | |POLY-3 PERCENT (g) | 5.0% 7.1% 2.3% 13.8% |9.5% 21.6% 13.6% 9.7% | |TERMINAL (d) | 1/20 (5%) 1/30 (3%) 1/32 (3%) 2/17 (12%) |3/30 (10%) 7/31 (23%) 5/32 (16%) 3/25 (12%) | |FIRST INCIDENCE | 714 621 729 (T) 607 |556 513 606 673 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.176 P=0.628 P=0.352N P=0.234 |P=0.478N P=0.132 P=0.406 P=0.563 | |POLY 3 | P=0.220 P=0.520 P=0.466N P=0.203 |P=0.373N P=0.107 P=0.398 P=0.632 | |POLY 1.5 | P=0.224 P=0.510 P=0.481N P=0.225 |P=0.366N P=0.107 P=0.390 P=0.637 | |POLY 6 | P=0.232 P=0.542 P=0.442N P=0.207 |P=0.393N P=0.110 P=0.406 P=0.619 | |LOGISTIC REGRESSION| P=0.167 P=0.527 P=0.385N P=0.195 |P=0.372N P=0.110 P=0.393 P=0.635 | |COCH-ARM / FISHERS | P=0.292 P=0.500 P=0.500N P=0.339 |P=0.378N P=0.109 P=0.370 P=0.631 | |ORDER RESTRICTED | P=0.126 (e) (e) (e) |P=0.350N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 6 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 12/50 (24%) 10/50 (20%) 5/50 (10%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 5/41.01 12/42.04 10/45.45 5/29.34 |0/41.61 0/42.03 0/43.75 2/41.51 | |POLY-3 PERCENT (g) | 12.2% 28.6% 22.0% 17.0% |0.0% 0.0% 0.0% 4.8% | |TERMINAL (d) | 2/20 (10%) 11/30 (37%) 6/32 (19%) 3/17 (18%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | 608 617 563 513 |--- --- --- 601 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.552 P=0.183 P=0.359 P=0.461 |P=0.039 * (e) (e) P=0.217 | |POLY 3 | P=0.414 P=0.054 P=0.178 P=0.412 |P=0.044 * (e) (e) P=0.236 | |POLY 1.5 | P=0.468 P=0.053 P=0.155 P=0.455 |P=0.045 * (e) (e) P=0.237 | |POLY 6 | P=0.435 P=0.058 P=0.217 P=0.413 |P=0.043 * (e) (e) P=0.232 | |LOGISTIC REGRESSION| P=0.483 P=0.073 P=0.156 P=0.439 |P=0.043 * (e) (e) P=0.229 | |COCH-ARM / FISHERS | P=0.348N P=0.054 P=0.131 P=0.630N |P=0.045 * (e) (e) P=0.242 | |ORDER RESTRICTED | P=0.236 (e) (e) (e) |P=0.029 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/40.18 1/41.64 1/44.41 0/28.31 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 5.0% 2.4% 2.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/20 (10%) 1/30 (3%) 1/32 (3%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.158N P=0.359N P=0.338N P=0.273N |(e) (e) (e) (e) | |POLY 3 | P=0.184N P=0.487N P=0.465N P=0.322N |(e) (e) (e) (e) | |POLY 1.5 | P=0.182N P=0.494N P=0.481N P=0.304N |(e) (e) (e) (e) | |POLY 6 | P=0.179N P=0.474N P=0.441N P=0.322N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.158N P=0.359N P=0.338N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.153N P=0.500N P=0.500N P=0.247N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.191N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 7 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 13/50 (26%) 11/50 (22%) 5/50 (10%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 7/41.01 13/42.04 11/45.45 5/29.34 |0/41.61 0/42.03 0/43.75 2/41.51 | |POLY-3 PERCENT (g) | 17.1% 30.9% 24.2% 17.0% |0.0% 0.0% 0.0% 4.8% | |TERMINAL (d) | 4/20 (20%) 12/30 (40%) 7/32 (22%) 3/17 (18%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | 608 617 563 513 |--- --- --- 601 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.365N P=0.327 P=0.537 P=0.556N |P=0.039 * (e) (e) P=0.217 | |POLY 3 | P=0.484N P=0.107 P=0.291 P=0.622N |P=0.044 * (e) (e) P=0.236 | |POLY 1.5 | P=0.436N P=0.105 P=0.256 P=0.575N |P=0.045 * (e) (e) P=0.237 | |POLY 6 | P=0.457N P=0.116 P=0.347 P=0.621N |P=0.043 * (e) (e) P=0.232 | |LOGISTIC REGRESSION| P=0.449N P=0.146 P=0.286 P=0.613N |P=0.043 * (e) (e) P=0.229 | |COCH-ARM / FISHERS | P=0.192N P=0.105 P=0.218 P=0.380N |P=0.045 * (e) (e) P=0.242 | |ORDER RESTRICTED | P=0.380 (e) (e) (e) |P=0.029 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |6/50 (12%) 1/50 (2%) 2/50 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 0/40.18 2/41.83 1/44.41 0/28.31 |6/42.04 1/42.03 2/43.75 1/41.07 | |POLY-3 PERCENT (g) | 0.0% 4.8% 2.3% 0.0% |14.3% 2.4% 4.6% 2.4% | |TERMINAL (d) | 0/20 (0%) 1/30 (3%) 1/32 (3%) 0/17 (0%) |4/30 (13%) 1/32 (3%) 2/32 (6%) 1/25 (4%) | |FIRST INCIDENCE | --- 682 729 (T) --- |632 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.526N P=0.295 P=0.594 (e) |P=0.067N P=0.052N P=0.117N P=0.090N | |POLY 3 | P=0.550N P=0.246 P=0.520 (e) |P=0.049N* P=0.055N P=0.119N P=0.058N | |POLY 1.5 | P=0.539N P=0.241 P=0.511 (e) |P=0.048N* P=0.056N P=0.123N P=0.057N | |POLY 6 | P=0.538N P=0.256 P=0.534 (e) |P=0.051N P=0.053N P=0.117N P=0.063N | |LOGISTIC REGRESSION| P=0.542N P=0.253 P=0.594 (e) |P=0.052N P=0.054N P=0.114N P=0.063N | |COCH-ARM / FISHERS | P=0.461N P=0.247 P=0.500 (e) |P=0.052N P=0.056N P=0.134N P=0.059N | |ORDER RESTRICTED | P=0.381 (e) (e) (e) |P=0.014N* (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 8 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 1/40.24 2/41.64 0/44.41 0/28.31 |0/41.61 1/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 2.5% 4.8% 0.0% 0.0% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 2/30 (7%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 1/32 (3%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 714 729 (T) --- --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.202N P=0.627 P=0.428N P=0.560N |P=0.599N P=0.513 (e) (e) | |POLY 3 | P=0.196N P=0.512 P=0.480N P=0.568N |P=0.566N P=0.502 (e) (e) | |POLY 1.5 | P=0.202N P=0.506 P=0.489N P=0.554N |P=0.567N P=0.501 (e) (e) | |POLY 6 | P=0.183N P=0.525 P=0.467N P=0.569N |P=0.563N P=0.505 (e) (e) | |LOGISTIC REGRESSION| P=0.212N P=0.578 P=0.457N P=0.565N |(e) P=0.513 (e) (e) | |COCH-ARM / FISHERS | P=0.188N P=0.500 P=0.500N P=0.500N |P=0.571N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.256N (e) (e) (e) |P=0.385N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |4/50 (8%) 0/50 (0%) 2/50 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 1/44.72 0/28.31 |4/41.69 0/42.03 2/43.91 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |9.6% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |3/30 (10%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 645 --- |710 --- 686 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.670 (e) P=0.550 (e) |P=0.074N P=0.056N P=0.305N P=0.089N | |POLY 3 | P=0.495 (e) P=0.521 (e) |P=0.060N P=0.059N P=0.313N P=0.061N | |POLY 1.5 | P=0.546 (e) P=0.511 (e) |P=0.060N P=0.060N P=0.320N P=0.061N | |POLY 6 | P=0.479 (e) P=0.536 (e) |P=0.063N P=0.057N P=0.305N P=0.064N | |LOGISTIC REGRESSION| P=0.709 (e) P=0.468 (e) |P=0.063N P=0.055N P=0.304N P=0.074N | |COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.063N P=0.059N P=0.339N P=0.061N | |ORDER RESTRICTED | P=0.416 (e) (e) (e) |P=0.012N* (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 9 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |4/50 (8%) 1/50 (2%) 2/50 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 1/44.72 0/28.31 |4/41.69 1/42.23 2/43.91 1/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |9.6% 2.4% 4.6% 2.4% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |3/30 (10%) 0/32 (0%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | --- --- 645 --- |710 677 686 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.670 (e) P=0.550 (e) |P=0.201N P=0.162N P=0.305N P=0.238N | |POLY 3 | P=0.495 (e) P=0.521 (e) |P=0.167N P=0.174N P=0.313N P=0.182N | |POLY 1.5 | P=0.546 (e) P=0.511 (e) |P=0.166N P=0.177N P=0.320N P=0.180N | |POLY 6 | P=0.479 (e) P=0.536 (e) |P=0.173N P=0.168N P=0.305N P=0.189N | |LOGISTIC REGRESSION| P=0.709 (e) P=0.468 (e) |P=0.170N P=0.171N P=0.304N P=0.209N | |COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.169N P=0.181N P=0.339N P=0.187N | |ORDER RESTRICTED | P=0.416 (e) (e) (e) |P=0.098N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 1/50 (2%) 1/50 (2%) |12/50 (24%) 11/50 (22%) 21/50 (42%) 16/49 (33%) | |POLY-3 RATE (b) | 0/40.18 4/41.83 1/44.41 1/28.31 |12/42.74 11/42.03 21/45.13 16/42.85 | |POLY-3 PERCENT (g) | 0.0% 9.6% 2.3% 3.5% |28.1% 26.2% 46.5% 37.3% | |TERMINAL (d) | 0/20 (0%) 3/30 (10%) 1/32 (3%) 1/17 (6%) |8/30 (27%) 10/32 (31%) 17/32 (53%) 9/25 (36%) | |FIRST INCIDENCE | --- 682 729 (T) 729 (T) |606 728 465 559 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.597 P=0.113 P=0.594 P=0.468 |P=0.044 * P=0.441N P=0.073 P=0.154 | |POLY 3 | P=0.509 P=0.065 P=0.520 P=0.432 |P=0.124 P=0.519N P=0.055 P=0.245 | |POLY 1.5 | P=0.534 P=0.062 P=0.511 P=0.446 |P=0.125 P=0.512N P=0.052 P=0.248 | |POLY 6 | P=0.523 P=0.070 P=0.534 P=0.432 |P=0.113 P=0.526N P=0.055 P=0.231 | |LOGISTIC REGRESSION| P=0.572 P=0.078 P=0.594 P=0.468 |P=0.106 P=0.475N P=0.059 P=0.235 | |COCH-ARM / FISHERS | P=0.556N P=0.059 P=0.500 P=0.500 |P=0.111 P=0.500N P=0.044 * P=0.232 | |ORDER RESTRICTED | P=0.245 (e) (e) (e) |P=0.106 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 10 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 1/50 (2%) 1/50 (2%) |12/50 (24%) 12/50 (24%) 21/50 (42%) 16/49 (33%) | |POLY-3 RATE (b) | 0/40.18 4/41.83 1/44.41 1/28.31 |12/42.74 12/42.23 21/45.13 16/42.85 | |POLY-3 PERCENT (g) | 0.0% 9.6% 2.3% 3.5% |28.1% 28.4% 46.5% 37.3% | |TERMINAL (d) | 0/20 (0%) 3/30 (10%) 1/32 (3%) 1/17 (6%) |8/30 (27%) 10/32 (31%) 17/32 (53%) 9/25 (36%) | |FIRST INCIDENCE | --- 682 729 (T) 729 (T) |606 677 465 559 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.597 P=0.113 P=0.594 P=0.468 |P=0.053 P=0.530N P=0.073 P=0.154 | |POLY 3 | P=0.509 P=0.065 P=0.520 P=0.432 |P=0.142 P=0.582 P=0.055 P=0.245 | |POLY 1.5 | P=0.534 P=0.062 P=0.511 P=0.446 |P=0.143 P=0.585 P=0.052 P=0.248 | |POLY 6 | P=0.523 P=0.070 P=0.534 P=0.432 |P=0.129 P=0.581 P=0.055 P=0.231 | |LOGISTIC REGRESSION| P=0.572 P=0.078 P=0.594 P=0.468 |P=0.123 P=0.573N P=0.059 P=0.235 | |COCH-ARM / FISHERS | P=0.556N P=0.059 P=0.500 P=0.500 |P=0.127 P=0.592N P=0.044 * P=0.232 | |ORDER RESTRICTED | P=0.245 (e) (e) (e) |P=0.131 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 2/50 (4%) 1/50 (2%) |14/50 (28%) 12/50 (24%) 22/50 (44%) 16/49 (33%) | |POLY-3 RATE (b) | 0/40.18 4/41.83 2/44.72 1/28.31 |14/42.81 12/42.23 22/45.29 16/42.85 | |POLY-3 PERCENT (g) | 0.0% 9.6% 4.5% 3.5% |32.7% 28.4% 48.6% 37.3% | |TERMINAL (d) | 0/20 (0%) 3/30 (10%) 1/32 (3%) 1/17 (6%) |9/30 (30%) 10/32 (31%) 17/32 (53%) 9/25 (36%) | |FIRST INCIDENCE | --- 682 645 729 (T) |606 677 465 559 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.541 P=0.113 P=0.321 P=0.468 |P=0.103 P=0.350N P=0.123 P=0.268 | |POLY 3 | P=0.432 P=0.065 P=0.262 P=0.432 |P=0.239 P=0.423N P=0.093 P=0.411 | |POLY 1.5 | P=0.466 P=0.062 P=0.250 P=0.446 |P=0.240 P=0.418N P=0.087 P=0.413 | |POLY 6 | P=0.443 P=0.070 P=0.280 P=0.432 |P=0.222 P=0.427N P=0.096 P=0.393 | |LOGISTIC REGRESSION| P=0.509 P=0.078 P=0.239 P=0.468 |P=0.211 P=0.383N P=0.095 P=0.393 | |COCH-ARM / FISHERS | P=0.577N P=0.059 P=0.247 P=0.500 |P=0.213 P=0.410N P=0.072 P=0.388 | |ORDER RESTRICTED | P=0.214 (e) (e) (e) |P=0.172 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 11 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Papilloma Squamous or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 1/44.41 0/28.31 |2/41.61 0/42.03 1/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.8% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 1/32 (3%) 0/17 (0%) |2/30 (7%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |729 (T) --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.689 (e) P=0.594 (e) |P=0.212N P=0.224N P=0.477N P=0.279N | |POLY 3 | P=0.496 (e) P=0.520 (e) |P=0.190N P=0.235N P=0.483N P=0.240N | |POLY 1.5 | P=0.547 (e) P=0.511 (e) |P=0.189N P=0.236N P=0.488N P=0.238N | |POLY 6 | P=0.481 (e) P=0.534 (e) |P=0.193N P=0.231N P=0.478N P=0.245N | |LOGISTIC REGRESSION| (e) (e) P=0.594 (e) |P=0.212N (e) P=0.477N (e) | |COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.191N P=0.247N P=0.500N P=0.253N | |ORDER RESTRICTED | P=0.415 (e) (e) (e) |P=0.076N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 2/44.85 0/28.31 |1/42.46 0/42.03 1/43.90 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 0.0% |2.4% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 645 --- |394 --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537 (e) P=0.302 (e) |P=0.406N P=0.504N P=0.745N P=0.496N | |POLY 3 | P=0.357 (e) P=0.262 (e) |P=0.409N P=0.502N P=0.753N P=0.507N | |POLY 1.5 | P=0.413 (e) P=0.251 (e) |P=0.407N P=0.502N P=0.755N P=0.504N | |POLY 6 | P=0.341 (e) P=0.281 (e) |P=0.414N P=0.500N P=0.751N P=0.512N | |LOGISTIC REGRESSION| P=0.564 (e) P=0.220 (e) |P=0.498N P=0.487N P=0.681 P=0.783N | |COCH-ARM / FISHERS | P=0.595 (e) P=0.247 (e) |P=0.409N P=0.500N P=0.753N P=0.505N | |ORDER RESTRICTED | P=0.290 (e) (e) (e) |P=0.257N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 12 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |3/50 (6%) 0/50 (0%) 2/50 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 3/44.85 0/28.31 |3/42.46 0/42.03 2/43.90 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 0.0% |7.1% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 1/32 (3%) 0/17 (0%) |2/30 (7%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 645 --- |394 --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.467 (e) P=0.190 (e) |P=0.141N P=0.116N P=0.470N P=0.143N | |POLY 3 | P=0.275 (e) P=0.139 (e) |P=0.127N P=0.120N P=0.485N P=0.124N | |POLY 1.5 | P=0.333 (e) P=0.130 (e) |P=0.125N P=0.120N P=0.489N P=0.122N | |POLY 6 | P=0.260 (e) P=0.156 (e) |P=0.131N P=0.118N P=0.479N P=0.129N | |LOGISTIC REGRESSION| P=0.467 (e) P=0.123 (e) |P=0.135N P=0.119N P=0.528N P=0.140N | |COCH-ARM / FISHERS | P=0.539 (e) P=0.121 (e) |P=0.128N P=0.121N P=0.500N P=0.125N | |ORDER RESTRICTED | P=0.206 (e) (e) (e) |P=0.039N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Oral Mucosa | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 2/44.85 0/28.31 |1/42.46 0/42.03 1/43.90 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 0.0% |2.4% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 645 --- |394 --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537 (e) P=0.302 (e) |P=0.406N P=0.504N P=0.745N P=0.496N | |POLY 3 | P=0.357 (e) P=0.262 (e) |P=0.409N P=0.502N P=0.753N P=0.507N | |POLY 1.5 | P=0.413 (e) P=0.251 (e) |P=0.407N P=0.502N P=0.755N P=0.504N | |POLY 6 | P=0.341 (e) P=0.281 (e) |P=0.414N P=0.500N P=0.751N P=0.512N | |LOGISTIC REGRESSION| P=0.564 (e) P=0.220 (e) |P=0.498N P=0.487N P=0.681 P=0.783N | |COCH-ARM / FISHERS | P=0.595 (e) P=0.247 (e) |P=0.409N P=0.500N P=0.753N P=0.505N | |ORDER RESTRICTED | P=0.290 (e) (e) (e) |P=0.257N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 13 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pancreas | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 3/40.18 1/41.64 2/44.95 0/28.31 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 7.5% 2.4% 4.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/20 (15%) 1/30 (3%) 1/32 (3%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 563 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.117N P=0.172N P=0.327N P=0.148N |(e) (e) (e) (e) | |POLY 3 | P=0.150N P=0.292N P=0.449N P=0.194N |(e) (e) (e) (e) | |POLY 1.5 | P=0.144N P=0.299N P=0.472N P=0.176N |(e) (e) (e) (e) | |POLY 6 | P=0.147N P=0.277N P=0.414N P=0.193N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.142N P=0.172N P=0.465N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.104N P=0.309N P=0.500N P=0.121N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.115N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 33/50 (66%) 42/50 (84%) 20/50 (40%) |33/50 (66%) 34/50 (68%) 33/50 (66%) 27/49 (55%) | |POLY-3 RATE (b) | 29/45.46 33/47.21 42/49.46 20/31.56 |33/44.47 34/46.41 33/47.67 27/43.85 | |POLY-3 PERCENT (g) | 63.8% 69.9% 84.9% 63.4% |74.2% 73.3% 69.2% 61.6% | |TERMINAL (d) | 14/20 (70%) 19/30 (63%) 27/32 (84%) 12/17 (71%) |24/30 (80%) 22/32 (69%) 22/32 (69%) 17/25 (68%) | |FIRST INCIDENCE | 522 444 444 290 |437 522 465 469 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.435N P=0.355N P=0.498 P=0.370N |P=0.383N P=0.522N P=0.419N P=0.443N | |POLY 3 | P=0.262 P=0.338 P=0.011 * P=0.582N |P=0.090N P=0.555N P=0.379N P=0.135N | |POLY 1.5 | P=0.475 P=0.301 P=0.006 ** P=0.402N |P=0.086N P=0.569 P=0.449N P=0.139N | |POLY 6 | P=0.229 P=0.416 P=0.026 * P=0.572 |P=0.117N P=0.454N P=0.309N P=0.148N | |LOGISTIC REGRESSION| P=0.441N P=0.274 P=0.005 ** P=0.467N |P=0.088N P=0.506 P=0.487N P=0.147N | |COCH-ARM / FISHERS | P=0.031N* P=0.268 P=0.004 ** P=0.055N |P=0.119N P=0.500 P=0.583N P=0.183N | |ORDER RESTRICTED | P=0.186 (e) (e) (e) |P=0.146N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 14 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |3/50 (6%) 1/50 (2%) 1/50 (2%) 4/49 (8%) | |POLY-3 RATE (b) | 5/41.63 1/42.23 0/44.41 2/28.31 |3/42.21 1/42.10 1/43.75 4/42.10 | |POLY-3 PERCENT (g) | 12.0% 2.4% 0.0% 7.1% |7.1% 2.4% 2.3% 9.5% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 2/17 (12%) |1/30 (3%) 0/32 (0%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 463 542 --- 729 (T) |626 712 729 (T) 593 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.232N P=0.080N P=0.020N* P=0.347N |P=0.264 P=0.294N P=0.286N P=0.460 | |POLY 3 | P=0.143N P=0.097N P=0.025N* P=0.397N |P=0.300 P=0.306N P=0.292N P=0.498 | |POLY 1.5 | P=0.156N P=0.100N P=0.028N* P=0.353N |P=0.301 P=0.306N P=0.295N P=0.500 | |POLY 6 | P=0.133N P=0.090N P=0.021N* P=0.408N |P=0.294 P=0.304N P=0.291N P=0.490 | |LOGISTIC REGRESSION| P=0.149N P=0.105N P=0.049N* P=0.323N |P=0.292 P=0.304N P=0.299N P=0.480 | |COCH-ARM / FISHERS | P=0.165N P=0.102N P=0.028N* P=0.218N |P=0.293 P=0.309N P=0.309N P=0.489 | |ORDER RESTRICTED | P=0.079N (e) (e) (e) |P=0.198 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 34/50 (68%) 34/50 (68%) 42/50 (84%) 22/50 (44%) |36/50 (72%) 35/50 (70%) 34/50 (68%) 30/49 (61%) | |POLY-3 RATE (b) | 34/46.91 34/47.80 42/49.46 22/31.56 |36/45.07 35/46.48 34/47.67 30/44.75 | |POLY-3 PERCENT (g) | 72.5% 71.1% 84.9% 69.7% |79.9% 75.3% 71.3% 67.0% | |TERMINAL (d) | 15/20 (75%) 19/30 (63%) 27/32 (84%) 14/17 (82%) |25/30 (83%) 22/32 (69%) 23/32 (72%) 18/25 (72%) | |FIRST INCIDENCE | 463 444 444 290 |437 522 465 469 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.315N P=0.155N P=0.292N P=0.250N |P=0.432N P=0.383N P=0.284N P=0.462N | |POLY 3 | P=0.376 P=0.534N P=0.095 P=0.496N |P=0.090N P=0.389N P=0.229N P=0.113N | |POLY 1.5 | P=0.434N P=0.564N P=0.070 P=0.265N |P=0.090N P=0.446N P=0.282N P=0.122N | |POLY 6 | P=0.299 P=0.468N P=0.150 P=0.603N |P=0.114N P=0.308N P=0.189N P=0.123N | |LOGISTIC REGRESSION| P=0.252N P=0.573 P=0.042 * P=0.298N |P=0.099N P=0.496N P=0.309N P=0.134N | |COCH-ARM / FISHERS | P=0.008N** P=0.585N P=0.050 P=0.013N* |P=0.135N P=0.500N P=0.414N P=0.178N | |ORDER RESTRICTED | P=0.388 (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 15 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/41.05 0/41.64 0/44.41 0/28.31 |0/41.61 1/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 4.9% 0.0% 0.0% 0.0% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 1/32 (3%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 533 --- --- --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.136N P=0.242N P=0.222N P=0.333N |P=0.599N P=0.513 (e) (e) | |POLY 3 | P=0.086N P=0.234N P=0.220N P=0.328N |P=0.566N P=0.502 (e) (e) | |POLY 1.5 | P=0.095N P=0.236N P=0.228N P=0.307N |P=0.567N P=0.501 (e) (e) | |POLY 6 | P=0.081N P=0.228N P=0.208N P=0.332N |P=0.563N P=0.505 (e) (e) | |LOGISTIC REGRESSION| P=0.056N P=0.236N P=0.296N P=0.205N |(e) P=0.513 (e) (e) | |COCH-ARM / FISHERS | P=0.115N P=0.247N P=0.247N P=0.247N |P=0.571N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.078N (e) (e) (e) |P=0.385N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 3/41.05 0/41.64 0/44.41 0/28.31 |0/41.61 1/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 7.3% 0.0% 0.0% 0.0% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 1/32 (3%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 533 --- --- --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053N P=0.102N P=0.089N P=0.187N |P=0.599N P=0.513 (e) (e) | |POLY 3 | P=0.033N* P=0.115N P=0.105N P=0.199N |P=0.566N P=0.502 (e) (e) | |POLY 1.5 | P=0.038N* P=0.118N P=0.111N P=0.179N |P=0.567N P=0.501 (e) (e) | |POLY 6 | P=0.031N* P=0.111N P=0.096N P=0.203N |P=0.563N P=0.505 (e) (e) | |LOGISTIC REGRESSION| P=0.033N* P=0.124N P=0.150N P=0.139N |(e) P=0.513 (e) (e) | |COCH-ARM / FISHERS | P=0.047N* P=0.121N P=0.121N P=0.121N |P=0.571N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.030N* (e) (e) (e) |P=0.385N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 16 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Prostate | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | | |POLY-3 RATE (b) | 1/40.18 2/41.64 1/44.41 0/28.31 | | |POLY-3 PERCENT (g) | 2.5% 4.8% 2.3% 0.0% | | |TERMINAL (d) | 1/20 (5%) 2/30 (7%) 1/32 (3%) 0/17 (0%) | | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.272N P=0.641 P=0.654N P=0.532N | | |POLY 3 | P=0.312N P=0.513 P=0.738N P=0.568N | | |POLY 1.5 | P=0.305N P=0.506 P=0.749N P=0.554N | | |POLY 6 | P=0.301N P=0.526 P=0.721N P=0.568N | | |LOGISTIC REGRESSION| P=0.272N P=0.641 P=0.654N (e) | | |COCH-ARM / FISHERS | P=0.247N P=0.500 P=0.753N P=0.500N | | |ORDER RESTRICTED | P=0.311N (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |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) | 4/50 (8%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 4/40.64 2/41.64 4/44.41 1/28.31 |1/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 9.8% 4.8% 9.0% 3.5% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 2/30 (7%) 4/32 (13%) 1/17 (6%) |1/30 (3%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 662 729 (T) 729 (T) 729 (T) |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.249N P=0.224N P=0.421N P=0.272N |P=0.323N P=0.487N P=0.487N P=0.536N | |POLY 3 | P=0.314N P=0.325N P=0.594N P=0.307N |P=0.307N P=0.498N P=0.490N P=0.503N | |POLY 1.5 | P=0.291N P=0.332N P=0.617N P=0.276N |P=0.308N P=0.499N P=0.493N P=0.501N | |POLY 6 | P=0.313N P=0.312N P=0.561N P=0.311N |P=0.304N P=0.495N P=0.487N P=0.507N | |LOGISTIC REGRESSION| P=0.278N P=0.296N P=0.526N P=0.293N |P=0.323N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.186N P=0.339N P=0.643N P=0.181N |P=0.308N P=0.500N P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.285N (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 17 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 2/50 (4%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 3/49 (6%) | |POLY-3 RATE (b) | 5/40.89 4/41.83 2/44.41 3/29.23 |0/41.61 0/42.03 1/43.75 3/41.55 | |POLY-3 PERCENT (g) | 12.2% 9.6% 4.5% 10.3% |0.0% 0.0% 2.3% 7.2% | |TERMINAL (d) | 2/20 (10%) 3/30 (10%) 2/32 (6%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 608 682 729 (T) 606 |--- --- 729 (T) 662 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.367N P=0.342N P=0.102N P=0.511N |P=0.015 * (e) P=0.513 P=0.110 | |POLY 3 | P=0.330N P=0.486N P=0.183N P=0.549N |P=0.019 * (e) P=0.510 P=0.118 | |POLY 1.5 | P=0.328N P=0.494N P=0.198N P=0.511N |P=0.019 * (e) P=0.507 P=0.118 | |POLY 6 | P=0.315N P=0.468N P=0.162N P=0.543N |P=0.018 * (e) P=0.513 P=0.115 | |LOGISTIC REGRESSION| P=0.393N P=0.463N P=0.171N P=0.520N |P=0.019 * (e) P=0.513 P=0.118 | |COCH-ARM / FISHERS | P=0.256N P=0.500N P=0.218N P=0.357N |P=0.019 * (e) P=0.500 P=0.117 | |ORDER RESTRICTED | P=0.372N (e) (e) (e) |P=0.020 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 3/50 (6%) 3/50 (6%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 3/49 (6%) | |POLY-3 RATE (b) | 5/40.89 4/41.83 3/44.70 3/29.23 |0/41.61 2/42.13 1/43.75 3/41.55 | |POLY-3 PERCENT (g) | 12.2% 9.6% 6.7% 10.3% |0.0% 4.8% 2.3% 7.2% | |TERMINAL (d) | 2/20 (10%) 3/30 (10%) 2/32 (6%) 0/17 (0%) |0/30 (0%) 1/32 (3%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 608 682 649 606 |--- 703 729 (T) 662 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.404N P=0.342N P=0.195N P=0.511N |P=0.080 P=0.257 P=0.513 P=0.110 | |POLY 3 | P=0.382N P=0.486N P=0.308N P=0.549N |P=0.103 P=0.240 P=0.510 P=0.118 | |POLY 1.5 | P=0.374N P=0.494N P=0.330N P=0.511N |P=0.103 P=0.238 P=0.507 P=0.118 | |POLY 6 | P=0.366N P=0.468N P=0.276N P=0.543N |P=0.100 P=0.243 P=0.513 P=0.115 | |LOGISTIC REGRESSION| P=0.421N P=0.463N P=0.318N P=0.520N |P=0.099 P=0.243 P=0.513 P=0.118 | |COCH-ARM / FISHERS | P=0.278N P=0.500N P=0.357N P=0.357N |P=0.099 P=0.247 P=0.500 P=0.117 | |ORDER RESTRICTED | P=0.470N (e) (e) (e) |P=0.056 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 18 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 1/44.70 0/28.31 |0/41.61 2/42.13 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |0.0% 4.8% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 1/32 (3%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 649 --- |--- 703 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.667 (e) P=0.541 (e) |P=0.434N P=0.257 (e) (e) | |POLY 3 | P=0.495 (e) P=0.521 (e) |P=0.402N P=0.240 (e) (e) | |POLY 1.5 | P=0.546 (e) P=0.511 (e) |P=0.403N P=0.238 (e) (e) | |POLY 6 | P=0.479 (e) P=0.536 (e) |P=0.402N P=0.243 (e) (e) | |LOGISTIC REGRESSION| P=0.704 (e) P=0.470 (e) |P=0.413N P=0.243 (e) (e) | |COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.409N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.416 (e) (e) (e) |P=0.252N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 3/50 (6%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 3/40.48 1/41.64 3/44.41 1/28.31 |1/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 7.4% 2.4% 6.8% 3.5% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 1/30 (3%) 3/32 (9%) 1/17 (6%) |1/30 (3%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 662 729 (T) 729 (T) 729 (T) |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.390N P=0.210N P=0.465N P=0.393N |P=0.323N P=0.487N P=0.487N P=0.536N | |POLY 3 | P=0.430N P=0.294N P=0.619N P=0.441N |P=0.307N P=0.498N P=0.490N P=0.503N | |POLY 1.5 | P=0.411N P=0.300N P=0.639N P=0.411N |P=0.308N P=0.499N P=0.493N P=0.501N | |POLY 6 | P=0.428N P=0.283N P=0.589N P=0.444N |P=0.304N P=0.495N P=0.487N P=0.507N | |LOGISTIC REGRESSION| P=0.420N P=0.272N P=0.556N P=0.430N |P=0.323N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.313N P=0.309N P=0.661N P=0.309N |P=0.308N P=0.500N P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.407N (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 19 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Lipoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 3/41.64 1/44.41 0/28.31 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 7.2% 2.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 3/30 (10%) 1/32 (3%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.415N P=0.200 P=0.594 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.466N P=0.124 P=0.520 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.454N P=0.121 P=0.511 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.450N P=0.131 P=0.534 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.200 P=0.594 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.366N P=0.121 P=0.500 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.306N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/40.60 0/41.64 2/44.41 2/28.31 |2/41.89 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 4.9% 0.0% 4.5% 7.1% |4.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 2/32 (6%) 2/17 (12%) |1/30 (3%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 606 --- 729 (T) 729 (T) |654 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.352 P=0.201N P=0.549N P=0.624 |P=0.120N P=0.233N P=0.227N P=0.263N | |POLY 3 | P=0.326 P=0.231N P=0.662N P=0.557 |P=0.113N P=0.236N P=0.227N P=0.241N | |POLY 1.5 | P=0.346 P=0.234N P=0.676N P=0.588 |P=0.114N P=0.237N P=0.230N P=0.239N | |POLY 6 | P=0.323 P=0.224N P=0.638N P=0.554 |P=0.112N P=0.234N P=0.225N P=0.247N | |LOGISTIC REGRESSION| P=0.321 P=0.239N P=0.665N P=0.567 |P=0.115N P=0.237N P=0.232N P=0.240N | |COCH-ARM / FISHERS | P=0.444 P=0.247N P=0.691N P=0.691N |P=0.116N P=0.247N P=0.247N P=0.253N | |ORDER RESTRICTED | P=0.294 (e) (e) (e) |P=0.031N* (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 20 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell | | Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 4/40.64 2/41.64 4/44.41 1/28.31 |1/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 9.8% 4.8% 9.0% 3.5% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 2/30 (7%) 4/32 (13%) 1/17 (6%) |1/30 (3%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 662 729 (T) 729 (T) 729 (T) |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.249N P=0.224N P=0.421N P=0.272N |P=0.323N P=0.487N P=0.487N P=0.536N | |POLY 3 | P=0.314N P=0.325N P=0.594N P=0.307N |P=0.307N P=0.498N P=0.490N P=0.503N | |POLY 1.5 | P=0.291N P=0.332N P=0.617N P=0.276N |P=0.308N P=0.499N P=0.493N P=0.501N | |POLY 6 | P=0.313N P=0.312N P=0.561N P=0.311N |P=0.304N P=0.495N P=0.487N P=0.507N | |LOGISTIC REGRESSION| P=0.278N P=0.296N P=0.526N P=0.293N |P=0.323N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.186N P=0.339N P=0.643N P=0.181N |P=0.308N P=0.500N P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.285N (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 4/40.64 2/41.64 4/44.41 1/28.31 |1/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 9.8% 4.8% 9.0% 3.5% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 2/30 (7%) 4/32 (13%) 1/17 (6%) |1/30 (3%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 662 729 (T) 729 (T) 729 (T) |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.249N P=0.224N P=0.421N P=0.272N |P=0.323N P=0.487N P=0.487N P=0.536N | |POLY 3 | P=0.314N P=0.325N P=0.594N P=0.307N |P=0.307N P=0.498N P=0.490N P=0.503N | |POLY 1.5 | P=0.291N P=0.332N P=0.617N P=0.276N |P=0.308N P=0.499N P=0.493N P=0.501N | |POLY 6 | P=0.313N P=0.312N P=0.561N P=0.311N |P=0.304N P=0.495N P=0.487N P=0.507N | |LOGISTIC REGRESSION| P=0.278N P=0.296N P=0.526N P=0.293N |P=0.323N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.186N P=0.339N P=0.643N P=0.181N |P=0.308N P=0.500N P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.285N (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 21 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 36/50 (72%) 37/50 (74%) 31/50 (62%) 22/50 (44%) | | |POLY-3 RATE (b) | 36/45.13 37/44.91 31/46.60 22/30.15 | | |POLY-3 PERCENT (g) | 79.8% 82.4% 66.5% 73.0% | | |TERMINAL (d) | 18/20 (90%) 26/30 (87%) 22/32 (69%) 15/17 (88%) | | |FIRST INCIDENCE | 533 571 444 606 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060N P=0.087N P=0.003N** P=0.123N | | |POLY 3 | P=0.111N P=0.479 P=0.101N P=0.330N | | |POLY 1.5 | P=0.051N P=0.483 P=0.137N P=0.134N | | |POLY 6 | P=0.124N P=0.497 P=0.069N P=0.444N | | |LOGISTIC REGRESSION| P=0.106N P=0.583 P=0.062N P=0.256N | | |COCH-ARM / FISHERS | P<0.001N** P=0.500 P=0.198N P=0.004N** | | |ORDER RESTRICTED | P=0.182N (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 9/50 (18%) 8/50 (16%) 4/50 (8%) |3/50 (6%) 2/50 (4%) 6/50 (12%) 6/49 (12%) | |POLY-3 RATE (b) | 5/40.29 9/43.03 8/44.95 4/28.73 |3/41.61 2/42.13 6/43.92 6/41.99 | |POLY-3 PERCENT (g) | 12.4% 20.9% 17.8% 13.9% |7.2% 4.8% 13.7% 14.3% | |TERMINAL (d) | 4/20 (20%) 4/30 (13%) 5/32 (16%) 3/17 (18%) |3/30 (10%) 1/32 (3%) 4/32 (13%) 3/25 (12%) | |FIRST INCIDENCE | 701 593 645 607 |729 (T) 703 703 593 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.491N P=0.380 P=0.580 P=0.620N |P=0.065 P=0.469N P=0.278 P=0.186 | |POLY 3 | P=0.508 P=0.227 P=0.349 P=0.569 |P=0.107 P=0.494N P=0.268 P=0.245 | |POLY 1.5 | P=0.535N P=0.209 P=0.314 P=0.609 |P=0.107 P=0.498N P=0.260 P=0.244 | |POLY 6 | P=0.526 P=0.266 P=0.406 P=0.575 |P=0.102 P=0.487N P=0.277 P=0.241 | |LOGISTIC REGRESSION| P=0.555N P=0.219 P=0.435 P=0.577 |P=0.095 P=0.475N P=0.279 P=0.233 | |COCH-ARM / FISHERS | P=0.309N P=0.194 P=0.277 P=0.500N |P=0.100 P=0.500N P=0.243 P=0.233 | |ORDER RESTRICTED | P=0.454 (e) (e) (e) |P=0.160 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 22 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 2/50 (4%) 3/49 (6%) | |POLY-3 RATE (b) | 5/40.69 1/41.64 2/44.41 0/28.31 |2/41.79 0/42.03 2/43.75 3/41.89 | |POLY-3 PERCENT (g) | 12.3% 2.4% 4.5% 0.0% |4.8% 0.0% 4.6% 7.2% | |TERMINAL (d) | 3/20 (15%) 1/30 (3%) 2/32 (6%) 0/17 (0%) |1/30 (3%) 0/32 (0%) 2/32 (6%) 0/25 (0%) | |FIRST INCIDENCE | 593 729 (T) 729 (T) --- |682 --- 729 (T) 617 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.026N* P=0.046N* P=0.089N P=0.057N |P=0.203 P=0.226N P=0.662N P=0.471 | |POLY 3 | P=0.038N* P=0.094N P=0.181N P=0.075N |P=0.236 P=0.236N P=0.678N P=0.501 | |POLY 1.5 | P=0.036N* P=0.098N P=0.197N P=0.063N |P=0.237 P=0.237N P=0.682N P=0.501 | |POLY 6 | P=0.036N* P=0.087N P=0.159N P=0.076N |P=0.231 P=0.233N P=0.675N P=0.496 | |LOGISTIC REGRESSION| P=0.036N* P=0.087N P=0.153N P=0.069N |P=0.233 P=0.235N P=0.672N P=0.490 | |COCH-ARM / FISHERS | P=0.025N* P=0.102N P=0.218N P=0.028N* |P=0.230 P=0.247N P=0.691N P=0.490 | |ORDER RESTRICTED | P=0.024N* (e) (e) (e) |P=0.216 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 10/50 (20%) 9/50 (18%) 4/50 (8%) |5/50 (10%) 2/50 (4%) 8/50 (16%) 9/49 (18%) | |POLY-3 RATE (b) | 10/40.80 10/43.03 9/44.95 4/28.73 |5/41.79 2/42.13 8/43.92 9/42.81 | |POLY-3 PERCENT (g) | 24.5% 23.2% 20.0% 13.9% |12.0% 4.8% 18.2% 21.0% | |TERMINAL (d) | 7/20 (35%) 5/30 (17%) 6/32 (19%) 3/17 (18%) |4/30 (13%) 1/32 (3%) 6/32 (19%) 3/25 (12%) | |FIRST INCIDENCE | 593 593 645 607 |682 703 703 593 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.113N P=0.323N P=0.164N P=0.143N |P=0.029 * P=0.193N P=0.327 P=0.150 | |POLY 3 | P=0.172N P=0.548N P=0.405N P=0.222N |P=0.054 P=0.212N P=0.307 P=0.203 | |POLY 1.5 | P=0.147N P=0.575N P=0.449N P=0.183N |P=0.053 P=0.215N P=0.298 P=0.198 | |POLY 6 | P=0.160N P=0.495N P=0.339N P=0.218N |P=0.053 P=0.206N P=0.315 P=0.205 | |LOGISTIC REGRESSION| P=0.153N P=0.548N P=0.314N P=0.210N |P=0.047 * P=0.201N P=0.323 P=0.187 | |COCH-ARM / FISHERS | P=0.050N P=0.598N P=0.500N P=0.074N |P=0.048 * P=0.218N P=0.277 P=0.183 | |ORDER RESTRICTED | P=0.259N (e) (e) (e) |P=0.067 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 23 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 1/40.18 0/41.64 0/44.41 0/28.31 |0/41.61 2/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% |0.0% 4.8% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |0/30 (0%) 2/32 (6%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.311N P=0.419N P=0.406N P=0.532N |P=0.441N P=0.252 (e) (e) | |POLY 3 | P=0.240N P=0.493N P=0.480N P=0.568N |P=0.402N P=0.239 (e) (e) | |POLY 1.5 | P=0.260N P=0.497N P=0.489N P=0.554N |P=0.403N P=0.238 (e) (e) | |POLY 6 | P=0.233N P=0.485N P=0.466N P=0.568N |P=0.402N P=0.242 (e) (e) | |LOGISTIC REGRESSION| P=0.311N (e) (e) (e) |(e) P=0.252 (e) (e) | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.409N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.193N (e) (e) (e) |P=0.252N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 1/40.18 0/41.64 0/44.41 0/28.31 |1/41.61 2/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% |2.4% 4.8% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 0/17 (0%) |1/30 (3%) 2/32 (6%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |729 (T) 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.311N P=0.419N P=0.406N P=0.532N |P=0.212N P=0.523 P=0.487N P=0.536N | |POLY 3 | P=0.240N P=0.493N P=0.480N P=0.568N |P=0.187N P=0.503 P=0.490N P=0.503N | |POLY 1.5 | P=0.260N P=0.497N P=0.489N P=0.554N |P=0.187N P=0.501 P=0.493N P=0.501N | |POLY 6 | P=0.233N P=0.485N P=0.466N P=0.568N |P=0.187N P=0.508 P=0.487N P=0.507N | |LOGISTIC REGRESSION| P=0.311N (e) (e) (e) |P=0.212N P=0.523 (e) (e) | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.191N P=0.500 P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.193N (e) (e) (e) |P=0.171N (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 24 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Tongue | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 1/44.41 0/28.31 |2/41.61 0/42.03 1/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.8% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 1/32 (3%) 0/17 (0%) |2/30 (7%) 0/32 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |729 (T) --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.689 (e) P=0.594 (e) |P=0.212N P=0.224N P=0.477N P=0.279N | |POLY 3 | P=0.496 (e) P=0.520 (e) |P=0.190N P=0.235N P=0.483N P=0.240N | |POLY 1.5 | P=0.547 (e) P=0.511 (e) |P=0.189N P=0.236N P=0.488N P=0.238N | |POLY 6 | P=0.481 (e) P=0.534 (e) |P=0.193N P=0.231N P=0.478N P=0.245N | |LOGISTIC REGRESSION| (e) (e) P=0.594 (e) |P=0.212N (e) P=0.477N (e) | |COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.191N P=0.247N P=0.500N P=0.253N | |ORDER RESTRICTED | P=0.415 (e) (e) (e) |P=0.076N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Uterus | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) | |POLY-3 RATE (b) | |0/41.61 0/42.03 0/43.75 2/41.07 | |POLY-3 PERCENT (g) | |0.0% 0.0% 0.0% 4.9% | |TERMINAL (d) | |0/30 (0%) 0/32 (0%) 0/32 (0%) 2/25 (8%) | |FIRST INCIDENCE | |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.031 * (e) (e) P=0.198 | |POLY 3 | |P=0.044 * (e) (e) P=0.234 | |POLY 1.5 | |P=0.044 * (e) (e) P=0.236 | |POLY 6 | |P=0.043 * (e) (e) P=0.228 | |LOGISTIC REGRESSION| |(e) (e) (e) P=0.198 | |COCH-ARM / FISHERS | |P=0.045 * (e) (e) P=0.242 | |ORDER RESTRICTED | |P=0.028 * (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 25 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |10/50 (20%) 10/50 (20%) 10/50 (20%) 10/49 (20%) | |POLY-3 RATE (b) | |10/43.56 10/42.41 10/44.90 10/42.91 | |POLY-3 PERCENT (g) | |23.0% 23.6% 22.3% 23.3% | |TERMINAL (d) | |6/30 (20%) 9/32 (28%) 6/32 (19%) 4/25 (16%) | |FIRST INCIDENCE | |394 621 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.412 P=0.554N P=0.524N P=0.494 | |POLY 3 | |P=0.545 P=0.574 P=0.570N P=0.586 | |POLY 1.5 | |P=0.548 P=0.581 P=0.577N P=0.591 | |POLY 6 | |P=0.530 P=0.573 P=0.566N P=0.571 | |LOGISTIC REGRESSION| |P=0.535 P=0.596N P=0.594 P=0.571 | |COCH-ARM / FISHERS | |P=0.526 P=0.598N P=0.598N P=0.579 | |ORDER RESTRICTED | |P=0.723N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or | | Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 13/50 (26%) 22/50 (44%) 13/50 (26%) 6/50 (12%) |9/50 (18%) 9/50 (18%) 7/50 (14%) 15/49 (31%) | |POLY-3 RATE (b) | 13/42.99 22/45.56 13/46.15 6/29.00 |9/42.76 9/42.48 7/44.82 15/43.32 | |POLY-3 PERCENT (g) | 30.2% 48.3% 28.2% 20.7% |21.1% 21.2% 15.6% 34.6% | |TERMINAL (d) | 3/20 (15%) 12/30 (40%) 6/32 (19%) 3/17 (18%) |4/30 (13%) 7/32 (22%) 3/32 (9%) 8/25 (32%) | |FIRST INCIDENCE | 522 522 556 606 |535 621 535 593 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.068N P=0.211 P=0.281N P=0.219N |P=0.042 * P=0.549N P=0.345N P=0.083 | |POLY 3 | P=0.112N P=0.059 P=0.507N P=0.270N |P=0.075 P=0.598 P=0.352N P=0.119 | |POLY 1.5 | P=0.077N P=0.051 P=0.546N P=0.203N |P=0.074 P=0.598 P=0.364N P=0.119 | |POLY 6 | P=0.114N P=0.080 P=0.449N P=0.292N |P=0.073 P=0.602 P=0.343N P=0.115 | |LOGISTIC REGRESSION| P=0.043N* P=0.046 * P=0.564 P=0.199N |P=0.071 P=0.595N P=0.378N P=0.114 | |COCH-ARM / FISHERS | P=0.010N* P=0.046 * P=0.590N P=0.062N |P=0.068 P=0.602N P=0.393N P=0.109 | |ORDER RESTRICTED | P=0.093N (e) (e) (e) |P=0.064 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 26 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/40.59 0/41.64 0/44.41 1/28.31 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 4.9% 0.0% 0.0% 3.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/30 (0%) 0/32 (0%) 1/17 (6%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 608 --- --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522N P=0.198N P=0.173N P=0.576N |(e) (e) (e) (e) | |POLY 3 | P=0.401N P=0.231N P=0.217N P=0.621N |(e) (e) (e) (e) | |POLY 1.5 | P=0.425N P=0.234N P=0.226N P=0.596N |(e) (e) (e) (e) | |POLY 6 | P=0.389N P=0.224N P=0.204N P=0.625N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.531N P=0.239N P=0.250N P=0.615N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.461N P=0.247N P=0.247N P=0.500N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.213N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 1/40.44 2/42.29 4/44.58 1/28.65 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 2.5% 4.7% 9.0% 3.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 2/32 (6%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 657 601 694 634 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.483 P=0.503 P=0.315 P=0.672 |(e) (e) (e) (e) | |POLY 3 | P=0.358 P=0.516 P=0.209 P=0.678 |(e) (e) (e) (e) | |POLY 1.5 | P=0.404 P=0.507 P=0.195 P=0.696 |(e) (e) (e) (e) | |POLY 6 | P=0.356 P=0.531 P=0.232 P=0.679 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.502 P=0.492 P=0.221 P=0.729 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.596 P=0.500 P=0.181 P=0.753N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.365 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 27 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 1/40.44 2/42.29 4/44.58 1/28.65 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 2.5% 4.7% 9.0% 3.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 2/32 (6%) 0/17 (0%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 657 601 694 634 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.483 P=0.503 P=0.315 P=0.672 |(e) (e) (e) (e) | |POLY 3 | P=0.358 P=0.516 P=0.209 P=0.678 |(e) (e) (e) (e) | |POLY 1.5 | P=0.404 P=0.507 P=0.195 P=0.696 |(e) (e) (e) (e) | |POLY 6 | P=0.356 P=0.531 P=0.232 P=0.679 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.502 P=0.492 P=0.221 P=0.729 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.596 P=0.500 P=0.181 P=0.753N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.365 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Osteosarcoma or Osteoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/40.18 0/41.64 0/44.41 2/28.51 |0/41.61 0/42.03 0/43.75 0/41.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/30 (0%) 0/32 (0%) 1/17 (6%) |0/30 (0%) 0/32 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- 676 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020 * (e) (e) P=0.180 |(e) (e) (e) (e) | |POLY 3 | P=0.038 * (e) (e) P=0.170 |(e) (e) (e) (e) | |POLY 1.5 | P=0.038 * (e) (e) P=0.182 |(e) (e) (e) (e) | |POLY 6 | P=0.039 * (e) (e) P=0.171 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.022 * (e) (e) P=0.165 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 28 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 47/50 (94%) 48/50 (96%) 50/50 (100%) 32/50 (64%) |44/50 (88%) 41/50 (82%) 41/50 (82%) 39/49 (80%) | |POLY-3 RATE (b) | 47/48.36 48/48.71 50/50.00 32/33.39 |44/46.95 41/46.52 41/47.91 39/46.61 | |POLY-3 PERCENT (g) | 97.2% 98.6% 100.0% 95.8% |93.7% 88.1% 85.6% 83.7% | |TERMINAL (d) | 20/20 (100%) 30/30 (100%) 32/32 (100%) 17/17 (100%)|29/30 (97%) 28/32 (88%) 28/32 (88%) 21/25 (84%) | |FIRST INCIDENCE | 522 444 444 290 |394 522 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.240N P=0.077N P=0.032N* P=0.277N |P=0.449 P=0.237N P=0.200N P=0.547 | |POLY 3 | P=0.602N P=0.637 P=0.321 P=0.677N |P=0.084N P=0.267N P=0.148N P=0.092N | |POLY 1.5 | P=0.021N* P=0.552 P=0.191 P=0.059N |P=0.096N P=0.284N P=0.179N P=0.109N | |POLY 6 | P=0.464 P=0.881 P=0.758 P=0.934 |P=0.094N P=0.222N P=0.130N P=0.091N | |LOGISTIC REGRESSION| P=0.364 P=0.477 P=0.160 P=0.570 |P=0.107N P=0.267N P=0.159N P=0.122N | |COCH-ARM / FISHERS | P<0.001N** P=0.500 P=0.121 P<0.001N** |P=0.190N P=0.288N P=0.288N P=0.194N | |ORDER RESTRICTED | P=0.125N (e) (e) (e) |P=0.087N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 34/50 (68%) 31/50 (62%) 27/50 (54%) 15/50 (30%) |22/50 (44%) 14/50 (28%) 16/50 (32%) 23/49 (47%) | |POLY-3 RATE (b) | 34/47.18 31/48.18 27/47.46 15/30.62 |22/45.65 14/43.24 16/45.88 23/45.42 | |POLY-3 PERCENT (g) | 72.1% 64.3% 56.9% 49.0% |48.2% 32.4% 34.9% 50.6% | |TERMINAL (d) | 12/20 (60%) 14/30 (47%) 15/32 (47%) 9/17 (53%) |9/30 (30%) 9/32 (28%) 9/32 (28%) 9/25 (36%) | |FIRST INCIDENCE | 463 485 556 319 |394 513 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.015N* P=0.117N P=0.010N* P=0.030N* |P=0.178 P=0.079N P=0.135N P=0.357 | |POLY 3 | P=0.020N* P=0.274N P=0.086N P=0.032N* |P=0.297 P=0.093N P=0.137N P=0.491 | |POLY 1.5 | P=0.006N** P=0.306N P=0.097N P=0.008N** |P=0.290 P=0.083N P=0.136N P=0.493 | |POLY 6 | P=0.033N* P=0.223N P=0.071N P=0.060N |P=0.292 P=0.108N P=0.148N P=0.471 | |LOGISTIC REGRESSION| P<0.001N** P=0.364N P=0.120N P=0.008N** |P=0.261 P=0.071N P=0.153N P=0.459 | |COCH-ARM / FISHERS | P<0.001N** P=0.338N P=0.109N P<0.001N** |P=0.256 P=0.072N P=0.151N P=0.463 | |ORDER RESTRICTED | P=0.038N* (e) (e) (e) |P=0.181 (e) (e) (e) | |=================================================================================================================================| Date: 01/03/05 EXPERIMENT: 93020 TEST: 07 Page 29 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - DIISOPROPYLCARBODIIMIDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG |0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 50/50 (100%) 50/50 (100%) 50/50 (100%) 33/50 (66%) |48/50 (96%) 45/50 (90%) 44/50 (88%) 45/49 (92%) | |POLY-3 RATE (b) | 50/50.00 50/50.00 50/50.00 33/34.31 |48/48.16 45/47.24 44/48.97 45/47.75 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 96.2% |99.7% 95.3% 89.9% 94.2% | |TERMINAL (d) | 20/20 (100%) 30/30 (100%) 32/32 (100%) 17/17 (100%)|30/30 (100%) 30/32 (94%) 28/32 (88%) 23/25 (92%) | |FIRST INCIDENCE | 463 444 444 290 |394 513 465 456 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.170N (e) (e) P=0.226N |P=0.304 P=0.237N P=0.162N P=0.397 | |POLY 3 | P<0.001N** (e) (e) P=0.131N |P=0.151N P=0.217N P=0.035N* P=0.143N | |POLY 1.5 | P<0.001N** (e) (e) P<0.001N** |P=0.165N P=0.195N P=0.044N* P=0.158N | |POLY 6 | P=0.737N (e) (e) P=1.000N |P=0.177N P=0.231N P=0.036N* P=0.175N | |LOGISTIC REGRESSION| P=0.093N (e) (e) P=0.364N |P=0.165N P=0.165N P=0.052N P=0.134N | |COCH-ARM / FISHERS | P<0.001N** (e) (e) P<0.001N** |P=0.337N P=0.218N P=0.134N P=0.329N | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) |P=0.054N (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).