TDMS Study 93020-08 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst DIISOPROPYLCARBODIIMIDE DATE: 07/19/04 EXPERIMENT: 93020 TEST: 08 TIME: 09:18:54 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-05451 ROUTE: SKIN APPLICATION NTP C#: 93020D PATHOLOGIST: FARNELL, DANIEL CAS: 693-13-0 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst DIISOPROPYLCARBODIIMIDE DATE: 07/19/04 EXPERIMENT: 93020 TEST: 08 TIME: 09:18:54 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-05451 ROUTE: SKIN APPLICATION NTP C#: 93020D PATHOLOGIST: FARNELL, DANIEL CAS: 693-13-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF DIISOPROPYLCARBODIIMIDE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Kidney Cyst Inflammation Metaplasia Focal Osseous Nephropathy Liver: Hepatocyte Clear Cell Focus Eosinophilic Focus Pancreas: Acinus Atrophy Focal Preputial Gland Cyst Skin: Site of Application - Dermis Inflammation Focal Skin: Site of Application - Epidermis Hyperplasia Skin: Subcutaneous Tissue Edema Stomach, Glandular Erosion =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Heart Thrombosis Kidney Metaplasia Focal Osseous Liver Eosinophilic Focus Infiltration Cellular Mixed Cell Liver: Hepatocyte Mixed Cell Focus Lymph Node, Mandibular Hyperplasia Lymphoid Lymph Node: Iliac Ectasia Hemorrhage Ovary Hemorrhage Spleen Hematopoietic Cell Proliferation Thymus Hyperplasia Lymphoid Thyroid Gland: Follicular Cell Hyperplasia Focal Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 2/50 (4%) 2/49 (4%) |2/50 (4%) 1/50 (2%) 1/49 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 3/46.83 2/46.60 2/44.84 2/42.72 |2/42.68 1/44.63 1/43.22 3/45.70 | |POLY-3 PERCENT (g) | 6.4% 4.3% 4.5% 4.7% |4.7% 2.2% 2.3% 6.6% | |TERMINAL (d) | 3/39 (8%) 1/40 (3%) 2/38 (5%) 2/36 (6%) |2/33 (6%) 0/33 (0%) 1/38 (3%) 2/40 (5%) | |FIRST INCIDENCE | 729 (T) 545 729 (T) 729 (T) |729 (T) 12 729 (T) 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.472N P=0.491N P=0.512N P=0.537N |P=0.386 P=0.500N P=0.451N P=0.575 | |POLY 3 | P=0.469N P=0.502N P=0.520N P=0.542N |P=0.340 P=0.484N P=0.496N P=0.531 | |POLY 1.5 | P=0.464N P=0.505N P=0.519N P=0.536N |P=0.332 P=0.485N P=0.502N P=0.521 | |POLY 6 | P=0.474N P=0.498N P=0.520N P=0.546N |P=0.351 P=0.488N P=0.489N P=0.543 | |LOGISTIC REGRESSION| P=0.461N P=0.489N P=0.512N P=0.537N |P=0.296 P=0.536N P=0.451N P=0.508 | |COCH-ARM / FISHERS | P=0.440N P=0.500N P=0.500N P=0.510N |P=0.324 P=0.500N P=0.508N P=0.500 | |ORDER RESTRICTED | P=0.533N (e) (e) (e) |P=0.318 (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 Cortex | | Cytoplasmic Alteration Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 5/50 (10%) 7/50 (14%) 4/49 (8%) |1/50 (2%) 2/50 (4%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 9/46.83 5/46.01 7/44.84 4/42.72 |1/42.68 2/43.63 1/43.38 0/45.13 | |POLY-3 PERCENT (g) | 19.2% 10.9% 15.6% 9.4% |2.3% 4.6% 2.3% 0.0% | |TERMINAL (d) | 9/39 (23%) 5/40 (13%) 7/38 (18%) 4/36 (11%) |1/33 (3%) 2/33 (6%) 0/38 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.167N P=0.176N P=0.413N P=0.146N |P=0.208N P=0.500 P=0.736N P=0.462N | |POLY 3 | P=0.169N P=0.202N P=0.429N P=0.153N |P=0.235N P=0.508 P=0.757N P=0.489N | |POLY 1.5 | P=0.164N P=0.204N P=0.428N P=0.149N |P=0.240N P=0.507 P=0.760 P=0.492N | |POLY 6 | P=0.174N P=0.200N P=0.430N P=0.157N |P=0.229N P=0.503 P=0.752N P=0.485N | |LOGISTIC REGRESSION| P=0.167N P=0.176N P=0.413N P=0.146N |P=0.230N P=0.500 P=0.761N (e) | |COCH-ARM / FISHERS | P=0.139N P=0.194N P=0.393N P=0.125N |P=0.248N P=0.500 P=0.747 P=0.500N | |ORDER RESTRICTED | P=0.139N (e) (e) (e) |P=0.218N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Hyperostosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |3/50 (6%) 1/50 (2%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 2/46.92 2/46.01 1/44.84 0/43.48 |3/43.07 1/43.63 1/44.38 2/45.13 | |POLY-3 PERCENT (g) | 4.3% 4.4% 2.2% 0.0% |7.0% 2.3% 2.3% 4.4% | |TERMINAL (d) | 1/39 (3%) 2/40 (5%) 1/38 (3%) 0/36 (0%) |2/33 (6%) 1/33 (3%) 0/39 (0%) 2/40 (5%) | |FIRST INCIDENCE | 706 729 (T) 729 (T) --- |619 729 (T) 690 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.141N P=0.689N P=0.512N P=0.260N |P=0.407N P=0.304N P=0.272N P=0.428N | |POLY 3 | P=0.138N P=0.687 P=0.516N P=0.255N |P=0.464N P=0.300N P=0.294N P=0.479N | |POLY 1.5 | P=0.136N P=0.686 P=0.515N P=0.251N |P=0.469N P=0.299N P=0.300N P=0.485N | |POLY 6 | P=0.141N P=0.687 P=0.517N P=0.258N |P=0.456N P=0.307N P=0.289N P=0.473N | |LOGISTIC REGRESSION| P=0.140N P=0.690 P=0.515N P=0.254N |P=0.457N P=0.299N P=0.302N P=0.481N | |COCH-ARM / FISHERS | P=0.125N P=0.691N P=0.500N P=0.247N |P=0.474N P=0.309N P=0.309N P=0.500N | |ORDER RESTRICTED | P=0.166N (e) (e) (e) |P=0.273N (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 | | | | | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/49 (18%) 13/50 (26%) 12/50 (24%) 7/50 (14%) |14/49 (29%) 5/50 (10%) 10/50 (20%) 2/49 (4%) | |POLY-3 RATE (b) | 9/46.49 13/46.24 12/45.27 7/44.68 |14/44.39 5/44.15 10/45.05 2/44.17 | |POLY-3 PERCENT (g) | 19.4% 28.1% 26.5% 15.7% |31.5% 11.3% 22.2% 4.5% | |TERMINAL (d) | 7/39 (18%) 12/40 (30%) 10/38 (26%) 3/36 (8%) |8/33 (24%) 3/33 (9%) 8/39 (21%) 2/40 (5%) | |FIRST INCIDENCE | 682 670 653 558 |488 625 560 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.337N P=0.253 P=0.288 P=0.470N |P=0.002N** P=0.027N* P=0.161N P<0.001N** | |POLY 3 | P=0.290N P=0.228 P=0.286 P=0.426N |P=0.003N** P=0.018N* P=0.224N P<0.001N** | |POLY 1.5 | P=0.284N P=0.230 P=0.290 P=0.420N |P=0.003N** P=0.016N* P=0.226N P<0.001N** | |POLY 6 | P=0.293N P=0.225 P=0.283 P=0.429N |P=0.002N** P=0.021N* P=0.225N P<0.001N** | |LOGISTIC REGRESSION| P=0.294N P=0.225 P=0.279 P=0.407N |P=0.003N** P=0.018N* P=0.219N P<0.001N** | |COCH-ARM / FISHERS | P=0.234N P=0.251 P=0.331 P=0.376N |P=0.004N** P=0.017N* P=0.224N P<0.001N** | |ORDER RESTRICTED | P=0.241N (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Compression Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.84 0/43.48 |2/43.44 2/44.39 0/44.22 1/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.6% 4.5% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |521 540 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.267N P=0.680N P=0.226N P=0.456N | |POLY 3 | (e) (e) (e) (e) |P=0.291N P=0.686N P=0.233N P=0.487N | |POLY 1.5 | (e) (e) (e) (e) |P=0.293N P=0.686N P=0.236N P=0.490N | |POLY 6 | (e) (e) (e) (e) |P=0.288N P=0.691N P=0.231N P=0.483N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.307N P=0.680 P=0.236N P=0.516N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.296N P=0.691N P=0.247N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.257N (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 | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.84 0/43.48 |1/42.68 2/44.91 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 4.5% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 12 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.177N P=0.500 P=0.467N P=0.462N | |POLY 3 | (e) (e) (e) (e) |P=0.179N P=0.518 P=0.493N P=0.489N | |POLY 1.5 | (e) (e) (e) (e) |P=0.182N P=0.516 P=0.497N P=0.492N | |POLY 6 | (e) (e) (e) (e) |P=0.177N P=0.516 P=0.489N P=0.485N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.201N P=0.459 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.188N P=0.500 P=0.500N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.167N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Eye | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/46 (2%) 0/46 (0%) 0/47 (0%) 0/44 (0%) |1/47 (2%) 0/48 (0%) 2/49 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 1/44.17 0/42.61 0/42.82 0/40.40 |1/41.09 0/41.91 2/44.11 0/44.17 | |POLY-3 PERCENT (g) | 2.3% 0.0% 0.0% 0.0% |2.4% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/32 (0%) 1/39 (3%) 0/40 (0%) | |FIRST INCIDENCE | 725 --- --- --- |603 --- 614 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.319N P=0.500N P=0.510N P=0.521N |P=0.437N P=0.500N P=0.522 P=0.496N | |POLY 3 | P=0.305N P=0.507N P=0.506N P=0.518N |P=0.440N P=0.496N P=0.525 P=0.486N | |POLY 1.5 | P=0.306N P=0.506N P=0.505N P=0.516N |P=0.444N P=0.494N P=0.519 P=0.487N | |POLY 6 | P=0.304N P=0.508N P=0.508N P=0.520N |P=0.434N P=0.502N P=0.530 P=0.485N | |LOGISTIC REGRESSION| P=0.317N P=0.508N P=0.508N P=0.521N |P=0.458N P=0.503N P=0.514 P=0.510N | |COCH-ARM / FISHERS | P=0.309N P=0.500N P=0.495N P=0.511N |P=0.451N P=0.495N P=0.516 P=0.490N | |ORDER RESTRICTED | P=0.137N (e) (e) (e) |P=0.312N (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 | | | | | |=================================================================================================================================| | | |Eye: Cornea | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/46 (4%) 3/46 (7%) 1/47 (2%) 3/44 (7%) |0/47 (0%) 1/48 (2%) 0/49 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/44.16 3/42.61 1/42.97 3/40.40 |0/40.66 1/41.91 0/43.71 0/44.17 | |POLY-3 PERCENT (g) | 4.5% 7.0% 2.3% 7.4% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 2/39 (5%) 3/40 (8%) 0/38 (0%) 3/36 (8%) |0/33 (0%) 1/32 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 690 729 (T) |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.434 P=0.512 P=0.512N P=0.463 |P=0.533N P=0.494 (e) (e) | |POLY 3 | P=0.439 P=0.484 P=0.509N P=0.460 |P=0.557N P=0.506 (e) (e) | |POLY 1.5 | P=0.443 P=0.486 P=0.508N P=0.464 |P=0.558N P=0.507 (e) (e) | |POLY 6 | P=0.434 P=0.482 P=0.511N P=0.454 |P=0.558N P=0.502 (e) (e) | |LOGISTIC REGRESSION| P=0.433 P=0.512 P=0.506N P=0.463 |(e) P=0.494 (e) (e) | |COCH-ARM / FISHERS | P=0.457 P=0.500 P=0.492N P=0.479 |P=0.561N P=0.505 (e) (e) | |ORDER RESTRICTED | P=0.441 (e) (e) (e) |P=0.372N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Gallbladder | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/45 (2%) 1/42 (2%) 2/43 (5%) 0/41 (0%) |0/42 (0%) 1/47 (2%) 0/42 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 1/43.81 1/40.34 2/41.14 0/38.54 |0/36.97 1/41.56 0/39.63 0/42.83 | |POLY-3 PERCENT (g) | 2.3% 2.5% 4.9% 0.0% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 1/39 (3%) 1/37 (3%) 0/36 (0%) |0/31 (0%) 1/33 (3%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 496 --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.392N P=0.762 P=0.481 P=0.516N |P=0.528N P=0.512 (e) (e) | |POLY 3 | P=0.400N P=0.742 P=0.478 P=0.526N |P=0.550N P=0.523 (e) (e) | |POLY 1.5 | P=0.398N P=0.741 P=0.478 P=0.525N |P=0.552N P=0.523 (e) (e) | |POLY 6 | P=0.402N P=0.743 P=0.478 P=0.527N |P=0.550N P=0.521 (e) (e) | |LOGISTIC REGRESSION| P=0.365N P=0.762 P=0.550 (e) |(e) P=0.512 (e) (e) | |COCH-ARM / FISHERS | P=0.388N P=0.735 P=0.483 P=0.523N |P=0.556N P=0.528 (e) (e) | |ORDER RESTRICTED | P=0.280N (e) (e) (e) |P=0.378N (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 | | | | | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 2/49 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.83 0/46.01 0/44.84 1/43.48 |0/42.68 2/43.06 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 2.1% 0.0% 0.0% 2.3% |0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 0/38 (0%) 1/36 (3%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- --- 729 (T) |--- 690 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.577 P=0.495N P=0.505N P=0.744 |P=0.372N P=0.237 (e) (e) | |POLY 3 | P=0.585 P=0.504N P=0.509N P=0.744 |P=0.388N P=0.239 (e) (e) | |POLY 1.5 | P=0.587 P=0.504N P=0.508N P=0.747 |P=0.393N P=0.238 (e) (e) | |POLY 6 | P=0.582 P=0.503N P=0.509N P=0.741 |P=0.385N P=0.237 (e) (e) | |LOGISTIC REGRESSION| P=0.577 (e) (e) P=0.744 |P=0.395N P=0.238 (e) (e) | |COCH-ARM / FISHERS | P=0.595 P=0.500N P=0.500N P=0.753N |P=0.404N P=0.242 (e) (e) | |ORDER RESTRICTED | P=0.380 (e) (e) (e) |P=0.238N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Harderian Gland: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 3/50 (6%) 1/50 (2%) |1/50 (2%) 1/49 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 3/46.83 0/46.01 3/45.53 1/43.48 |1/42.68 1/42.91 1/44.22 0/45.13 | |POLY-3 PERCENT (g) | 6.4% 0.0% 6.6% 2.3% |2.3% 2.3% 2.3% 0.0% | |TERMINAL (d) | 3/39 (8%) 0/40 (0%) 2/38 (5%) 1/36 (3%) |1/33 (3%) 1/33 (3%) 1/39 (3%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- 493 729 (T) |729 (T) 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.406N P=0.117N P=0.649 P=0.334N |P=0.266N P=0.762 P=0.724N P=0.462N | |POLY 3 | P=0.396N P=0.122N P=0.649 P=0.332N |P=0.300N P=0.760N P=0.753N P=0.489N | |POLY 1.5 | P=0.391N P=0.122N P=0.647 P=0.328N |P=0.304N P=0.760N P=0.757N P=0.492N | |POLY 6 | P=0.401N P=0.121N P=0.652 P=0.337N |P=0.295N P=0.760 P=0.749N P=0.485N | |LOGISTIC REGRESSION| P=0.376N (e) P=0.657N P=0.334N |P=0.266N P=0.762 P=0.724N (e) | |COCH-ARM / FISHERS | P=0.373N P=0.121N P=0.661N P=0.309N |P=0.310N P=0.747 P=0.753N P=0.500N | |ORDER RESTRICTED | P=0.248N (e) (e) (e) |P=0.317N (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 | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 3/50 (6%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 1/45.02 1/44.19 |0/42.68 3/43.91 1/43.71 1/45.56 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 2.3% |0.0% 6.8% 2.3% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 2/33 (6%) 0/38 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 681 484 |--- 653 584 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.219 (e) P=0.491 P=0.488 |P=0.613N P=0.123 P=0.504 P=0.514 | |POLY 3 | P=0.222 (e) P=0.492 P=0.488 |P=0.623N P=0.124 P=0.505 P=0.513 | |POLY 1.5 | P=0.224 (e) P=0.492 P=0.490 |P=0.613 P=0.123 P=0.500 P=0.509 | |POLY 6 | P=0.220 (e) P=0.493 P=0.487 |P=0.614N P=0.122 P=0.510 P=0.518 | |LOGISTIC REGRESSION| P=0.277 (e) P=0.508 P=0.652 |P=0.583 P=0.123 P=0.499 P=0.480 | |COCH-ARM / FISHERS | P=0.236 (e) P=0.500 P=0.500 |P=0.590 P=0.121 P=0.495 P=0.500 | |ORDER RESTRICTED | P=0.240 (e) (e) (e) |P=0.227 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Heart | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |4/50 (8%) 0/50 (0%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 1/46.01 0/44.84 0/43.48 |4/44.10 0/43.63 2/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |9.1% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/39 (0%) 1/40 (3%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 0/33 (0%) 1/38 (3%) 0/40 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- |44 --- 67 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.582N P=0.505 (e) (e) |P=0.054N P=0.068N P=0.312N P=0.055N | |POLY 3 | P=0.575N P=0.496 (e) (e) |P=0.057N P=0.061N P=0.336N P=0.057N | |POLY 1.5 | P=0.574N P=0.496 (e) (e) |P=0.059N P=0.061N P=0.342N P=0.059N | |POLY 6 | P=0.575N P=0.497 (e) (e) |P=0.054N P=0.064N P=0.330N P=0.056N | |LOGISTIC REGRESSION| (e) P=0.505 (e) (e) |P=0.066N P=0.067N P=0.311N P=0.078N | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.062N P=0.059N P=0.349N P=0.059N | |ORDER RESTRICTED | P=0.391N (e) (e) (e) |P=0.011N* (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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 2/49 (4%) 1/50 (2%) |0/50 (0%) 2/49 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.28 2/46.01 2/44.29 1/43.48 |0/42.68 2/42.80 1/44.22 0/45.13 | |POLY-3 PERCENT (g) | 4.3% 4.4% 4.5% 2.3% |0.0% 4.7% 2.3% 0.0% | |TERMINAL (d) | 2/39 (5%) 2/40 (5%) 2/38 (5%) 1/36 (3%) |0/33 (0%) 2/33 (6%) 1/39 (3%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.407N P=0.686N P=0.686 P=0.528N |P=0.406N P=0.238 P=0.533 (e) | |POLY 3 | P=0.398N P=0.692 P=0.678 P=0.522N |P=0.438N P=0.238 P=0.507 (e) | |POLY 1.5 | P=0.392N P=0.692 P=0.678 P=0.516N |P=0.445N P=0.237 P=0.503 (e) | |POLY 6 | P=0.405N P=0.691 P=0.678 P=0.528N |P=0.432N P=0.235 P=0.511 (e) | |LOGISTIC REGRESSION| P=0.407N P=0.686N P=0.686 P=0.528N |(e) P=0.238 P=0.533 (e) | |COCH-ARM / FISHERS | P=0.367N P=0.684N P=0.691N P=0.492N |P=0.459N P=0.242 P=0.500 (e) | |ORDER RESTRICTED | P=0.483N (e) (e) (e) |P=0.315N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 10/48 (21%) 5/50 (10%) 3/48 (6%) |1/49 (2%) 0/49 (0%) 4/50 (8%) 0/49 (0%) | |POLY-3 RATE (b) | 3/45.74 10/44.38 5/44.90 3/41.93 |1/41.96 0/42.91 4/44.51 0/44.17 | |POLY-3 PERCENT (g) | 6.6% 22.5% 11.1% 7.2% |2.4% 0.0% 9.0% 0.0% | |TERMINAL (d) | 3/39 (8%) 10/40 (25%) 4/38 (11%) 3/36 (8%) |1/33 (3%) 0/33 (0%) 3/39 (8%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 715 729 (T) |729 (T) --- 653 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.336N P=0.039 * P=0.341 P=0.626 |P=0.469N P=0.500N P=0.227 P=0.462N | |POLY 3 | P=0.341N P=0.029 * P=0.346 P=0.622 |P=0.507N P=0.496N P=0.197 P=0.490N | |POLY 1.5 | P=0.327N P=0.030 * P=0.351 P=0.630 |P=0.515N P=0.496N P=0.191 P=0.493N | |POLY 6 | P=0.355N P=0.029 * P=0.341 P=0.614 |P=0.495N P=0.498N P=0.203 P=0.487N | |LOGISTIC REGRESSION| P=0.347N P=0.039 * P=0.329 P=0.626 |P=0.512N (e) P=0.195 (e) | |COCH-ARM / FISHERS | P=0.275N P=0.035 * P=0.381 P=0.661N |P=0.530N P=0.500N P=0.187 P=0.500N | |ORDER RESTRICTED | P=0.230N (e) (e) (e) |P=0.219N (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 | | | | | |=================================================================================================================================| | | |Kidney | | Hydronephrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/48 (2%) 0/50 (0%) 0/48 (0%) |0/49 (0%) 0/49 (0%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 2/45.74 1/44.38 0/44.84 0/41.93 |0/41.96 0/42.91 1/44.22 1/44.56 | |POLY-3 PERCENT (g) | 4.4% 2.3% 0.0% 0.0% |0.0% 0.0% 2.3% 2.2% | |TERMINAL (d) | 2/39 (5%) 1/40 (3%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 1/39 (3%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |--- --- 729 (T) 619 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.109N P=0.491N P=0.244N P=0.256N |P=0.257 (e) P=0.533 P=0.505 | |POLY 3 | P=0.102N P=0.511N P=0.242N P=0.257N |P=0.252 (e) P=0.510 P=0.512 | |POLY 1.5 | P=0.101N P=0.509N P=0.240N P=0.253N |P=0.246 (e) P=0.507 P=0.508 | |POLY 6 | P=0.103N P=0.511N P=0.244N P=0.261N |P=0.260 (e) P=0.514 P=0.516 | |LOGISTIC REGRESSION| P=0.109N P=0.491N (e) (e) |P=0.234 (e) P=0.533 P=0.484 | |COCH-ARM / FISHERS | P=0.099N P=0.500N P=0.237N P=0.247N |P=0.235 (e) P=0.505 P=0.500 | |ORDER RESTRICTED | P=0.087N (e) (e) (e) |P=0.261 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Kidney | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/50 (0%) 0/48 (0%) |2/49 (4%) 2/49 (4%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 0/45.74 0/44.38 0/44.84 0/41.93 |2/42.08 2/42.91 1/44.22 1/44.17 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.8% 4.7% 2.3% 2.3% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 2/33 (6%) 1/39 (3%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |698 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.273N P=0.688 P=0.452N P=0.441N | |POLY 3 | (e) (e) (e) (e) |P=0.324N P=0.687N P=0.483N P=0.483N | |POLY 1.5 | (e) (e) (e) (e) |P=0.329N P=0.687N P=0.488N P=0.488N | |POLY 6 | (e) (e) (e) (e) |P=0.319N P=0.693N P=0.478N P=0.479N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.305N P=0.695 P=0.478N P=0.478N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.336N P=0.691N P=0.492N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.420N (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 | | | | | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 1/50 (2%) 1/48 (2%) |3/49 (6%) 2/49 (4%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 2/45.74 3/44.38 1/44.84 1/41.93 |3/41.96 2/42.91 1/44.22 1/44.17 | |POLY-3 PERCENT (g) | 4.4% 6.8% 2.2% 2.4% |7.2% 4.7% 2.3% 2.3% | |TERMINAL (d) | 2/39 (5%) 3/40 (8%) 1/38 (3%) 1/36 (3%) |3/33 (9%) 2/33 (6%) 1/39 (3%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.308N P=0.512 P=0.509N P=0.528N |P=0.145N P=0.500N P=0.247N P=0.239N | |POLY 3 | P=0.305N P=0.486 P=0.507N P=0.530N |P=0.189N P=0.490N P=0.286N P=0.287N | |POLY 1.5 | P=0.299N P=0.488 P=0.504N P=0.524N |P=0.193N P=0.490N P=0.292N P=0.292N | |POLY 6 | P=0.310N P=0.485 P=0.511N P=0.536N |P=0.184N P=0.496N P=0.281N P=0.281N | |LOGISTIC REGRESSION| P=0.308N P=0.512 P=0.509N P=0.528N |P=0.145N P=0.500N P=0.247N P=0.239N | |COCH-ARM / FISHERS | P=0.276N P=0.500 P=0.485N P=0.500N |P=0.198N P=0.500N P=0.301N P=0.309N | |ORDER RESTRICTED | P=0.352N (e) (e) (e) |P=0.198N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/50 (0%) 3/48 (6%) |1/49 (2%) 1/49 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/45.74 0/44.38 0/44.84 3/43.00 |1/42.35 1/42.91 0/44.22 0/44.17 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.0% |2.4% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 1/36 (3%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- 558 |619 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * (e) (e) P=0.112 |P=0.219N P=0.758N P=0.500N P=0.495N | |POLY 3 | P=0.010 * (e) (e) P=0.108 |P=0.233N P=0.758N P=0.491N P=0.492N | |POLY 1.5 | P=0.010 * (e) (e) P=0.109 |P=0.234N P=0.757N P=0.494N P=0.494N | |POLY 6 | P=0.010 * (e) (e) P=0.107 |P=0.232N P=0.759 P=0.490N P=0.490N | |LOGISTIC REGRESSION| P=0.014 * (e) (e) P=0.151 |P=0.235N P=0.762 P=0.496N P=0.516N | |COCH-ARM / FISHERS | P=0.012 * (e) (e) P=0.121 |P=0.235N P=0.753N P=0.495N P=0.500N | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) |P=0.242N (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 | | | | | |=================================================================================================================================| | | |Kidney | | Metaplasia Focal Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/48 (8%) 2/48 (4%) 1/50 (2%) 0/48 (0%) |5/49 (10%) 2/49 (4%) 0/50 (0%) 1/49 (2%) | |POLY-3 RATE (b) | 4/45.74 2/44.53 1/44.90 0/41.93 |5/42.40 2/42.91 0/44.22 1/44.17 | |POLY-3 PERCENT (g) | 8.8% 4.5% 2.2% 0.0% |11.8% 4.7% 0.0% 2.3% | |TERMINAL (d) | 4/39 (10%) 1/40 (3%) 0/38 (0%) 0/36 (0%) |3/33 (9%) 2/33 (6%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 691 715 --- |619 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.037N* P=0.330N P=0.191N P=0.073N |P=0.030N* P=0.222N P=0.026N* P=0.075N | |POLY 3 | P=0.032N* P=0.350N P=0.184N P=0.072N |P=0.040N* P=0.210N P=0.027N* P=0.092N | |POLY 1.5 | P=0.031N* P=0.349N P=0.182N P=0.070N |P=0.041N* P=0.209N P=0.028N* P=0.094N | |POLY 6 | P=0.033N* P=0.349N P=0.187N P=0.074N |P=0.038N* P=0.218N P=0.026N* P=0.090N | |LOGISTIC REGRESSION| P=0.034N* P=0.351N P=0.192N (e) |P=0.038N* P=0.209N P=0.030N* P=0.093N | |COCH-ARM / FISHERS | P=0.029N* P=0.339N P=0.168N P=0.059N |P=0.043N* P=0.218N P=0.027N* P=0.102N | |ORDER RESTRICTED | P=0.024N* (e) (e) (e) |P=0.011N* (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 46/48 (96%) 44/48 (92%) 41/50 (82%) 40/48 (83%) |13/49 (27%) 8/49 (16%) 11/50 (22%) 18/49 (37%) | |POLY-3 RATE (b) | 46/47.64 44/45.63 41/47.04 40/43.37 |13/42.72 8/43.99 11/44.22 18/44.17 | |POLY-3 PERCENT (g) | 96.6% 96.4% 87.2% 92.2% |30.4% 18.2% 24.9% 40.8% | |TERMINAL (d) | 39/39 (100%) 39/40 (98%) 34/38 (90%) 34/36 (94%) |11/33 (33%) 6/33 (18%) 11/39 (28%) 18/40 (45%) | |FIRST INCIDENCE | 515 603 493 558 |521 555 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.337N P=0.302N P=0.263N P=0.356N |P=0.188 P=0.159N P=0.244N P=0.400 | |POLY 3 | P=0.152N P=0.721N P=0.084N P=0.310N |P=0.068 P=0.138N P=0.367N P=0.216 | |POLY 1.5 | P=0.105N P=0.632N P=0.079N P=0.208N |P=0.068 P=0.143N P=0.378N P=0.211 | |POLY 6 | P=0.213N P=0.729 P=0.091N P=0.429N |P=0.071 P=0.141N P=0.359N P=0.220 | |LOGISTIC REGRESSION| P=0.153N P=0.565N P=0.088N P=0.259N |P=0.092 P=0.150N P=0.336N P=0.251 | |COCH-ARM / FISHERS | P=0.028N* P=0.339N P=0.030N* P=0.045N* |P=0.068 P=0.162N P=0.385N P=0.193 | |ORDER RESTRICTED | P=0.119N (e) (e) (e) |P=0.062 (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 | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/50 (0%) 0/48 (0%) |3/49 (6%) 1/49 (2%) 0/50 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 0/45.74 0/44.38 0/44.84 0/41.93 |3/43.32 1/43.30 0/44.22 2/44.99 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.9% 2.3% 0.0% 4.5% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |488 617 --- 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.424N P=0.295N P=0.113N P=0.469N | |POLY 3 | (e) (e) (e) (e) |P=0.439N P=0.305N P=0.115N P=0.483N | |POLY 1.5 | (e) (e) (e) (e) |P=0.442N P=0.303N P=0.116N P=0.488N | |POLY 6 | (e) (e) (e) (e) |P=0.434N P=0.312N P=0.114N P=0.476N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.469N P=0.324N P=0.112N P=0.553N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.443N P=0.309N P=0.117N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.174N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 0/50 (0%) 1/48 (2%) |0/49 (0%) 0/49 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/45.74 3/44.38 0/44.84 1/41.93 |0/41.96 0/42.91 0/44.22 0/44.17 | |POLY-3 PERCENT (g) | 4.4% 6.8% 0.0% 2.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/39 (5%) 3/40 (8%) 0/38 (0%) 1/36 (3%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.266N P=0.512 P=0.244N P=0.528N |(e) (e) (e) (e) | |POLY 3 | P=0.258N P=0.486 P=0.242N P=0.530N |(e) (e) (e) (e) | |POLY 1.5 | P=0.255N P=0.488 P=0.240N P=0.524N |(e) (e) (e) (e) | |POLY 6 | P=0.262N P=0.485 P=0.244N P=0.536N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.266N P=0.512 (e) P=0.528N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.239N P=0.500 P=0.237N P=0.500N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.203N (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 | | | | | |=================================================================================================================================| | | |Liver | | Angiectasis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 0/42.71 |1/42.68 2/43.91 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 653 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.165N P=0.500 P=0.467N P=0.462N | |POLY 3 | (e) (e) (e) (e) |P=0.180N P=0.510 P=0.493N P=0.489N | |POLY 1.5 | (e) (e) (e) (e) |P=0.183N P=0.508 P=0.497N P=0.492N | |POLY 6 | (e) (e) (e) (e) |P=0.177N P=0.507 P=0.489N P=0.485N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.182N P=0.506 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.188N P=0.500 P=0.500N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.163N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 2/49 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.83 1/46.01 1/44.84 2/42.71 |0/42.68 0/43.63 0/44.22 1/45.13 | |POLY-3 PERCENT (g) | 4.3% 2.2% 2.2% 4.7% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 2/39 (5%) 1/40 (3%) 1/38 (3%) 2/36 (6%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522 P=0.491N P=0.509N P=0.666 |P=0.224 (e) (e) P=0.538 | |POLY 3 | P=0.525 P=0.506N P=0.515N P=0.660 |P=0.206 (e) (e) P=0.511 | |POLY 1.5 | P=0.529 P=0.507N P=0.515N P=0.665 |P=0.203 (e) (e) P=0.508 | |POLY 6 | P=0.521 P=0.505N P=0.515N P=0.657 |P=0.209 (e) (e) P=0.515 | |LOGISTIC REGRESSION| P=0.522 P=0.491N P=0.509N P=0.666 |(e) (e) (e) P=0.538 | |COCH-ARM / FISHERS | P=0.548 P=0.500N P=0.500N P=0.684 |P=0.198 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.506 (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 | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 4/49 (8%) |6/50 (12%) 1/50 (2%) 6/50 (12%) 0/50 (0%) | |POLY-3 RATE (b) | 2/47.01 1/46.01 1/44.84 4/42.71 |6/42.72 1/43.63 6/44.22 0/45.13 | |POLY-3 PERCENT (g) | 4.3% 2.2% 2.2% 9.4% |14.1% 2.3% 13.6% 0.0% | |TERMINAL (d) | 1/39 (3%) 1/40 (3%) 1/38 (3%) 4/36 (11%) |5/33 (15%) 1/33 (3%) 6/39 (15%) 0/40 (0%) | |FIRST INCIDENCE | 682 729 (T) 729 (T) 729 (T) |720 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.137 P=0.497N P=0.514N P=0.297 |P=0.024N* P=0.060N P=0.502N P=0.010N* | |POLY 3 | P=0.144 P=0.507N P=0.516N P=0.294 |P=0.035N* P=0.052N P=0.597N P=0.012N* | |POLY 1.5 | P=0.147 P=0.507N P=0.515N P=0.300 |P=0.038N* P=0.052N P=0.609N P=0.013N* | |POLY 6 | P=0.141 P=0.508N P=0.518N P=0.288 |P=0.031N* P=0.053N P=0.584N P=0.011N* | |LOGISTIC REGRESSION| P=0.135 P=0.505N P=0.513N P=0.291 |P=0.025N* P=0.060N P=0.536N P=0.011N* | |COCH-ARM / FISHERS | P=0.158 P=0.500N P=0.500N P=0.329 |P=0.045N* P=0.056N P=0.620N P=0.013N* | |ORDER RESTRICTED | P=0.106 (e) (e) (e) |P=0.006N** (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 0/42.71 |0/42.68 2/44.15 0/44.22 1/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.5% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 625 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.569 P=0.239 (e) P=0.538 | |POLY 3 | (e) (e) (e) (e) |P=0.561 P=0.245 (e) P=0.511 | |POLY 1.5 | (e) (e) (e) (e) |P=0.554 P=0.243 (e) P=0.508 | |POLY 6 | (e) (e) (e) (e) |P=0.568 P=0.244 (e) P=0.515 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.539 P=0.234 (e) P=0.538 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.539 P=0.247 (e) P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.330 (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 | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 0/42.71 |0/42.68 1/43.63 2/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 2.3% 4.5% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 2/39 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.561N P=0.500 P=0.276 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.594N P=0.504 P=0.245 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.602N P=0.504 P=0.241 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.586N P=0.502 P=0.249 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.500 P=0.276 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.616N P=0.500 P=0.247 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.322N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 5/50 (10%) 5/50 (10%) 6/49 (12%) |16/50 (32%) 9/50 (18%) 10/50 (20%) 22/50 (44%) | |POLY-3 RATE (b) | 8/46.94 5/46.01 5/45.27 6/43.28 |16/43.97 9/46.01 10/45.06 22/45.62 | |POLY-3 PERCENT (g) | 17.0% 10.9% 11.0% 13.9% |36.4% 19.6% 22.2% 48.2% | |TERMINAL (d) | 7/39 (18%) 5/40 (13%) 3/38 (8%) 4/36 (11%) |12/33 (36%) 4/33 (12%) 8/39 (21%) 21/40 (53%) | |FIRST INCIDENCE | 702 729 (T) 653 642 |603 12 603 582 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.454N P=0.263N P=0.300N P=0.452N |P=0.139 P=0.095N P=0.069N P=0.358 | |POLY 3 | P=0.436N P=0.289N P=0.299N P=0.450N |P=0.039 * P=0.058N P=0.106N P=0.176 | |POLY 1.5 | P=0.432N P=0.289N P=0.301N P=0.445N |P=0.038 * P=0.061N P=0.115N P=0.171 | |POLY 6 | P=0.436N P=0.287N P=0.296N P=0.452N |P=0.040 * P=0.061N P=0.099N P=0.177 | |LOGISTIC REGRESSION| P=0.451N P=0.282N P=0.303N P=0.457N |P=0.048 * P=0.085N P=0.111N P=0.205 | |COCH-ARM / FISHERS | P=0.399N P=0.277N P=0.277N P=0.403N |P=0.043 * P=0.083N P=0.127N P=0.151 | |ORDER RESTRICTED | P=0.377N (e) (e) (e) |P=0.013 * (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: Hepatocyte | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 19/50 (38%) 17/50 (34%) 12/50 (24%) 8/49 (16%) |3/50 (6%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 19/46.83 17/46.01 12/44.84 8/42.71 |3/43.07 2/43.63 0/44.22 1/45.62 | |POLY-3 PERCENT (g) | 40.6% 37.0% 26.8% 18.7% |7.0% 4.6% 0.0% 2.2% | |TERMINAL (d) | 19/39 (49%) 17/40 (43%) 12/38 (32%) 8/36 (22%) |2/33 (6%) 2/33 (6%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |619 729 (T) --- 582 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.008N** P=0.372N P=0.098N P=0.016N* |P=0.134N P=0.498N P=0.104N P=0.269N | |POLY 3 | P=0.009N** P=0.442N P=0.118N P=0.019N* |P=0.157N P=0.494N P=0.114N P=0.285N | |POLY 1.5 | P=0.009N** P=0.445N P=0.119N P=0.018N* |P=0.160N P=0.493N P=0.116N P=0.291N | |POLY 6 | P=0.010N* P=0.436N P=0.116N P=0.020N* |P=0.153N P=0.503N P=0.111N P=0.278N | |LOGISTIC REGRESSION| P=0.008N** P=0.372N P=0.098N P=0.016N* |P=0.162N P=0.492N P=0.119N P=0.313N | |COCH-ARM / FISHERS | P=0.006N** P=0.418N P=0.097N P=0.014N* |P=0.163N P=0.500N P=0.121N P=0.309N | |ORDER RESTRICTED | P=0.016N* (e) (e) (e) |P=0.097N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 4/50 (8%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.83 0/46.01 0/44.84 0/42.71 |0/42.68 0/43.63 4/44.22 0/45.13 | |POLY-3 PERCENT (g) | 4.3% 0.0% 0.0% 0.0% |0.0% 0.0% 9.0% 0.0% | |TERMINAL (d) | 2/39 (5%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 4/39 (10%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.122N P=0.233N P=0.244N P=0.256N |P=0.564 (e) P=0.086 (e) | |POLY 3 | P=0.113N P=0.241N P=0.247N P=0.258N |P=0.536 (e) P=0.065 (e) | |POLY 1.5 | P=0.113N P=0.242N P=0.247N P=0.256N |P=0.524 (e) P=0.062 (e) | |POLY 6 | P=0.113N P=0.240N P=0.247N P=0.260N |P=0.553 (e) P=0.067 (e) | |LOGISTIC REGRESSION| P=0.122N (e) (e) (e) |(e) (e) P=0.086 (e) | |COCH-ARM / FISHERS | P=0.116N P=0.247N P=0.247N P=0.253N |P=0.500 (e) P=0.059 (e) | |ORDER RESTRICTED | P=0.037N* (e) (e) (e) |P=0.115 (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: Hepatocyte | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 2/49 (4%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 6/50 (12%) | |POLY-3 RATE (b) | 1/46.83 2/46.01 0/44.84 2/42.71 |2/42.96 0/43.63 1/44.22 6/45.62 | |POLY-3 PERCENT (g) | 2.1% 4.4% 0.0% 4.7% |4.7% 0.0% 2.3% 13.2% | |TERMINAL (d) | 1/39 (3%) 2/40 (5%) 0/38 (0%) 2/36 (6%) |1/33 (3%) 0/33 (0%) 1/39 (3%) 5/40 (13%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- 729 (T) |653 --- 729 (T) 582 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.438 P=0.509 P=0.505N P=0.472 |P=0.028 * P=0.240N P=0.459N P=0.192 | |POLY 3 | P=0.440 P=0.494 P=0.509N P=0.468 |P=0.016 * P=0.234N P=0.490N P=0.153 | |POLY 1.5 | P=0.443 P=0.493 P=0.508N P=0.472 |P=0.016 * P=0.233N P=0.495N P=0.147 | |POLY 6 | P=0.437 P=0.495 P=0.509N P=0.464 |P=0.018 * P=0.237N P=0.485N P=0.160 | |LOGISTIC REGRESSION| P=0.438 P=0.509 (e) P=0.472 |P=0.018 * P=0.235N P=0.493N P=0.143 | |COCH-ARM / FISHERS | P=0.462 P=0.500 P=0.500N P=0.492 |P=0.016 * P=0.247N P=0.500N P=0.134 | |ORDER RESTRICTED | P=0.371 (e) (e) (e) |P=0.012 * (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) 2/50 (4%) 7/49 (14%) |3/50 (6%) 3/50 (6%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 5/46.83 3/47.17 2/45.80 7/42.97 |3/42.86 3/44.19 1/44.22 1/45.13 | |POLY-3 PERCENT (g) | 10.7% 6.4% 4.4% 16.3% |7.0% 6.8% 2.3% 2.2% | |TERMINAL (d) | 5/39 (13%) 1/40 (3%) 0/38 (0%) 5/36 (14%) |2/33 (6%) 0/33 (0%) 1/39 (3%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 435 496 679 |681 653 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.195 P=0.350N P=0.233N P=0.322 |P=0.133N P=0.651 P=0.259N P=0.253N | |POLY 3 | P=0.196 P=0.353N P=0.225N P=0.320 |P=0.155N P=0.648N P=0.294N P=0.287N | |POLY 1.5 | P=0.201 P=0.359N P=0.229N P=0.326 |P=0.159N P=0.651N P=0.300N P=0.292N | |POLY 6 | P=0.193 P=0.346N P=0.221N P=0.317 |P=0.151N P=0.651N P=0.288N P=0.281N | |LOGISTIC REGRESSION| P=0.230 P=0.324N P=0.201N P=0.307 |P=0.156N P=0.657N P=0.288N P=0.281N | |COCH-ARM / FISHERS | P=0.222 P=0.357N P=0.218N P=0.365 |P=0.165N P=0.661N P=0.309N P=0.309N | |ORDER RESTRICTED | P=0.106 (e) (e) (e) |P=0.223N (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: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 18/50 (36%) 17/50 (34%) 17/50 (34%) 18/49 (37%) |5/50 (10%) 3/50 (6%) 1/50 (2%) 5/50 (10%) | |POLY-3 RATE (b) | 18/46.83 17/46.60 17/44.90 18/42.71 |5/43.04 3/44.10 1/44.22 5/46.58 | |POLY-3 PERCENT (g) | 38.4% 36.5% 37.9% 42.1% |11.6% 6.8% 2.3% 10.7% | |TERMINAL (d) | 18/39 (46%) 16/40 (40%) 16/38 (42%) 18/36 (50%) |3/33 (9%) 2/33 (6%) 1/39 (3%) 2/40 (5%) | |FIRST INCIDENCE | 729 (T) 545 715 729 (T) |681 588 729 (T) 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.370 P=0.462N P=0.541N P=0.460 |P=0.529N P=0.359N P=0.079N P=0.549N | |POLY 3 | P=0.371 P=0.507N P=0.563N P=0.444 |P=0.567 P=0.343N P=0.095N P=0.580N | |POLY 1.5 | P=0.393 P=0.517N P=0.561N P=0.462 |P=0.555 P=0.344N P=0.098N P=0.597N | |POLY 6 | P=0.351 P=0.494N P=0.563N P=0.427 |P=0.573N P=0.350N P=0.092N P=0.561N | |LOGISTIC REGRESSION| P=0.346 P=0.520N P=0.577N P=0.460 |P=0.537 P=0.347N P=0.094N P=0.625 | |COCH-ARM / FISHERS | P=0.488 P=0.500N P=0.500N P=0.553 |P=0.537 P=0.357N P=0.102N P=0.630N | |ORDER RESTRICTED | P=0.512 (e) (e) (e) |P=0.299N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/46.92 0/46.01 1/45.29 0/43.48 |2/43.53 0/43.63 1/45.22 1/46.12 | |POLY-3 PERCENT (g) | 2.1% 0.0% 2.2% 0.0% |4.6% 0.0% 2.2% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 706 --- 597 --- |506 --- 15 105 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.424N P=0.505N P=0.753 P=0.520N |P=0.491N P=0.236N P=0.492N P=0.487N | |POLY 3 | P=0.415N P=0.504N P=0.753 P=0.515N |P=0.490N P=0.236N P=0.487N P=0.480N | |POLY 1.5 | P=0.413N P=0.504N P=0.752 P=0.512N |P=0.493N P=0.235N P=0.490N P=0.484N | |POLY 6 | P=0.417N P=0.504N P=0.753 P=0.518N |P=0.482N P=0.242N P=0.483N P=0.476N | |LOGISTIC REGRESSION| P=0.383N P=0.501N P=0.743N P=0.509N |P=0.576N P=0.247N P=0.456N P=0.605N | |COCH-ARM / FISHERS | P=0.405N P=0.500N P=0.753N P=0.500N |P=0.500N P=0.247N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.267N (e) (e) (e) |P=0.254N (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 | | | | | |=================================================================================================================================| | | |Lung | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 4/50 (8%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 1/46.83 1/46.01 4/44.84 0/43.48 |0/42.68 1/43.91 0/44.22 1/45.13 | |POLY-3 PERCENT (g) | 2.1% 2.2% 8.9% 0.0% |0.0% 2.3% 0.0% 2.2% | |TERMINAL (d) | 1/39 (3%) 1/40 (3%) 4/38 (11%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |--- 653 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478N P=0.756N P=0.171 P=0.516N |P=0.431 P=0.500 (e) P=0.538 | |POLY 3 | P=0.484N P=0.757 P=0.166 P=0.515N |P=0.421 P=0.506 (e) P=0.511 | |POLY 1.5 | P=0.476N P=0.756 P=0.167 P=0.512N |P=0.416 P=0.505 (e) P=0.508 | |POLY 6 | P=0.493N P=0.757 P=0.165 P=0.517N |P=0.427 P=0.504 (e) P=0.515 | |LOGISTIC REGRESSION| P=0.478N P=0.756N P=0.171 (e) |P=0.407 P=0.496 (e) P=0.538 | |COCH-ARM / FISHERS | P=0.444N P=0.753N P=0.181 P=0.500N |P=0.405 P=0.500 (e) P=0.500 | |ORDER RESTRICTED | P=0.191N (e) (e) (e) |P=0.261 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Infiltration Cellular Polymorphonuclear | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 0/43.48 |0/42.68 2/43.80 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 683 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.376N P=0.240 (e) (e) | |POLY 3 | (e) (e) (e) (e) |P=0.390N P=0.243 (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.394N P=0.242 (e) (e) | |POLY 6 | (e) (e) (e) (e) |P=0.387N P=0.241 (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.397N P=0.241 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.405N P=0.247 (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.241N (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 | | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 1/50 (2%) 3/50 (6%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 4/46.83 2/46.01 1/44.84 3/43.48 |1/43.38 2/43.63 1/44.22 2/45.13 | |POLY-3 PERCENT (g) | 8.5% 4.4% 2.2% 6.9% |2.3% 4.6% 2.3% 4.4% | |TERMINAL (d) | 4/39 (10%) 2/40 (5%) 1/38 (3%) 3/36 (8%) |0/33 (0%) 2/33 (6%) 1/39 (3%) 2/40 (5%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |488 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.501N P=0.325N P=0.187N P=0.544N |P=0.511 P=0.505 P=0.742N P=0.547 | |POLY 3 | P=0.477N P=0.345N P=0.192N P=0.540N |P=0.461 P=0.502 P=0.756N P=0.514 | |POLY 1.5 | P=0.473N P=0.346N P=0.192N P=0.533N |P=0.456 P=0.504 P=0.759N P=0.510 | |POLY 6 | P=0.481N P=0.344N P=0.192N P=0.548N |P=0.468 P=0.495 P=0.754N P=0.519 | |LOGISTIC REGRESSION| P=0.501N P=0.325N P=0.187N P=0.544N |P=0.448 P=0.493 P=0.762N P=0.484 | |COCH-ARM / FISHERS | P=0.456N P=0.339N P=0.181N P=0.500N |P=0.444 P=0.500 P=0.753N P=0.500 | |ORDER RESTRICTED | P=0.317N (e) (e) (e) |P=0.460 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Mediastinum | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.83 0/46.01 0/44.84 0/43.48 |0/42.68 2/43.63 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 2.1% 0.0% 0.0% 0.0% |0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 2/33 (6%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.316N P=0.495N P=0.505N P=0.516N |P=0.363N P=0.238 (e) (e) | |POLY 3 | P=0.299N P=0.504N P=0.509N P=0.515N |P=0.391N P=0.242 (e) (e) | |POLY 1.5 | P=0.300N P=0.504N P=0.508N P=0.512N |P=0.394N P=0.242 (e) (e) | |POLY 6 | P=0.298N P=0.503N P=0.509N P=0.517N |P=0.388N P=0.239 (e) (e) | |LOGISTIC REGRESSION| P=0.316N (e) (e) (e) |(e) P=0.238 (e) (e) | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.405N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.134N (e) (e) (e) |P=0.241N (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 | | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 1/48 (2%) 0/47 (0%) 1/47 (2%) |6/47 (13%) 4/49 (8%) 2/49 (4%) 1/48 (2%) | |POLY-3 RATE (b) | 0/44.40 1/44.16 0/42.29 1/40.67 |6/40.17 4/43.97 2/43.67 1/43.13 | |POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 2.5% |14.9% 9.1% 4.6% 2.3% | |TERMINAL (d) | 0/38 (0%) 1/39 (3%) 0/36 (0%) 1/34 (3%) |4/30 (13%) 2/33 (6%) 1/39 (3%) 1/38 (3%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |603 555 653 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.378 P=0.505 (e) P=0.478 |P=0.018N* P=0.334N P=0.089N P=0.035N* | |POLY 3 | P=0.380 P=0.499 (e) P=0.483 |P=0.024N* P=0.313N P=0.106N P=0.044N* | |POLY 1.5 | P=0.384 P=0.499 (e) P=0.486 |P=0.025N* P=0.321N P=0.113N P=0.047N* | |POLY 6 | P=0.375 P=0.499 (e) P=0.479 |P=0.023N* P=0.312N P=0.100N P=0.042N* | |LOGISTIC REGRESSION| (e) P=0.505 (e) P=0.478 |P=0.027N* P=0.339N P=0.112N P=0.046N* | |COCH-ARM / FISHERS | P=0.403 P=0.505 (e) P=0.500 |P=0.027N* P=0.344N P=0.121N P=0.052N | |ORDER RESTRICTED | P=0.235 (e) (e) (e) |P=0.021N* (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/48 (0%) 1/49 (2%) 0/48 (0%) |1/47 (2%) 1/48 (2%) 5/49 (10%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.83 0/44.12 1/44.57 0/41.62 |1/39.89 1/42.00 5/43.71 2/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |2.5% 2.4% 11.4% 4.4% | |TERMINAL (d) | 0/39 (0%) 0/39 (0%) 0/38 (0%) 0/36 (0%) |1/32 (3%) 0/32 (0%) 5/39 (13%) 2/40 (5%) | |FIRST INCIDENCE | --- --- 653 --- |729 (T) 707 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.686 (e) P=0.496 (e) |P=0.406 P=0.757 P=0.153 P=0.578 | |POLY 3 | P=0.659 (e) P=0.490 (e) |P=0.361 P=0.749N P=0.123 P=0.543 | |POLY 1.5 | P=0.666 (e) P=0.489 (e) |P=0.349 P=0.750N P=0.117 P=0.536 | |POLY 6 | P=0.652 (e) P=0.492 (e) |P=0.376 P=0.752N P=0.129 P=0.550 | |LOGISTIC REGRESSION| P=0.706 (e) P=0.520 (e) |P=0.384 P=0.756N P=0.153 P=0.578 | |COCH-ARM / FISHERS | P=0.691 (e) P=0.495 (e) |P=0.327 P=0.747N P=0.112 P=0.523 | |ORDER RESTRICTED | P=0.373 (e) (e) (e) |P=0.207 (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 | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/48 (2%) 3/49 (6%) 0/48 (0%) |0/47 (0%) 0/48 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/46.97 1/44.12 3/44.54 0/41.62 |0/39.89 0/41.91 0/43.71 1/45.13 | |POLY-3 PERCENT (g) | 6.4% 2.3% 6.7% 0.0% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 1/39 (3%) 1/39 (3%) 1/38 (3%) 0/36 (0%) |0/32 (0%) 0/32 (0%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | 702 729 (T) 681 --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.160N P=0.314N P=0.638 P=0.145N |P=0.228 (e) (e) P=0.545 | |POLY 3 | P=0.159N P=0.328N P=0.638 P=0.142N |P=0.213 (e) (e) P=0.525 | |POLY 1.5 | P=0.155N P=0.328N P=0.636 P=0.139N |P=0.211 (e) (e) P=0.521 | |POLY 6 | P=0.163N P=0.328N P=0.641 P=0.145N |P=0.217 (e) (e) P=0.528 | |LOGISTIC REGRESSION| P=0.154N P=0.325N P=0.640 P=0.142N |(e) (e) (e) P=0.545 | |COCH-ARM / FISHERS | P=0.141N P=0.324N P=0.651 P=0.129N |P=0.205 (e) (e) P=0.515 | |ORDER RESTRICTED | P=0.094N (e) (e) (e) |P=0.144 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/48 (4%) 4/49 (8%) 2/48 (4%) |3/47 (6%) 6/48 (13%) 2/49 (4%) 5/50 (10%) | |POLY-3 RATE (b) | 3/46.83 2/44.12 4/44.72 2/41.62 |3/40.33 6/42.88 2/43.71 5/45.13 | |POLY-3 PERCENT (g) | 6.4% 4.5% 8.9% 4.8% |7.4% 14.0% 4.6% 11.1% | |TERMINAL (d) | 3/39 (8%) 2/39 (5%) 2/38 (5%) 2/36 (6%) |2/32 (6%) 3/32 (9%) 2/39 (5%) 5/40 (13%) | |FIRST INCIDENCE | 729 (T) 729 (T) 653 729 (T) |603 555 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.523N P=0.500N P=0.485 P=0.537N |P=0.553 P=0.249 P=0.429N P=0.469 | |POLY 3 | P=0.533N P=0.527N P=0.475 P=0.553N |P=0.497 P=0.272 P=0.463N P=0.419 | |POLY 1.5 | P=0.526N P=0.528N P=0.471 P=0.547N |P=0.488 P=0.268 P=0.472N P=0.412 | |POLY 6 | P=0.540N P=0.525N P=0.482 P=0.559N |P=0.506 P=0.270 P=0.455N P=0.426 | |LOGISTIC REGRESSION| P=0.534N P=0.500N P=0.473 P=0.537N |P=0.489 P=0.255 P=0.468N P=0.425 | |COCH-ARM / FISHERS | P=0.494N P=0.520N P=0.489 P=0.520N |P=0.467 P=0.254 P=0.480N P=0.393 | |ORDER RESTRICTED | P=0.567N (e) (e) (e) |P=0.447 (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 | | | | | |=================================================================================================================================| | | |Lymph Node: Iliac | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/6 (0%) 0/5 (0%) 0/5 (0%) 0/4 (0%) |0/11 (0%) 1/13 (8%) 1/10 (10%) 3/10 (30%) | |POLY-3 RATE (b) | 0/5.50 0/5.00 0/5.00 0/3.13 |0/8.74 1/10.61 1/8.86 3/9.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 9.4% 11.3% 31.5% | |TERMINAL (d) | 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/1 (0%) |0/5 (0%) 0/5 (0%) 1/7 (14%) 3/8 (38%) | |FIRST INCIDENCE | --- --- --- --- |--- 707 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.106 P=0.494 P=0.567 P=0.198 | |POLY 3 | (e) (e) (e) (e) |P=0.042 * P=0.539 P=0.503 P=0.109 | |POLY 1.5 | (e) (e) (e) (e) |P=0.035 * P=0.538 P=0.494 P=0.096 | |POLY 6 | (e) (e) (e) (e) |P=0.053 P=0.534 P=0.513 P=0.129 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.085 P=0.524 P=0.567 P=0.198 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.030 * P=0.542 P=0.476 P=0.090 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.034 * (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Lymph Node: Iliac | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/6 (0%) 0/5 (0%) 0/5 (0%) 0/4 (0%) |2/11 (18%) 0/13 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/5.50 0/5.00 0/5.00 0/3.13 |2/9.44 0/10.52 0/8.86 0/9.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |21.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/1 (0%) |1/5 (20%) 0/5 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |488 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.093N P=0.235N P=0.203N P=0.187N | |POLY 3 | (e) (e) (e) (e) |P=0.111N P=0.199N P=0.239N P=0.223N | |POLY 1.5 | (e) (e) (e) (e) |P=0.114N P=0.194N P=0.244N P=0.234N | |POLY 6 | (e) (e) (e) (e) |P=0.104N P=0.213N P=0.233N P=0.208N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.201N P=0.246N P=0.340N P=0.440N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.123N P=0.199N P=0.262N P=0.262N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.022N* (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 | | | | | |=================================================================================================================================| | | |Lymph Node: Iliac | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/6 (0%) 0/5 (0%) 0/5 (0%) 1/4 (25%) |2/11 (18%) 2/13 (15%) 2/10 (20%) 2/10 (20%) | |POLY-3 RATE (b) | 0/5.50 0/5.00 0/5.00 1/3.68 |2/8.79 2/10.67 2/9.29 2/9.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 27.2% |22.8% 18.7% 21.5% 21.0% | |TERMINAL (d) | 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/1 (0%) |1/5 (20%) 1/5 (20%) 1/7 (14%) 2/8 (25%) | |FIRST INCIDENCE | --- --- --- 558 |715 690 603 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.194 (e) (e) P=0.491 |P=0.436N P=0.686 P=0.622N P=0.550N | |POLY 3 | P=0.144 (e) (e) P=0.416 |P=0.606N P=0.632N P=0.686N P=0.676N | |POLY 1.5 | P=0.146 (e) (e) P=0.416 |P=0.579 P=0.631N P=0.702 P=0.702N | |POLY 6 | P=0.141 (e) (e) P=0.417 |P=0.563N P=0.646N P=0.657N P=0.641N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.570N P=0.698N P=0.707 P=0.584N | |COCH-ARM / FISHERS | P=0.149 (e) (e) P=0.400 |P=0.529 P=0.637N P=0.669 P=0.669 | |ORDER RESTRICTED | P=0.066 (e) (e) (e) |P=0.691N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Lymph Node: Inguinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/6 (33%) 3/5 (60%) 4/5 (80%) 1/4 (25%) |1/11 (9%) 0/13 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/5.78 3/5.00 4/5.00 1/3.68 |1/8.74 0/10.52 0/8.86 0/9.52 | |POLY-3 PERCENT (g) | 34.6% 60.0% 80.0% 27.2% |11.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/3 (0%) 3/5 (60%) 4/5 (80%) 0/1 (0%) |1/5 (20%) 0/5 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 682 729 (T) 729 (T) 558 |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.573 P=0.637 P=0.486 P=0.534N |P=0.245N P=0.500N P=0.433N P=0.406N | |POLY 3 | P=0.600N P=0.417 P=0.182 P=0.667N |P=0.339N P=0.462N P=0.497N P=0.483N | |POLY 1.5 | P=0.581N P=0.408 P=0.175 P=0.658N |P=0.334N P=0.462N P=0.506N P=0.498N | |POLY 6 | P=0.597 P=0.433 P=0.195 P=0.683N |P=0.342N P=0.469N P=0.486N P=0.463N | |LOGISTIC REGRESSION| P=0.478N P=0.275 P=0.124 P=0.346N |P=0.245N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.562N P=0.392 P=0.175 P=0.667N |P=0.322N P=0.458N P=0.524N P=0.524N | |ORDER RESTRICTED | P=0.319N (e) (e) (e) |P=0.104N (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 | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/6 (0%) 0/5 (0%) 1/5 (20%) 0/4 (0%) |1/11 (9%) 2/13 (15%) 1/10 (10%) 3/10 (30%) | |POLY-3 RATE (b) | 0/5.50 0/5.00 1/5.00 0/3.13 |1/8.74 2/10.52 1/9.29 3/9.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 20.0% 0.0% |11.5% 19.0% 10.8% 31.5% | |TERMINAL (d) | 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/1 (0%) |1/5 (20%) 2/5 (40%) 0/7 (0%) 3/8 (38%) | |FIRST INCIDENCE | --- --- 729 (T) --- |729 (T) 729 (T) 603 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.634 (e) P=0.602 (e) |P=0.392 P=0.500 P=0.721N P=0.482 | |POLY 3 | P=0.545 (e) P=0.481 (e) |P=0.225 P=0.568 P=0.749N P=0.322 | |POLY 1.5 | P=0.594 (e) P=0.472 (e) |P=0.201 P=0.567 P=0.761 P=0.293 | |POLY 6 | P=0.468 (e) P=0.497 (e) |P=0.262 P=0.556 P=0.730N P=0.362 | |LOGISTIC REGRESSION| (e) (e) P=0.602 (e) |P=0.261 P=0.500 P=0.739 P=0.482 | |COCH-ARM / FISHERS | P=0.653 (e) P=0.455 (e) |P=0.167 P=0.565 P=0.738 P=0.256 | |ORDER RESTRICTED | P=0.397 (e) (e) (e) |P=0.225 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/6 (0%) 0/5 (0%) 0/5 (0%) 0/4 (0%) |1/11 (9%) 1/13 (8%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 0/5.50 0/5.00 0/5.00 0/3.13 |1/9.02 1/10.52 2/8.86 0/9.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |11.1% 9.5% 22.6% 0.0% | |TERMINAL (d) | 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/1 (0%) |0/5 (0%) 1/5 (20%) 2/7 (29%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |653 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.255N P=0.760 P=0.588 P=0.485N | |POLY 3 | (e) (e) (e) (e) |P=0.349N P=0.730N P=0.493 P=0.489N | |POLY 1.5 | (e) (e) (e) (e) |P=0.376N P=0.724N P=0.483 P=0.501N | |POLY 6 | (e) (e) (e) (e) |P=0.315N P=0.747N P=0.502 P=0.476N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.321N P=0.730N P=0.510 P=0.600N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.409N P=0.717N P=0.462 P=0.524N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.265N (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 | | | | | |=================================================================================================================================| | | |Mesentery | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |3/23 (13%) 5/20 (25%) 0/14 (0%) 1/18 (6%) | |POLY-3 RATE (b) | 0/45.83 1/45.09 0/44.84 1/43.48 |3/19.63 5/18.04 0/12.80 1/16.08 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 2.3% |15.3% 27.7% 0.0% 6.2% | |TERMINAL (d) | 0/38 (0%) 1/40 (3%) 0/38 (0%) 1/36 (3%) |3/15 (20%) 3/12 (25%) 0/11 (0%) 1/13 (8%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |729 (T) 683 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.389 P=0.510 (e) P=0.489 |P=0.105N P=0.258 P=0.174N P=0.352N | |POLY 3 | P=0.390 P=0.497 (e) P=0.490 |P=0.129N P=0.297 P=0.195N P=0.375N | |POLY 1.5 | P=0.393 P=0.496 (e) P=0.492 |P=0.135N P=0.291 P=0.201N P=0.380N | |POLY 6 | P=0.387 P=0.498 (e) P=0.487 |P=0.126N P=0.295 P=0.190N P=0.374N | |LOGISTIC REGRESSION| (e) P=0.510 (e) P=0.489 |P=0.132N P=0.263 (e) P=0.352N | |COCH-ARM / FISHERS | P=0.410 P=0.500 (e) P=0.505 |P=0.151N P=0.270 P=0.228N P=0.402N | |ORDER RESTRICTED | P=0.241 (e) (e) (e) |P=0.081N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 2/49 (4%) 4/50 (8%) 4/50 (8%) |17/23 (74%) 13/20 (65%) 9/14 (64%) 15/18 (83%) | |POLY-3 RATE (b) | 4/46.14 2/45.09 4/44.84 4/43.72 |17/21.33 13/18.51 9/12.80 15/17.52 | |POLY-3 PERCENT (g) | 8.7% 4.4% 8.9% 9.2% |79.7% 70.2% 70.3% 85.6% | |TERMINAL (d) | 2/38 (5%) 2/40 (5%) 4/38 (11%) 3/36 (8%) |12/15 (80%) 9/12 (75%) 9/11 (82%) 12/13 (92%) | |FIRST INCIDENCE | 672 729 (T) 729 (T) 664 |488 653 729 (T) 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.419 P=0.329N P=0.634 P=0.602 |P=0.478N P=0.430N P=0.100N P=0.554N | |POLY 3 | P=0.435 P=0.348N P=0.627 P=0.613 |P=0.336 P=0.369N P=0.415N P=0.476 | |POLY 1.5 | P=0.443 P=0.348N P=0.630 P=0.621 |P=0.315 P=0.357N P=0.393N P=0.444 | |POLY 6 | P=0.427 P=0.348N P=0.624 P=0.606 |P=0.350 P=0.425N P=0.475N P=0.488 | |LOGISTIC REGRESSION| P=0.431 P=0.344N P=0.633 P=0.624 |P=0.339 P=0.278N P=0.275N P=0.443 | |COCH-ARM / FISHERS | P=0.476 P=0.339N P=0.631N P=0.631N |P=0.270 P=0.381N P=0.397N P=0.370 | |ORDER RESTRICTED | P=0.512 (e) (e) (e) |P=0.282 (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 | | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/45.84 0/46.01 1/44.84 0/43.48 |0/42.68 0/43.63 1/43.54 0/45.13 | |POLY-3 PERCENT (g) | 4.4% 0.0% 2.2% 0.0% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 1/38 (3%) 0/40 (0%) 1/38 (3%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 725 --- 729 (T) --- |--- --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.201N P=0.234N P=0.506N P=0.257N |P=0.708 (e) P=0.516 (e) | |POLY 3 | P=0.191N P=0.236N P=0.508N P=0.249N |P=0.713 (e) P=0.504 (e) | |POLY 1.5 | P=0.190N P=0.237N P=0.507N P=0.246N |P=0.706 (e) P=0.500 (e) | |POLY 6 | P=0.193N P=0.235N P=0.508N P=0.252N |P=0.721 (e) P=0.509 (e) | |LOGISTIC REGRESSION| P=0.201N P=0.234N P=0.509N P=0.255N |P=0.695 (e) P=0.497 (e) | |COCH-ARM / FISHERS | P=0.185N P=0.242N P=0.492N P=0.242N |P=0.694 (e) P=0.495 (e) | |ORDER RESTRICTED | P=0.082N (e) (e) (e) |P=0.384 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/45.83 2/46.01 1/44.84 0/43.48 |0/42.68 0/43.63 0/43.39 0/45.13 | |POLY-3 PERCENT (g) | 2.2% 4.4% 2.2% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/38 (3%) 2/40 (5%) 1/38 (3%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.262N P=0.518 P=0.762 P=0.511N |(e) (e) (e) (e) | |POLY 3 | P=0.263N P=0.501 P=0.756 P=0.510N |(e) (e) (e) (e) | |POLY 1.5 | P=0.260N P=0.501 P=0.756 P=0.508N |(e) (e) (e) (e) | |POLY 6 | P=0.266N P=0.503 P=0.756 P=0.513N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.262N P=0.518 P=0.762 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.243N P=0.508 P=0.747N P=0.495N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.237N (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 | | | | | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 2/50 (4%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 1/45.83 0/46.01 2/45.29 3/43.92 |1/43.38 0/43.63 1/43.79 0/45.13 | |POLY-3 PERCENT (g) | 2.2% 0.0% 4.4% 6.8% |2.3% 0.0% 2.3% 0.0% | |TERMINAL (d) | 1/38 (3%) 0/40 (0%) 1/38 (3%) 1/36 (3%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- 597 664 |488 --- 614 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.091 P=0.490N P=0.498 P=0.282 |P=0.401N P=0.492N P=0.758N P=0.496N | |POLY 3 | P=0.096 P=0.499N P=0.496 P=0.290 |P=0.400N P=0.499N P=0.759N P=0.492N | |POLY 1.5 | P=0.097 P=0.500N P=0.495 P=0.293 |P=0.403N P=0.498N P=0.759 P=0.494N | |POLY 6 | P=0.095 P=0.498N P=0.498 P=0.289 |P=0.395N P=0.503N P=0.754N P=0.489N | |LOGISTIC REGRESSION| P=0.106 (e) P=0.517 P=0.301 |P=0.425N P=0.516N P=0.763N P=0.545N | |COCH-ARM / FISHERS | P=0.106 P=0.495N P=0.508 P=0.316 |P=0.406N P=0.500N P=0.747 P=0.500N | |ORDER RESTRICTED | P=0.099 (e) (e) (e) |P=0.243N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/49 (4%) 3/50 (6%) 1/49 (2%) 1/49 (2%) | |POLY-3 RATE (b) | |2/41.68 3/43.91 1/43.71 1/44.17 | |POLY-3 PERCENT (g) | |4.8% 6.8% 2.3% 2.3% | |TERMINAL (d) | |2/32 (6%) 2/33 (6%) 1/39 (3%) 1/40 (3%) | |FIRST INCIDENCE | |729 (T) 653 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.215N P=0.511 P=0.431N P=0.422N | |POLY 3 | |P=0.264N P=0.524 P=0.483N P=0.480N | |POLY 1.5 | |P=0.271N P=0.521 P=0.492N P=0.486N | |POLY 6 | |P=0.257N P=0.521 P=0.474N P=0.472N | |LOGISTIC REGRESSION| |P=0.255N P=0.517 P=0.431N P=0.422N | |COCH-ARM / FISHERS | |P=0.281N P=0.510 P=0.500N P=0.500N | |ORDER RESTRICTED | |P=0.320N (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 | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |14/49 (29%) 16/50 (32%) 14/49 (29%) 18/49 (37%) | |POLY-3 RATE (b) | |14/42.50 16/45.16 14/44.02 18/45.05 | |POLY-3 PERCENT (g) | |32.9% 35.4% 31.8% 40.0% | |TERMINAL (d) | |12/32 (38%) 12/33 (36%) 12/39 (31%) 16/40 (40%) | |FIRST INCIDENCE | |603 540 687 582 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.526 P=0.454 P=0.372N P=0.515 | |POLY 3 | |P=0.293 P=0.492 P=0.546N P=0.323 | |POLY 1.5 | |P=0.275 P=0.480 P=0.569N P=0.302 | |POLY 6 | |P=0.321 P=0.489 P=0.522N P=0.347 | |LOGISTIC REGRESSION| |P=0.302 P=0.469 P=0.514N P=0.324 | |COCH-ARM / FISHERS | |P=0.242 P=0.440 P=0.588N P=0.259 | |ORDER RESTRICTED | |P=0.392 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/49 (4%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 RATE (b) | |2/41.68 0/43.63 0/43.71 0/44.17 | |POLY-3 PERCENT (g) | |4.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | |2/32 (6%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.094N P=0.231N P=0.196N P=0.191N | |POLY 3 | |P=0.116N P=0.227N P=0.227N P=0.224N | |POLY 1.5 | |P=0.116N P=0.227N P=0.232N P=0.228N | |POLY 6 | |P=0.115N P=0.229N P=0.221N P=0.220N | |LOGISTIC REGRESSION| |P=0.094N (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.115N P=0.242N P=0.247N P=0.247N | |ORDER RESTRICTED | |P=0.025N* (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 | | | | | |=================================================================================================================================| | | |Ovary | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/49 (6%) 2/50 (4%) 0/49 (0%) 3/49 (6%) | |POLY-3 RATE (b) | |3/41.68 2/43.78 0/43.71 3/44.17 | |POLY-3 PERCENT (g) | |7.2% 4.6% 0.0% 6.8% | |TERMINAL (d) | |3/32 (9%) 1/33 (3%) 0/39 (0%) 3/40 (8%) | |FIRST INCIDENCE | |729 (T) 690 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.501N P=0.491N P=0.088N P=0.556N | |POLY 3 | |P=0.590N P=0.478N P=0.110N P=0.636N | |POLY 1.5 | |P=0.594N P=0.479N P=0.114N P=0.644N | |POLY 6 | |P=0.583N P=0.481N P=0.105N P=0.626N | |LOGISTIC REGRESSION| |P=0.550N P=0.491N (e) P=0.556N | |COCH-ARM / FISHERS | |P=0.594 P=0.490N P=0.121N P=0.661N | |ORDER RESTRICTED | |P=0.322N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/49 (4%) 1/50 (2%) 1/49 (2%) 0/49 (0%) | |POLY-3 RATE (b) | |2/41.68 1/43.63 1/43.71 0/44.17 | |POLY-3 PERCENT (g) | |4.8% 2.3% 2.3% 0.0% | |TERMINAL (d) | |2/32 (6%) 1/33 (3%) 1/39 (3%) 0/40 (0%) | |FIRST INCIDENCE | |729 (T) 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.116N P=0.489N P=0.431N P=0.191N | |POLY 3 | |P=0.147N P=0.484N P=0.483N P=0.224N | |POLY 1.5 | |P=0.150N P=0.485N P=0.492N P=0.228N | |POLY 6 | |P=0.143N P=0.488N P=0.474N P=0.220N | |LOGISTIC REGRESSION| |P=0.116N P=0.489N P=0.431N (e) | |COCH-ARM / FISHERS | |P=0.154N P=0.492N P=0.500N P=0.247N | |ORDER RESTRICTED | |P=0.108N (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 | | | | | |=================================================================================================================================| | | |Oviduct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/3 (100%) 0/1 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | |3/3.00 0/0.47 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | |100.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | |3/3 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=1.000 P=1.000N (e) (e) | |POLY 3 | |(e) P=0.250 (e) (e) | |POLY 1.5 | |(e) P=0.250 (e) (e) | |POLY 6 | |(e) P=0.250 (e) (e) | |LOGISTIC REGRESSION| |P=1.000 (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.748N P=0.250N (e) (e) | |ORDER RESTRICTED | |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Acinus | | Atrophy Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) |0/50 (0%) 2/48 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.29 0/42.69 |0/42.68 2/42.26 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.7% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 684 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.373N P=0.240 (e) (e) | |POLY 3 | (e) (e) (e) (e) |P=0.387N P=0.235 (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.391N P=0.234 (e) (e) | |POLY 6 | (e) (e) (e) (e) |P=0.383N P=0.234 (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.395N P=0.233 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.403N P=0.237 (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.235N (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 | | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 3/49 (6%) |1/50 (2%) 2/48 (4%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.29 3/42.93 |1/42.68 2/42.09 1/44.66 3/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.0% |2.3% 4.8% 2.2% 6.7% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 2/36 (6%) |1/33 (3%) 2/33 (6%) 0/39 (0%) 3/40 (8%) | |FIRST INCIDENCE | --- --- --- 664 |729 (T) 729 (T) 603 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * (e) (e) P=0.110 |P=0.301 P=0.500 P=0.742N P=0.376 | |POLY 3 | P=0.010 * (e) (e) P=0.106 |P=0.260 P=0.495 P=0.751N P=0.325 | |POLY 1.5 | P=0.010 * (e) (e) P=0.108 |P=0.255 P=0.494 P=0.756N P=0.319 | |POLY 6 | P=0.010 * (e) (e) P=0.104 |P=0.268 P=0.493 P=0.745N P=0.333 | |LOGISTIC REGRESSION| P=0.010 * (e) (e) P=0.111 |P=0.257 P=0.500 P=0.762 P=0.376 | |COCH-ARM / FISHERS | P=0.012 * (e) (e) P=0.121 |P=0.242 P=0.485 P=0.753N P=0.309 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) |P=0.242 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Duct | | Cyst Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) |0/50 (0%) 2/48 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.29 0/42.69 |0/42.68 2/42.26 0/44.22 1/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.7% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 684 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.585 P=0.240 (e) P=0.538 | |POLY 3 | (e) (e) (e) (e) |P=0.564 P=0.235 (e) P=0.511 | |POLY 1.5 | (e) (e) (e) (e) |P=0.557 P=0.234 (e) P=0.508 | |POLY 6 | (e) (e) (e) (e) |P=0.571 P=0.234 (e) P=0.515 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.557 P=0.233 (e) P=0.538 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.543 P=0.237 (e) P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.325 (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 | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 2/46 (4%) 1/47 (2%) |2/46 (4%) 2/43 (5%) 0/49 (0%) 1/49 (2%) | |POLY-3 RATE (b) | 1/45.83 0/46.01 2/41.18 1/41.95 |2/40.35 2/37.56 0/43.22 1/44.13 | |POLY-3 PERCENT (g) | 2.2% 0.0% 4.9% 2.4% |5.0% 5.3% 0.0% 2.3% | |TERMINAL (d) | 1/38 (3%) 0/40 (0%) 1/35 (3%) 0/36 (0%) |2/31 (7%) 2/29 (7%) 0/38 (0%) 1/39 (3%) | |FIRST INCIDENCE | 729 (T) --- 653 498 |729 (T) 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.476 P=0.490N P=0.478 P=0.745 |P=0.222N P=0.672 P=0.195N P=0.420N | |POLY 3 | P=0.466 P=0.499N P=0.463 P=0.741 |P=0.267N P=0.669 P=0.222N P=0.469N | |POLY 1.5 | P=0.467 P=0.500N P=0.463 P=0.741 |P=0.269N P=0.668 P=0.225N P=0.473N | |POLY 6 | P=0.466 P=0.498N P=0.464 P=0.741 |P=0.263N P=0.665 P=0.218N P=0.463N | |LOGISTIC REGRESSION| P=0.512 (e) P=0.470 P=0.731N |P=0.222N P=0.672 (e) P=0.420N | |COCH-ARM / FISHERS | P=0.483 P=0.495N P=0.476 P=0.742 |P=0.270N P=0.666 P=0.232N P=0.476N | |ORDER RESTRICTED | P=0.343 (e) (e) (e) |P=0.222N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/50 (0%) 0/49 (0%) |3/48 (6%) 1/50 (2%) 1/50 (2%) 3/46 (7%) | |POLY-3 RATE (b) | 0/44.84 0/43.75 0/44.84 0/42.71 |3/40.81 1/43.63 1/44.22 3/42.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |7.4% 2.3% 2.3% 7.1% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |3/32 (9%) 1/33 (3%) 1/39 (3%) 3/38 (8%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.579 P=0.293N P=0.237N P=0.582N | |POLY 3 | (e) (e) (e) (e) |P=0.497 P=0.281N P=0.277N P=0.648N | |POLY 1.5 | (e) (e) (e) (e) |P=0.489 P=0.282N P=0.283N P=0.659N | |POLY 6 | (e) (e) (e) (e) |P=0.511 P=0.285N P=0.270N P=0.635N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.579 P=0.293N P=0.237N P=0.582N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.478 P=0.293N P=0.293N P=0.641 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.363N (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 | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/47 (4%) 3/50 (6%) 3/49 (6%) |0/48 (0%) 0/50 (0%) 1/50 (2%) 0/46 (0%) | |POLY-3 RATE (b) | 1/44.84 2/43.75 3/44.84 3/42.71 |0/40.81 0/43.63 1/44.22 0/42.13 | |POLY-3 PERCENT (g) | 2.2% 4.6% 6.7% 7.0% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 1/38 (3%) 2/40 (5%) 3/38 (8%) 3/36 (8%) |0/32 (0%) 0/33 (0%) 1/39 (3%) 0/38 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.199 P=0.518 P=0.305 P=0.286 |P=0.718 (e) P=0.539 (e) | |POLY 3 | P=0.209 P=0.491 P=0.305 P=0.288 |P=0.716 (e) P=0.516 (e) | |POLY 1.5 | P=0.214 P=0.488 P=0.306 P=0.292 |P=0.707 (e) P=0.512 (e) | |POLY 6 | P=0.203 P=0.497 P=0.305 P=0.285 |P=0.729 (e) P=0.520 (e) | |LOGISTIC REGRESSION| P=0.199 P=0.518 P=0.305 P=0.286 |(e) (e) P=0.539 (e) | |COCH-ARM / FISHERS | P=0.238 P=0.492 P=0.324 P=0.316 |P=0.690 (e) P=0.510 (e) | |ORDER RESTRICTED | P=0.248 (e) (e) (e) |P=0.394 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Cytoplasmic Alteration Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 5/50 (10%) 0/49 (0%) |2/48 (4%) 0/50 (0%) 4/50 (8%) 1/46 (2%) | |POLY-3 RATE (b) | 1/44.84 0/43.75 5/44.99 0/42.71 |2/41.24 0/43.63 4/44.22 1/42.13 | |POLY-3 PERCENT (g) | 2.2% 0.0% 11.1% 0.0% |4.9% 0.0% 9.0% 2.4% | |TERMINAL (d) | 1/38 (3%) 0/40 (0%) 4/38 (11%) 0/36 (0%) |1/32 (3%) 0/33 (0%) 4/39 (10%) 1/38 (3%) | |FIRST INCIDENCE | 729 (T) --- 690 --- |603 --- 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.586N P=0.490N P=0.103 P=0.511N |P=0.514N P=0.236N P=0.416 P=0.460N | |POLY 3 | P=0.588N P=0.505N P=0.102 P=0.510N |P=0.572N P=0.224N P=0.370 P=0.493N | |POLY 1.5 | P=0.579N P=0.507N P=0.102 P=0.508N |P=0.583N P=0.224N P=0.363 P=0.500N | |POLY 6 | P=0.597N P=0.502N P=0.102 P=0.511N |P=0.556N P=0.229N P=0.375 P=0.485N | |LOGISTIC REGRESSION| P=0.576N (e) P=0.102 (e) |P=0.574N P=0.230N P=0.369 P=0.512N | |COCH-ARM / FISHERS | P=0.544N P=0.505N P=0.112 P=0.495N |P=0.599N P=0.237N P=0.359 P=0.516N | |ORDER RESTRICTED | P=0.179 (e) (e) (e) |P=0.343 (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 | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/50 (0%) 0/49 (0%) |3/48 (6%) 2/50 (4%) 7/50 (14%) 3/46 (7%) | |POLY-3 RATE (b) | 1/44.84 0/43.75 0/44.84 0/42.71 |3/40.86 2/43.63 7/44.22 3/42.13 | |POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 0.0% |7.3% 4.6% 15.8% 7.1% | |TERMINAL (d) | 1/38 (3%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |2/32 (6%) 2/33 (6%) 7/39 (18%) 3/38 (8%) | |FIRST INCIDENCE | 729 (T) --- --- --- |715 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.313N P=0.490N P=0.500N P=0.511N |P=0.557 P=0.494N P=0.245 P=0.582N | |POLY 3 | P=0.297N P=0.505N P=0.500N P=0.510N |P=0.466 P=0.470N P=0.190 P=0.649N | |POLY 1.5 | P=0.297N P=0.507N P=0.500N P=0.508N |P=0.446 P=0.471N P=0.182 P=0.660N | |POLY 6 | P=0.297N P=0.502N P=0.500N P=0.511N |P=0.494 P=0.477N P=0.198 P=0.636N | |LOGISTIC REGRESSION| P=0.313N (e) (e) (e) |P=0.534 P=0.492N P=0.217 P=0.615N | |COCH-ARM / FISHERS | P=0.301N P=0.505N P=0.490N P=0.495N |P=0.414 P=0.480N P=0.176 P=0.641 | |ORDER RESTRICTED | P=0.130N (e) (e) (e) |P=0.292 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 2/43.48 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.6% | | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 2/36 (6%) | | |FIRST INCIDENCE | --- --- --- 729 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.221 | | |POLY 3 | P=0.043 * (e) (e) P=0.221 | | |POLY 1.5 | P=0.043 * (e) (e) P=0.224 | | |POLY 6 | P=0.042 * (e) (e) P=0.218 | | |LOGISTIC REGRESSION| (e) (e) (e) P=0.221 | | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 | | |ORDER RESTRICTED | P=0.024 * (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 | | | | | |=================================================================================================================================| | | |Preputial Gland | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 1/50 (2%) 4/50 (8%) | | |POLY-3 RATE (b) | 3/47.54 1/46.09 1/45.29 4/44.27 | | |POLY-3 PERCENT (g) | 6.3% 2.2% 2.2% 9.0% | | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 2/36 (6%) | | |FIRST INCIDENCE | 592 710 597 558 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.267 P=0.317N P=0.327N P=0.449 | | |POLY 3 | P=0.285 P=0.317N P=0.323N P=0.461 | | |POLY 1.5 | P=0.288 P=0.315N P=0.322N P=0.468 | | |POLY 6 | P=0.282 P=0.319N P=0.325N P=0.454 | | |LOGISTIC REGRESSION| P=0.329 P=0.277N P=0.248N P=0.543 | | |COCH-ARM / FISHERS | P=0.302 P=0.309N P=0.309N P=0.500 | | |ORDER RESTRICTED | P=0.177 (e) (e) (e) | | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 36 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 8/50 (16%) 10/50 (20%) 6/50 (12%) | | |POLY-3 RATE (b) | 11/47.24 8/46.16 10/44.90 6/43.71 | | |POLY-3 PERCENT (g) | 23.3% 17.3% 22.3% 13.7% | | |TERMINAL (d) | 7/39 (18%) 7/40 (18%) 9/38 (24%) 5/36 (14%) | | |FIRST INCIDENCE | 682 691 715 667 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.213N P=0.302N P=0.535N P=0.204N | | |POLY 3 | P=0.195N P=0.324N P=0.553N P=0.184N | | |POLY 1.5 | P=0.186N P=0.324N P=0.547N P=0.176N | | |POLY 6 | P=0.206N P=0.325N P=0.561N P=0.194N | | |LOGISTIC REGRESSION| P=0.202N P=0.317N P=0.546N P=0.187N | | |COCH-ARM / FISHERS | P=0.150N P=0.306N P=0.500N P=0.143N | | |ORDER RESTRICTED | P=0.194N (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 | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | | |POLY-3 RATE (b) | 0/46.83 1/46.24 0/44.84 2/44.70 | | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 4.5% | | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) | | |FIRST INCIDENCE | --- 670 --- 484 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.128 P=0.496 (e) P=0.224 | | |POLY 3 | P=0.132 P=0.497 (e) P=0.227 | | |POLY 1.5 | P=0.133 P=0.497 (e) P=0.228 | | |POLY 6 | P=0.132 P=0.499 (e) P=0.227 | | |LOGISTIC REGRESSION| P=0.178 P=0.516 (e) P=0.341 | | |COCH-ARM / FISHERS | P=0.140 P=0.500 (e) P=0.247 | | |ORDER RESTRICTED | P=0.068 (e) (e) (e) | | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 37 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | | |POLY-3 RATE (b) | 2/46.83 1/46.01 0/44.84 0/43.48 | | |POLY-3 PERCENT (g) | 4.3% 2.2% 0.0% 0.0% | | |TERMINAL (d) | 2/39 (5%) 1/40 (3%) 0/38 (0%) 0/36 (0%) | | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.109N P=0.491N P=0.244N P=0.256N | | |POLY 3 | P=0.103N P=0.506N P=0.247N P=0.254N | | |POLY 1.5 | P=0.103N P=0.507N P=0.247N P=0.251N | | |POLY 6 | P=0.104N P=0.505N P=0.247N P=0.257N | | |LOGISTIC REGRESSION| P=0.109N P=0.491N (e) (e) | | |COCH-ARM / FISHERS | P=0.101N P=0.500N P=0.247N P=0.247N | | |ORDER RESTRICTED | P=0.086N (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: Site of Application | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 1/46.45 1/45.12 0/43.48 |2/43.17 1/43.63 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.2% 0.0% |4.6% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 603 653 --- |603 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.611N P=0.504 P=0.496 (e) |P=0.089N P=0.507N P=0.228N P=0.220N | |POLY 3 | P=0.615N P=0.498 P=0.493 (e) |P=0.099N P=0.496N P=0.232N P=0.227N | |POLY 1.5 | P=0.611N P=0.497 P=0.492 (e) |P=0.100N P=0.495N P=0.235N P=0.230N | |POLY 6 | P=0.618N P=0.500 P=0.493 (e) |P=0.097N P=0.504N P=0.229N P=0.225N | |LOGISTIC REGRESSION| P=0.562N P=0.558 P=0.525 (e) |P=0.100N P=0.499N P=0.238N P=0.244N | |COCH-ARM / FISHERS | P=0.595N P=0.500 P=0.500 (e) |P=0.101N P=0.500N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.400 (e) (e) (e) |P=0.068N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 38 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Site of Application - Dermis | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 9/50 (18%) 1/50 (2%) |3/50 (6%) 2/50 (4%) 7/50 (14%) 2/50 (4%) | |POLY-3 RATE (b) | 2/46.83 2/46.67 9/45.12 1/43.48 |3/43.78 2/43.63 7/44.22 2/45.13 | |POLY-3 PERCENT (g) | 4.3% 4.3% 20.0% 2.3% |6.9% 4.6% 15.8% 4.4% | |TERMINAL (d) | 2/39 (5%) 0/40 (0%) 8/38 (21%) 1/36 (3%) |1/33 (3%) 2/33 (6%) 7/39 (18%) 2/40 (5%) | |FIRST INCIDENCE | 729 (T) 603 653 729 (T) |506 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.559 P=0.688N P=0.025 * P=0.528N |P=0.430N P=0.494N P=0.221 P=0.442N | |POLY 3 | P=0.540 P=0.692 P=0.021 * P=0.526N |P=0.513N P=0.502N P=0.161 P=0.486N | |POLY 1.5 | P=0.556 P=0.690 P=0.021 * P=0.521N |P=0.521N P=0.497N P=0.158 P=0.489N | |POLY 6 | P=0.522 P=0.690N P=0.021 * P=0.531N |P=0.500N P=0.513N P=0.162 P=0.483N | |LOGISTIC REGRESSION| P=0.568N P=0.680N P=0.022 * P=0.528N |P=0.518N P=0.506N P=0.162 P=0.515N | |COCH-ARM / FISHERS | P=0.537N P=0.691N P=0.026 * P=0.500N |P=0.537N P=0.500N P=0.159 P=0.500N | |ORDER RESTRICTED | P=0.153N (e) (e) (e) |P=0.324N (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: Site of Application - Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 10/50 (20%) 1/50 (2%) |5/50 (10%) 3/50 (6%) 7/50 (14%) 7/50 (14%) | |POLY-3 RATE (b) | 2/46.83 3/46.45 10/45.12 1/43.48 |5/44.12 3/44.15 7/44.22 7/46.32 | |POLY-3 PERCENT (g) | 4.3% 6.5% 22.2% 2.3% |11.3% 6.8% 15.8% 15.1% | |TERMINAL (d) | 2/39 (5%) 2/40 (5%) 9/38 (24%) 1/36 (3%) |1/33 (3%) 2/33 (6%) 7/39 (18%) 5/40 (13%) | |FIRST INCIDENCE | 729 (T) 603 653 729 (T) |506 568 729 (T) 528 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.556N P=0.511 P=0.014 * P=0.528N |P=0.302 P=0.356N P=0.469 P=0.474 | |POLY 3 | P=0.565 P=0.496 P=0.011 * P=0.526N |P=0.228 P=0.356N P=0.380 P=0.414 | |POLY 1.5 | P=0.559N P=0.494 P=0.011 * P=0.521N |P=0.218 P=0.351N P=0.378 P=0.404 | |POLY 6 | P=0.547 P=0.500 P=0.011 * P=0.531N |P=0.243 P=0.369N P=0.380 P=0.422 | |LOGISTIC REGRESSION| P=0.544N P=0.500 P=0.012 * P=0.528N |P=0.202 P=0.366N P=0.385 P=0.357 | |COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.014 * P=0.500N |P=0.200 P=0.357N P=0.380 P=0.380 | |ORDER RESTRICTED | P=0.108N (e) (e) (e) |P=0.280 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 39 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Subcutaneous Tissue | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.83 0/46.01 0/44.84 2/44.11 |1/43.38 2/44.01 0/44.22 1/45.56 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.5% |2.3% 4.5% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- 558 |488 619 --- 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.042 * (e) (e) P=0.224 |P=0.478N P=0.508 P=0.500N P=0.750N | |POLY 3 | P=0.043 * (e) (e) P=0.224 |P=0.491N P=0.505 P=0.496N P=0.750N | |POLY 1.5 | P=0.043 * (e) (e) P=0.226 |P=0.494N P=0.505 P=0.499N P=0.753N | |POLY 6 | P=0.043 * (e) (e) P=0.223 |P=0.487N P=0.501 P=0.494N P=0.745N | |LOGISTIC REGRESSION| P=0.051 (e) (e) P=0.267 |P=0.519N P=0.485 P=0.486N P=0.731 | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |P=0.500N P=0.500 P=0.500N P=0.753N | |ORDER RESTRICTED | P=0.025 * (e) (e) (e) |P=0.367N (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 | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 15/49 (31%) 13/50 (26%) 14/50 (28%) 13/47 (28%) |24/49 (49%) 21/49 (43%) 18/50 (36%) 13/50 (26%) | |POLY-3 RATE (b) | 15/48.35 13/46.82 14/46.50 13/42.78 |24/45.14 21/47.08 18/46.88 13/45.83 | |POLY-3 PERCENT (g) | 31.0% 27.8% 30.1% 30.4% |53.2% 44.6% 38.4% 28.4% | |TERMINAL (d) | 9/39 (23%) 10/40 (25%) 9/38 (24%) 7/35 (20%) |15/33 (46%) 10/33 (30%) 13/39 (33%) 10/40 (25%) | |FIRST INCIDENCE | 515 603 496 474 |305 12 67 604 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.533 P=0.406N P=0.541N P=0.538N |P=0.005N** P=0.366N P=0.086N P=0.008N** | |POLY 3 | P=0.533 P=0.451N P=0.550N P=0.564N |P=0.009N** P=0.269N P=0.110N P=0.012N* | |POLY 1.5 | P=0.538N P=0.436N P=0.540N P=0.546N |P=0.009N** P=0.280N P=0.116N P=0.012N* | |POLY 6 | P=0.522 P=0.465N P=0.559N P=0.577N |P=0.009N** P=0.267N P=0.109N P=0.012N* | |LOGISTIC REGRESSION| P=0.470N P=0.369N P=0.446N P=0.428N |P=0.010N* P=0.356N P=0.135N P=0.013N* | |COCH-ARM / FISHERS | P=0.463N P=0.387N P=0.474N P=0.463N |P=0.009N** P=0.343N P=0.135N P=0.015N* | |ORDER RESTRICTED | P=0.666N (e) (e) (e) |P=0.010N* (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 40 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 5/50 (10%) 1/50 (2%) 1/47 (2%) |6/49 (12%) 12/49 (24%) 12/50 (24%) 6/50 (12%) | |POLY-3 RATE (b) | 2/46.28 5/46.01 1/44.99 1/40.78 |6/42.08 12/42.91 12/44.22 6/45.13 | |POLY-3 PERCENT (g) | 4.3% 10.9% 2.2% 2.5% |14.3% 28.0% 27.1% 13.3% | |TERMINAL (d) | 2/39 (5%) 5/40 (13%) 0/38 (0%) 1/35 (3%) |5/33 (15%) 12/33 (36%) 12/39 (31%) 6/40 (15%) | |FIRST INCIDENCE | 729 (T) 729 (T) 690 729 (T) |698 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.230N P=0.226 P=0.512N P=0.538N |P=0.213N P=0.088 P=0.172 P=0.485N | |POLY 3 | P=0.234N P=0.214 P=0.510N P=0.544N |P=0.321N P=0.098 P=0.112 P=0.571N | |POLY 1.5 | P=0.229N P=0.215 P=0.509N P=0.538N |P=0.339N P=0.100 P=0.107 P=0.581N | |POLY 6 | P=0.239N P=0.213 P=0.511N P=0.549N |P=0.301N P=0.089 P=0.117 P=0.562N | |LOGISTIC REGRESSION| P=0.239N P=0.226 P=0.509N P=0.538N |P=0.243N P=0.077 P=0.134 P=0.538N | |COCH-ARM / FISHERS | P=0.206N P=0.226 P=0.492N P=0.516N |P=0.380N P=0.096 P=0.104 P=0.606N | |ORDER RESTRICTED | P=0.211N (e) (e) (e) |P=0.193N (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 | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/49 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 1/46.01 0/44.84 0/43.48 |2/43.35 0/42.91 2/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |4.6% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/39 (0%) 1/40 (3%) 0/38 (0%) 0/36 (0%) |1/33 (3%) 0/33 (0%) 2/39 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- |506 --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.582N P=0.505 (e) (e) |P=0.212N P=0.233N P=0.646N P=0.214N | |POLY 3 | P=0.575N P=0.496 (e) (e) |P=0.237N P=0.239N P=0.687N P=0.228N | |POLY 1.5 | P=0.574N P=0.496 (e) (e) |P=0.241N P=0.239N P=0.691N P=0.231N | |POLY 6 | P=0.575N P=0.497 (e) (e) |P=0.231N P=0.243N P=0.682N P=0.225N | |LOGISTIC REGRESSION| (e) P=0.505 (e) (e) |P=0.248N P=0.250N P=0.695 P=0.254N | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.246N P=0.253N P=0.691N P=0.247N | |ORDER RESTRICTED | P=0.391N (e) (e) (e) |P=0.109N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 41 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/49 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.83 1/46.27 0/44.84 0/43.48 |1/43.61 1/43.44 0/44.22 2/46.08 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |2.3% 2.3% 0.0% 4.3% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 660 --- --- |305 568 --- 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.579N P=0.500 (e) (e) |P=0.373 P=0.753N P=0.504N P=0.510 | |POLY 3 | P=0.574N P=0.498 (e) (e) |P=0.381 P=0.760 P=0.497N P=0.519 | |POLY 1.5 | P=0.574N P=0.497 (e) (e) |P=0.376 P=0.759 P=0.500N P=0.512 | |POLY 6 | P=0.574N P=0.499 (e) (e) |P=0.389 P=0.759 P=0.494N P=0.529 | |LOGISTIC REGRESSION| P=0.556N P=0.522 (e) (e) |P=0.325 P=0.748 P=0.451N P=0.419 | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.369 P=0.747 P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.392N (e) (e) (e) |P=0.293 (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 | | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 3/50 (6%) 2/50 (4%) |4/50 (8%) 4/49 (8%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.83 2/46.27 3/45.07 2/43.71 |4/43.35 4/43.72 2/44.22 1/45.70 | |POLY-3 PERCENT (g) | 4.3% 4.3% 6.7% 4.6% |9.2% 9.2% 4.5% 2.2% | |TERMINAL (d) | 2/39 (5%) 1/40 (3%) 2/38 (5%) 1/36 (3%) |3/33 (9%) 2/33 (6%) 2/39 (5%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 660 669 667 |506 568 729 (T) 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.527 P=0.686N P=0.486 P=0.663 |P=0.071N P=0.634N P=0.275N P=0.145N | |POLY 3 | P=0.530 P=0.689 P=0.483 P=0.669 |P=0.085N P=0.639N P=0.328N P=0.163N | |POLY 1.5 | P=0.537 P=0.688 P=0.482 P=0.673 |P=0.088N P=0.641N P=0.334N P=0.168N | |POLY 6 | P=0.524 P=0.692 P=0.484 P=0.666 |P=0.080N P=0.641N P=0.321N P=0.157N | |LOGISTIC REGRESSION| P=0.548 P=0.691 P=0.481 P=0.672 |P=0.096N P=0.630 P=0.333N P=0.192N | |COCH-ARM / FISHERS | P=0.569 P=0.691N P=0.500 P=0.691N |P=0.094N P=0.631 P=0.339N P=0.181N | |ORDER RESTRICTED | P=0.598 (e) (e) (e) |P=0.130N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 42 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/47 (2%) 1/48 (2%) 0/47 (0%) |0/49 (0%) 0/48 (0%) 0/47 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 4/48.14 1/44.22 1/43.09 0/40.99 |0/41.96 0/42.09 0/43.26 1/46.12 | |POLY-3 PERCENT (g) | 8.3% 2.3% 2.3% 0.0% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 1/38 (3%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 515 545 729 (T) --- |--- --- --- 105 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.042N* P=0.189N P=0.200N P=0.081N |P=0.202 (e) (e) P=0.504 | |POLY 3 | P=0.042N* P=0.206N P=0.214N P=0.083N |P=0.213 (e) (e) P=0.519 | |POLY 1.5 | P=0.040N* P=0.206N P=0.211N P=0.080N |P=0.211 (e) (e) P=0.515 | |POLY 6 | P=0.043N* P=0.205N P=0.218N P=0.087N |P=0.217 (e) (e) P=0.522 | |LOGISTIC REGRESSION| P=0.025N* P=0.118N P=0.144N P=0.038N* |P=0.099 (e) (e) P=0.369 | |COCH-ARM / FISHERS | P=0.038N* P=0.201N P=0.194N P=0.066N |P=0.203 (e) (e) P=0.505 | |ORDER RESTRICTED | P=0.020N* (e) (e) (e) |P=0.138 (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 | | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/47 (4%) 1/44 (2%) 2/47 (4%) 0/46 (0%) |0/46 (0%) 0/48 (0%) 0/44 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/44.38 1/40.97 2/42.02 0/40.71 |0/38.72 0/42.72 0/38.87 0/42.13 | |POLY-3 PERCENT (g) | 4.5% 2.4% 4.8% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/38 (5%) 0/36 (0%) 2/36 (6%) 0/34 (0%) |0/30 (0%) 0/33 (0%) 0/35 (0%) 0/37 (0%) | |FIRST INCIDENCE | 729 (T) 670 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.225N P=0.515N P=0.676 P=0.263N |(e) (e) (e) (e) | |POLY 3 | P=0.217N P=0.528N P=0.674 P=0.257N |(e) (e) (e) (e) | |POLY 1.5 | P=0.213N P=0.529N P=0.676 P=0.253N |(e) (e) (e) (e) | |POLY 6 | P=0.223N P=0.526N P=0.672 P=0.261N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.214N P=0.526N P=0.676 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.200N P=0.525N P=0.692N P=0.253N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.171N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 43 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/47 (2%) 0/44 (0%) 0/47 (0%) 0/46 (0%) |5/46 (11%) 4/48 (8%) 4/44 (9%) 1/47 (2%) | |POLY-3 RATE (b) | 1/44.38 0/40.74 0/42.02 0/40.71 |5/38.72 4/42.72 4/39.31 1/42.13 | |POLY-3 PERCENT (g) | 2.3% 0.0% 0.0% 0.0% |12.9% 9.4% 10.2% 2.4% | |TERMINAL (d) | 1/38 (3%) 0/36 (0%) 0/36 (0%) 0/34 (0%) |5/30 (17%) 4/33 (12%) 3/35 (9%) 1/37 (3%) | |FIRST INCIDENCE | 729 (T) --- --- --- |729 (T) 729 (T) 603 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.318N P=0.511N P=0.511N P=0.522N |P=0.047N* P=0.439N P=0.414N P=0.061N | |POLY 3 | P=0.302N P=0.517N P=0.511N P=0.517N |P=0.069N P=0.438N P=0.490N P=0.082N | |POLY 1.5 | P=0.303N P=0.517N P=0.510N P=0.514N |P=0.073N P=0.447N P=0.510N P=0.086N | |POLY 6 | P=0.300N P=0.517N P=0.512N P=0.521N |P=0.063N P=0.436N P=0.467N P=0.077N | |LOGISTIC REGRESSION| P=0.318N (e) (e) (e) |P=0.063N P=0.439N P=0.492N P=0.061N | |COCH-ARM / FISHERS | P=0.306N P=0.516N P=0.500N P=0.505N |P=0.080N P=0.473N P=0.529N P=0.097N | |ORDER RESTRICTED | P=0.136N (e) (e) (e) |P=0.068N (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 | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.28 0/46.01 0/44.84 0/43.48 |0/42.68 2/43.63 3/44.22 1/45.13 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.6% 6.8% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 2/33 (6%) 3/39 (8%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.524 P=0.238 P=0.152 P=0.538 | |POLY 3 | (e) (e) (e) (e) |P=0.479 P=0.242 P=0.125 P=0.511 | |POLY 1.5 | (e) (e) (e) (e) |P=0.468 P=0.242 P=0.122 P=0.508 | |POLY 6 | (e) (e) (e) (e) |P=0.493 P=0.239 P=0.128 P=0.515 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.238 P=0.152 P=0.538 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.444 P=0.247 P=0.121 P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.191 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 44 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 3/50 (6%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.28 3/46.01 0/44.84 0/43.48 |0/42.68 2/44.10 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 2.2% 6.5% 0.0% 0.0% |0.0% 4.5% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 3/40 (8%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 1/33 (3%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |--- 588 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.167N P=0.314 P=0.505N P=0.516N |P=0.383N P=0.242 (e) (e) | |POLY 3 | P=0.163N P=0.303 P=0.506N P=0.512N |P=0.389N P=0.244 (e) (e) | |POLY 1.5 | P=0.161N P=0.304 P=0.505N P=0.509N |P=0.394N P=0.243 (e) (e) | |POLY 6 | P=0.166N P=0.302 P=0.507N P=0.516N |P=0.386N P=0.243 (e) (e) | |LOGISTIC REGRESSION| P=0.167N P=0.314 (e) (e) |P=0.410N P=0.234 (e) (e) | |COCH-ARM / FISHERS | P=0.150N P=0.316 P=0.495N P=0.495N |P=0.405N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.125N (e) (e) (e) |P=0.243N (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: Follicle | | Degeneration Cystic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 6/50 (12%) 8/50 (16%) 6/50 (12%) |14/50 (28%) 14/50 (28%) 18/50 (36%) 12/50 (24%) | |POLY-3 RATE (b) | 4/46.49 6/46.24 8/45.46 6/44.22 |14/45.53 14/45.20 18/45.16 12/45.70 | |POLY-3 PERCENT (g) | 8.6% 13.0% 17.6% 13.6% |30.8% 31.0% 39.9% 26.3% | |TERMINAL (d) | 3/39 (8%) 4/40 (10%) 5/38 (13%) 4/36 (11%) |7/33 (21%) 8/33 (24%) 15/39 (39%) 11/40 (28%) | |FIRST INCIDENCE | 672 691 653 558 |365 568 579 551 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.268 P=0.381 P=0.170 P=0.320 |P=0.215N P=0.577N P=0.424 P=0.263N | |POLY 3 | P=0.284 P=0.366 P=0.166 P=0.338 |P=0.386N P=0.581 P=0.245 P=0.404N | |POLY 1.5 | P=0.294 P=0.368 P=0.167 P=0.346 |P=0.386N P=0.588N P=0.245 P=0.401N | |POLY 6 | P=0.275 P=0.365 P=0.166 P=0.331 |P=0.385N P=0.558 P=0.245 P=0.411N | |LOGISTIC REGRESSION| P=0.305 P=0.367 P=0.170 P=0.363 |P=0.369N P=0.587N P=0.267 P=0.404N | |COCH-ARM / FISHERS | P=0.341 P=0.383 P=0.188 P=0.383 |P=0.396N P=0.588N P=0.260 P=0.410N | |ORDER RESTRICTED | P=0.259 (e) (e) (e) |P=0.345N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 45 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/49 (14%) 7/50 (14%) 8/50 (16%) 3/50 (6%) |1/50 (2%) 11/50 (22%) 9/50 (18%) 4/50 (8%) | |POLY-3 RATE (b) | 7/46.28 7/46.01 8/44.90 3/43.80 |1/42.68 11/43.96 9/44.51 4/45.17 | |POLY-3 PERCENT (g) | 15.1% 15.2% 17.8% 6.9% |2.3% 25.0% 20.2% 8.9% | |TERMINAL (d) | 7/39 (18%) 7/40 (18%) 7/38 (18%) 2/36 (6%) |1/33 (3%) 9/33 (27%) 8/39 (21%) 3/40 (8%) | |FIRST INCIDENCE | 729 (T) 729 (T) 713 642 |729 (T) 683 653 718 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.170N P=0.595N P=0.478 P=0.192N |P=0.472N P=0.003 ** P=0.018 * P=0.243 | |POLY 3 | P=0.159N P=0.609 P=0.475 P=0.181N |P=0.554 P=0.002 ** P=0.009 ** P=0.196 | |POLY 1.5 | P=0.153N P=0.610 P=0.479 P=0.175N |P=0.531 P=0.002 ** P=0.009 ** P=0.191 | |POLY 6 | P=0.166N P=0.608 P=0.471 P=0.186N |P=0.543N P=0.002 ** P=0.010 * P=0.203 | |LOGISTIC REGRESSION| P=0.171N P=0.595N P=0.458 P=0.189N |P=0.554N P=0.002 ** P=0.012 * P=0.215 | |COCH-ARM / FISHERS | P=0.124N P=0.597N P=0.517 P=0.151N |P=0.486 P=0.002 ** P=0.008 ** P=0.181 | |ORDER RESTRICTED | P=0.160N (e) (e) (e) |P=0.021 * (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 | | | | | |=================================================================================================================================| | | |Tooth | | Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 18/18 (100%) 11/11 (100%) 15/15 (100%) 12/12 (100%)|0/1 (0%) 1/1 (100%) 0/1 (0%) 1/2 (50%) | |POLY-3 RATE (b) | 18/18.00 11/11.00 15/15.00 12/12.00 |0/0.30 1/1.00 0/1.00 1/1.57 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% |0.0% 100.0% 0.0% 63.7% | |TERMINAL (d) | 16/16 (100%) 10/10 (100%) 13/13 (100%) 10/10 (100%)|0/0 (0%) 0/0 (0%) 0/1 (0%) 1/1 (100%) | |FIRST INCIDENCE | 640 710 690 573 |--- 653 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.685 P=0.506 (e) P=1.000N | |POLY 3 | (e) (e) (e) (e) |P=0.703N P=1.000N (e) P=0.764 | |POLY 1.5 | (e) (e) (e) (e) |P=0.690 P=1.000N (e) P=0.691 | |POLY 6 | (e) (e) (e) (e) |P=0.752N P=1.000N (e) P=0.896 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.710N (e) (e) P=1.000N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.590 P=0.500 (e) P=0.667 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.566 (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 46 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | | | | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/49 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.83 1/46.24 0/44.29 2/44.70 |0/42.68 0/43.63 0/44.22 0/45.13 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 4.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/36 (0%) |0/33 (0%) 0/33 (0%) 0/39 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 670 --- 484 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.128 P=0.496 (e) P=0.224 |(e) (e) (e) (e) | |POLY 3 | P=0.133 P=0.497 (e) P=0.227 |(e) (e) (e) (e) | |POLY 1.5 | P=0.133 P=0.497 (e) P=0.228 |(e) (e) (e) (e) | |POLY 6 | P=0.133 P=0.499 (e) P=0.227 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.179 P=0.516 (e) P=0.341 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.140 P=0.500 (e) P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.068 (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 | | | | | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 8/50 (16%) 6/50 (12%) 2/50 (4%) | |POLY-3 RATE (b) | |5/43.07 8/45.24 6/44.39 2/45.84 | |POLY-3 PERCENT (g) | |11.6% 17.7% 13.5% 4.4% | |TERMINAL (d) | |4/33 (12%) 3/33 (9%) 5/39 (13%) 1/40 (3%) | |FIRST INCIDENCE | |619 568 687 481 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.075N P=0.289 P=0.600 P=0.166N | |POLY 3 | |P=0.090N P=0.307 P=0.521 P=0.191N | |POLY 1.5 | |P=0.097N P=0.299 P=0.510 P=0.199N | |POLY 6 | |P=0.083N P=0.311 P=0.533 P=0.184N | |LOGISTIC REGRESSION| |P=0.110N P=0.279 P=0.529 P=0.218N | |COCH-ARM / FISHERS | |P=0.113N P=0.277 P=0.500 P=0.218N | |ORDER RESTRICTED | |P=0.098N (e) (e) (e) | |=================================================================================================================================| Date: 07/19/04 EXPERIMENT: 93020 TEST: 08 Page 47 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |46/50 (92%) 44/50 (88%) 47/50 (94%) 49/50 (98%) | |POLY-3 RATE (b) | |46/48.88 44/47.67 47/47.19 49/49.00 | |POLY-3 PERCENT (g) | |94.1% 92.3% 99.6% 100.0% | |TERMINAL (d) | |31/33 (94%) 32/33 (97%) 39/39 (100%) 40/40 (100%) | |FIRST INCIDENCE | |305 555 560 481 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.192N P=0.421N P=0.196N P=0.243N | |POLY 3 | |P=0.026 * P=0.522N P=0.160 P=0.125 | |POLY 1.5 | |P=0.029 * P=0.445N P=0.202 P=0.127 | |POLY 6 | |P=0.027 * P=0.643N P=0.144 P=0.130 | |LOGISTIC REGRESSION| |P=0.090 P=0.282N P=0.485 P=0.238 | |COCH-ARM / FISHERS | |P=0.080 P=0.370N P=0.500 P=0.181 | |ORDER RESTRICTED | |P=0.030 * (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).