TDMS Study 56111-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANS-CINNAMALDEHYDE DATE: 06/14/01 EXPERIMENT: 56111 TEST: 04 TIME: 09:30:33 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: 56111B PATHOLOGIST: MARIT, GARY CAS: 14371-10-9 ------------------------------------------------------------------------------------------------------------------------------------ Final#1/Mice REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 003 VEHICLE CONTROL INCLUDE 004 VEHICLE CONTROL INCLUDE 005 .312% INCLUDE 006 .312% INCLUDE 007 .625% INCLUDE 008 .625% INCLUDE 009 1.25% INCLUDE 010 1.25% NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANS-CINNAMALDEHYDE DATE: 06/14/01 EXPERIMENT: 56111 TEST: 04 TIME: 09:30:33 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: 56111B PATHOLOGIST: MARIT, GARY CAS: 14371-10-9 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANS-CINNAMALDEHYDE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Heart Mineralization Kidney Infarct Infiltration Cellular Lymphocyte Mineralization Nephropathy Liver Inflammation Liver: Portal Infiltration Cellular Lymphocyte Nose: Olfactory Epithelium Pigmentation Preputial Gland Inflammation Preputial Gland: Duct Ectasia =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Bone Myelofibrosis Kidney Infiltration Cellular Lymphocyte Nephropathy Liver Clear Cell Focus Mesentery: Fat Mineralization Nose: Olfactory Epithelium Degeneration Hyaline Pigmentation Stomach, Forestomach Ulcer Thyroid Gland: Follicle Cyst Urinary Bladder Inflammation Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) |2/50 (4%) 6/50 (12%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 1/44.02 0/49.55 |2/46.06 6/45.42 2/47.80 2/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.3% 13.2% 4.2% 4.3% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 1/39 (3%) 0/49 (0%) |2/41 (5%) 6/37 (16%) 2/44 (5%) 2/43 (5%) | |FIRST INCIDENCE | --- --- 728 (T) --- |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.693 (e) P=0.463 (e) |P=0.301N P=0.103 P=0.669N P=0.678N | |POLY 3 | P=0.708 (e) P=0.481 (e) |P=0.334N P=0.128 P=0.680N P=0.690N | |POLY 1.5 | P=0.705 (e) P=0.488 (e) |P=0.340N P=0.131 P=0.685N P=0.693N | |POLY 6 | P=0.711 (e) P=0.473 (e) |P=0.328N P=0.123 P=0.676N P=0.686N | |LOGISTIC REGRESSION| (e) (e) P=0.463 (e) |P=0.301N P=0.103 P=0.669N P=0.678N | |COCH-ARM / FISHERS | P=0.694 (e) P=0.495 (e) |P=0.343N P=0.134 P=0.691N P=0.691N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 22/50 (44%) 24/49 (49%) 19/50 (38%) |4/50 (8%) 2/50 (4%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 23/48.41 22/48.44 24/44.12 19/49.55 |4/46.06 2/45.42 2/47.80 1/46.54 | |POLY-3 PERCENT (g) | 47.5% 45.4% 54.4% 38.4% |8.7% 4.4% 4.2% 2.2% | |TERMINAL (d) | 23/47 (49%) 21/46 (46%) 23/39 (59%) 19/49 (39%) |4/41 (10%) 2/37 (5%) 2/44 (5%) 1/43 (2%) | |FIRST INCIDENCE | 728 (T) 644 702 728 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.207N P=0.538N P=0.178 P=0.214N |P=0.117N P=0.385N P=0.305N P=0.166N | |POLY 3 | P=0.222N P=0.499N P=0.325 P=0.239N |P=0.132N P=0.344N P=0.320N P=0.176N | |POLY 1.5 | P=0.223N P=0.500N P=0.389 P=0.242N |P=0.135N P=0.341N P=0.327N P=0.179N | |POLY 6 | P=0.221N P=0.500N P=0.258 P=0.236N |P=0.128N P=0.351N P=0.314N P=0.172N | |LOGISTIC REGRESSION| P=0.226N P=0.516N P=0.182 P=0.214N |P=0.117N P=0.385N P=0.305N P=0.166N | |COCH-ARM / FISHERS | P=0.254N P=0.500N P=0.462 P=0.272N |P=0.137N P=0.339N P=0.339N P=0.181N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |34/50 (68%) 26/50 (52%) 32/50 (64%) 29/50 (58%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/44.02 0/49.55 |34/46.48 26/45.66 32/48.34 29/47.03 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |73.2% 56.9% 66.2% 61.7% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |33/41 (81%) 25/37 (68%) 31/44 (71%) 28/43 (65%) | |FIRST INCIDENCE | --- --- --- --- |609 668 568 587 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.124N P=0.167N P=0.218N P=0.104N | |POLY 3 | (e) (e) (e) (e) |P=0.254N P=0.071N P=0.301N P=0.162N | |POLY 1.5 | (e) (e) (e) (e) |P=0.292N P=0.070N P=0.344N P=0.185N | |POLY 6 | (e) (e) (e) (e) |P=0.208N P=0.080N P=0.263N P=0.138N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.215N P=0.098N P=0.272N P=0.147N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.321N P=0.076N P=0.417N P=0.204N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |34/50 (68%) 31/50 (62%) 37/50 (74%) 33/50 (66%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/44.02 0/49.55 |34/46.19 31/46.33 37/47.80 33/47.51 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |73.6% 66.9% 77.4% 69.5% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |33/41 (81%) 30/37 (81%) 37/44 (84%) 32/43 (74%) | |FIRST INCIDENCE | --- --- --- --- |698 325 733 (T) 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.274N P=0.577 P=0.553 P=0.352N | |POLY 3 | (e) (e) (e) (e) |P=0.473N P=0.310N P=0.423 P=0.412N | |POLY 1.5 | (e) (e) (e) (e) |P=0.518N P=0.310N P=0.385 P=0.448N | |POLY 6 | (e) (e) (e) (e) |P=0.413N P=0.344N P=0.458 P=0.379N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.486N P=0.386N P=0.518 P=0.462N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.510 P=0.338N P=0.330 P=0.500N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 46/50 (92%) 43/50 (86%) 44/49 (90%) 42/50 (84%) |49/50 (98%) 50/50 (100%) 50/50 (100%) 49/50 (98%) | |POLY-3 RATE (b) | 46/50.00 43/48.89 44/48.47 42/50.00 |49/49.24 50/50.00 50/50.00 49/49.97 | |POLY-3 PERCENT (g) | 92.0% 88.0% 90.8% 84.0% |99.5% 100.0% 100.0% 98.1% | |TERMINAL (d) | 43/47 (92%) 41/46 (89%) 35/39 (90%) 41/49 (84%) |41/41 (100%) 37/37 (100%) 44/44 (100%) 43/43 (100%) | |FIRST INCIDENCE | 100 594 365 596 |463 325 425 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.146N P=0.384N P=0.141 P=0.105N |P=0.165N P=0.176 P=0.365N P=0.387N | |POLY 3 | P=0.156N P=0.369N P=0.557N P=0.179N |P=0.304N P=0.999 P=0.999 P=0.609N | |POLY 1.5 | P=0.158N P=0.361N P=0.528N P=0.179N |P=0.413N P=0.848 P=0.848 P=0.679N | |POLY 6 | P=0.154N P=0.379N P=0.591N P=0.179N |P=0.234N P=1.000 P=1.000 P=0.552N | |LOGISTIC REGRESSION| P=0.162N P=0.265N P=0.474N (e) |P=0.655N P=0.396 P=0.597 P=0.726 | |COCH-ARM / FISHERS | P=0.188N P=0.262N P=0.487N P=0.178N |P=0.595N P=0.500 P=0.500 P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%) |1/50 (2%) 3/50 (6%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.41 1/48.13 0/44.02 0/49.55 |1/46.06 3/45.42 2/47.80 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 2.1% 0.0% 0.0% |2.2% 6.6% 4.2% 0.0% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 0/39 (0%) 0/49 (0%) |1/41 (2%) 3/37 (8%) 2/44 (5%) 0/43 (0%) | |FIRST INCIDENCE | --- 728 (T) --- --- |733 (T) 733 (T) 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.560N P=0.496 (e) (e) |P=0.218N P=0.269 P=0.525 P=0.490N | |POLY 3 | P=0.571N P=0.499 (e) (e) |P=0.236N P=0.300 P=0.513 P=0.498N | |POLY 1.5 | P=0.569N P=0.499 (e) (e) |P=0.240N P=0.303 P=0.508 P=0.500N | |POLY 6 | P=0.573N P=0.498 (e) (e) |P=0.232N P=0.295 P=0.518 P=0.496N | |LOGISTIC REGRESSION| (e) P=0.496 (e) (e) |P=0.218N P=0.269 P=0.525 (e) | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.242N P=0.309 P=0.500 P=0.500N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone | | Myelofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |27/50 (54%) 23/50 (46%) 34/50 (68%) 38/50 (76%) | |POLY-3 RATE (b) | 1/48.41 1/48.13 0/44.90 1/49.55 |27/46.62 23/46.23 34/48.36 38/46.54 | |POLY-3 PERCENT (g) | 2.1% 2.1% 0.0% 2.0% |57.9% 49.8% 70.3% 81.7% | |TERMINAL (d) | 1/47 (2%) 1/46 (2%) 0/39 (0%) 1/49 (2%) |25/41 (61%) 21/37 (57%) 32/44 (73%) 38/43 (88%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- 728 (T) |609 575 568 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.605N P=0.757 P=0.537N P=0.752N |P=0.009 ** P=0.450N P=0.209 P=0.023 * | |POLY 3 | P=0.618N P=0.759 P=0.515N P=0.755N |P<0.001 ** P=0.278N P=0.144 P=0.008 ** | |POLY 1.5 | P=0.616N P=0.760 P=0.508N P=0.756N |P<0.001 ** P=0.274N P=0.129 P=0.010 * | |POLY 6 | P=0.620N P=0.758 P=0.523N P=0.755N |P<0.001 ** P=0.297N P=0.157 P=0.008 ** | |LOGISTIC REGRESSION| P=0.605N P=0.757 (e) P=0.752N |P=0.003 ** P=0.304N P=0.163 P=0.016 * | |COCH-ARM / FISHERS | P=0.616N P=0.753N P=0.500N P=0.753N |P=0.003 ** P=0.274N P=0.109 P=0.018 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 19/50 (38%) 20/50 (40%) 13/50 (26%) |10/50 (20%) 10/50 (20%) 12/50 (24%) 12/50 (24%) | |POLY-3 RATE (b) | 14/49.92 19/48.13 20/47.30 13/49.55 |10/46.92 10/47.53 12/48.93 12/47.97 | |POLY-3 PERCENT (g) | 28.0% 39.5% 42.3% 26.2% |21.3% 21.0% 24.5% 25.0% | |TERMINAL (d) | 12/47 (26%) 19/46 (41%) 15/39 (39%) 13/49 (27%) |7/41 (17%) 4/37 (11%) 10/44 (23%) 9/43 (21%) | |FIRST INCIDENCE | 100 728 (T) 365 728 (T) |609 325 425 379 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.329N P=0.182 P=0.063 P=0.454N |P=0.404 P=0.527 P=0.474 P=0.449 | |POLY 3 | P=0.364N P=0.163 P=0.103 P=0.509N |P=0.345 P=0.586N P=0.448 P=0.427 | |POLY 1.5 | P=0.359N P=0.170 P=0.119 P=0.505N |P=0.333 P=0.587N P=0.434 P=0.416 | |POLY 6 | P=0.368N P=0.154 P=0.087 P=0.513N |P=0.358 P=0.593N P=0.458 P=0.436 | |LOGISTIC REGRESSION| P=0.380N P=0.199 P=0.202 P=0.574N |P=0.319 P=0.588N P=0.374 P=0.407 | |COCH-ARM / FISHERS | P=0.361N P=0.198 P=0.146 P=0.500N |P=0.322 P=0.598N P=0.405 P=0.405 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |35/49 (71%) 30/50 (60%) 36/49 (73%) 33/50 (66%) | |POLY-3 RATE (b) | |35/45.24 30/47.39 36/47.96 33/47.72 | |POLY-3 PERCENT (g) | |77.4% 63.3% 75.1% 69.2% | |TERMINAL (d) | |34/41 (83%) 23/37 (62%) 34/44 (77%) 31/43 (72%) | |FIRST INCIDENCE | |693 551 425 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.278N P=0.423N P=0.457N P=0.272N | |POLY 3 | |P=0.383N P=0.098N P=0.493N P=0.249N | |POLY 1.5 | |P=0.421N P=0.121N P=0.564N P=0.291N | |POLY 6 | |P=0.343N P=0.080N P=0.424N P=0.209N | |LOGISTIC REGRESSION| |P=0.440N P=0.166N P=0.534N P=0.315N | |COCH-ARM / FISHERS | |P=0.479N P=0.162N P=0.500 P=0.358N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Epididymis | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | | |POLY-3 RATE (b) | 3/48.41 0/48.13 2/44.90 2/49.55 | | |POLY-3 PERCENT (g) | 6.2% 0.0% 4.5% 4.0% | | |TERMINAL (d) | 3/47 (6%) 0/46 (0%) 2/39 (5%) 2/49 (4%) | | |FIRST INCIDENCE | 728 (T) --- 728 (T) 728 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.563N P=0.125N P=0.585N P=0.481N | | |POLY 3 | P=0.573N P=0.120N P=0.534N P=0.489N | | |POLY 1.5 | P=0.572N P=0.120N P=0.518N P=0.490N | | |POLY 6 | P=0.572N P=0.121N P=0.553N P=0.489N | | |LOGISTIC REGRESSION| P=0.563N (e) P=0.585N P=0.481N | | |COCH-ARM / FISHERS | P=0.578N P=0.121N P=0.500N P=0.500N | | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Esophagus | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 4/50 (8%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 2/48.92 2/48.69 4/47.54 0/49.55 |1/46.82 2/45.70 1/48.14 1/46.57 | |POLY-3 PERCENT (g) | 4.1% 4.1% 8.4% 0.0% |2.1% 4.4% 2.1% 2.2% | |TERMINAL (d) | 1/47 (2%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 572 594 365 --- |456 663 638 726 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.233N P=0.690 P=0.313 P=0.233N |P=0.517N P=0.486 P=0.753N P=0.760N | |POLY 3 | P=0.226N P=0.692 P=0.324 P=0.235N |P=0.529N P=0.492 P=0.754N P=0.759 | |POLY 1.5 | P=0.225N P=0.692 P=0.334 P=0.234N |P=0.531N P=0.495 P=0.757N P=0.758 | |POLY 6 | P=0.227N P=0.691 P=0.312 P=0.235N |P=0.526N P=0.486 P=0.751N P=0.760N | |LOGISTIC REGRESSION| P=0.354N P=0.690N P=0.414 P=0.277N |P=0.494N P=0.523 P=0.678 P=0.726N | |COCH-ARM / FISHERS | P=0.232N P=0.691N P=0.339 P=0.247N |P=0.530N P=0.500 P=0.753N P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Gallbladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 2/50 (4%) 4/49 (8%) |6/50 (12%) 5/50 (10%) 5/50 (10%) 3/50 (6%) | |POLY-3 RATE (b) | 4/48.41 2/48.13 2/44.90 4/48.55 |6/46.06 5/45.42 5/47.80 3/46.54 | |POLY-3 PERCENT (g) | 8.3% 4.2% 4.5% 8.2% |13.0% 11.0% 10.5% 6.5% | |TERMINAL (d) | 4/47 (9%) 2/46 (4%) 2/39 (5%) 4/48 (8%) |6/41 (15%) 5/37 (14%) 5/44 (11%) 3/43 (7%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.505 P=0.347N P=0.426N P=0.632N |P=0.156N P=0.572N P=0.450N P=0.219N | |POLY 3 | P=0.496 P=0.340N P=0.373N P=0.641N |P=0.187N P=0.510N P=0.474N P=0.237N | |POLY 1.5 | P=0.497 P=0.339N P=0.356N P=0.642N |P=0.194N P=0.505N P=0.484N P=0.242N | |POLY 6 | P=0.496 P=0.343N P=0.393N P=0.640N |P=0.179N P=0.520N P=0.465N P=0.231N | |LOGISTIC REGRESSION| P=0.505 P=0.347N P=0.426N P=0.632N |P=0.156N P=0.572N P=0.450N P=0.219N | |COCH-ARM / FISHERS | P=0.489 P=0.339N P=0.339N P=0.631 |P=0.196N P=0.500N P=0.500N P=0.243N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/4 (0%) 0/4 (0%) 0/1 (0%) 0/3 (0%) |0/1 (0%) 1/4 (25%) 2/5 (40%) 0/0 (0%) | |POLY-3 RATE (b) | 0/4.00 0/4.00 0/1.00 0/3.00 |0/1.00 1/3.63 2/5.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 27.6% 40.0% 0.0% | |TERMINAL (d) | 0/4 (0%) 0/4 (0%) 0/1 (0%) 0/3 (0%) |0/1 (0%) 1/3 (33%) 2/5 (40%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 733 (T) 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.627 P=0.718 P=0.638 (e) | |POLY 3 | (e) (e) (e) (e) |(e) P=0.742 P=0.631 (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) P=0.745 P=0.631 (e) | |POLY 6 | (e) (e) (e) (e) |(e) P=0.736 P=0.631 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.718 P=0.638 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.582 P=0.800 P=0.667 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 2/48.41 1/48.13 2/46.04 1/50.00 |1/46.19 1/45.46 0/47.80 2/47.08 | |POLY-3 PERCENT (g) | 4.1% 2.1% 4.3% 2.0% |2.2% 2.2% 0.0% 4.3% | |TERMINAL (d) | 2/47 (4%) 1/46 (2%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | 728 (T) 728 (T) 533 596 |698 723 --- 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.437N P=0.508N P=0.649 P=0.486N |P=0.386 P=0.744 P=0.491N P=0.511 | |POLY 3 | P=0.434N P=0.502N P=0.676 P=0.489N |P=0.374 P=0.757 P=0.493N P=0.507 | |POLY 1.5 | P=0.436N P=0.501N P=0.685 P=0.491N |P=0.370 P=0.759 P=0.496N P=0.502 | |POLY 6 | P=0.432N P=0.504N P=0.665 P=0.486N |P=0.379 P=0.753 P=0.491N P=0.512 | |LOGISTIC REGRESSION| P=0.508N P=0.508N P=0.694N P=0.540N |P=0.374 P=0.762 P=0.509N P=0.514 | |COCH-ARM / FISHERS | P=0.444N P=0.500N P=0.691N P=0.500N |P=0.366 P=0.753N P=0.500N P=0.500 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.41 1/48.13 1/45.58 0/49.55 |1/46.80 2/45.42 1/47.80 2/47.40 | |POLY-3 PERCENT (g) | 0.0% 2.1% 2.2% 0.0% |2.1% 4.4% 2.1% 4.2% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 2/37 (5%) 1/44 (2%) 1/43 (2%) | |FIRST INCIDENCE | --- 728 (T) 498 --- |463 733 (T) 733 (T) 379 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.587N P=0.496 P=0.500 (e) |P=0.465 P=0.476 P=0.752N P=0.501 | |POLY 3 | P=0.589N P=0.499 P=0.488 (e) |P=0.453 P=0.490 P=0.756N P=0.504 | |POLY 1.5 | P=0.589N P=0.499 P=0.494 (e) |P=0.448 P=0.494 P=0.758N P=0.501 | |POLY 6 | P=0.590N P=0.498 P=0.481 (e) |P=0.459 P=0.483 P=0.754N P=0.508 | |LOGISTIC REGRESSION| P=0.663N P=0.496 P=0.436 (e) |P=0.494 P=0.515 P=0.701 P=0.627 | |COCH-ARM / FISHERS | P=0.595N P=0.500 P=0.500 (e) |P=0.444 P=0.500 P=0.753N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 5/50 (10%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 5/47.31 0/49.55 |1/46.82 0/45.42 1/48.14 1/46.57 | |POLY-3 PERCENT (g) | 0.0% 0.0% 10.6% 0.0% |2.1% 0.0% 2.1% 2.2% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | --- --- 365 --- |456 --- 638 726 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.475 (e) P=0.031 * (e) |P=0.546 P=0.504N P=0.753N P=0.760N | |POLY 3 | P=0.492 (e) P=0.029 * (e) |P=0.542 P=0.506N P=0.754N P=0.759 | |POLY 1.5 | P=0.488 (e) P=0.030 * (e) |P=0.539 P=0.504N P=0.757N P=0.758 | |POLY 6 | P=0.496 (e) P=0.027 * (e) |P=0.548 P=0.510N P=0.751N P=0.760N | |LOGISTIC REGRESSION| P=0.309 (e) P=0.023 * (e) |P=0.598 P=0.396N P=0.678 P=0.726N | |COCH-ARM / FISHERS | P=0.469 (e) P=0.028 * (e) |P=0.539 P=0.500N P=0.753N P=0.753N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart: Artery | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 1/44.90 2/49.55 |1/46.80 0/45.42 0/47.80 2/47.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.0% |2.1% 0.0% 0.0% 4.3% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 1/39 (3%) 2/49 (4%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) |463 --- --- 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.079 (e) P=0.463 P=0.248 |P=0.254 P=0.500N P=0.500N P=0.506 | |POLY 3 | P=0.073 (e) P=0.485 P=0.243 |P=0.251 P=0.506N P=0.496N P=0.502 | |POLY 1.5 | P=0.073 (e) P=0.492 P=0.242 |P=0.248 P=0.504N P=0.497N P=0.499 | |POLY 6 | P=0.074 (e) P=0.477 P=0.243 |P=0.255 P=0.510N P=0.494N P=0.506 | |LOGISTIC REGRESSION| (e) (e) P=0.463 P=0.248 |P=0.308 P=0.402N P=0.603N P=0.571 | |COCH-ARM / FISHERS | P=0.070 (e) P=0.500 P=0.247 |P=0.246 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 3/50 (6%) 4/50 (8%) |3/50 (6%) 4/50 (8%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 4/48.41 5/48.13 3/44.90 4/49.55 |3/46.06 4/45.42 0/47.80 2/46.54 | |POLY-3 PERCENT (g) | 8.3% 10.4% 6.7% 8.1% |6.5% 8.8% 0.0% 4.3% | |TERMINAL (d) | 4/47 (9%) 5/46 (11%) 3/39 (8%) 4/49 (8%) |3/41 (7%) 4/37 (11%) 0/44 (0%) 2/43 (5%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) 733 (T) --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.480N P=0.487 P=0.601N P=0.620N |P=0.231N P=0.444 P=0.109N P=0.478N | |POLY 3 | P=0.492N P=0.496 P=0.541N P=0.630N |P=0.256N P=0.492 P=0.112N P=0.495N | |POLY 1.5 | P=0.491N P=0.498 P=0.521N P=0.631N |P=0.260N P=0.496 P=0.115N P=0.499N | |POLY 6 | P=0.493N P=0.493 P=0.563N P=0.629N |P=0.252N P=0.484 P=0.110N P=0.490N | |LOGISTIC REGRESSION| P=0.480N P=0.487 P=0.601N P=0.620N |P=0.231N P=0.444 (e) P=0.478N | |COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.500N P=0.643N |P=0.263N P=0.500 P=0.121N P=0.500N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 3/50 (6%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/48.41 0/48.13 3/44.90 3/49.55 |0/46.06 0/45.42 0/47.80 1/46.54 | |POLY-3 PERCENT (g) | 6.2% 0.0% 6.7% 6.1% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 3/47 (6%) 0/46 (0%) 3/39 (8%) 3/49 (6%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | 728 (T) --- 728 (T) 728 (T) |--- --- --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.403 P=0.125N P=0.574 P=0.643N |P=0.210 (e) (e) P=0.510 | |POLY 3 | P=0.398 P=0.120N P=0.627 P=0.651N |P=0.201 (e) (e) P=0.502 | |POLY 1.5 | P=0.397 P=0.120N P=0.644 P=0.652N |P=0.200 (e) (e) P=0.500 | |POLY 6 | P=0.399 P=0.121N P=0.607 P=0.650N |P=0.204 (e) (e) P=0.504 | |LOGISTIC REGRESSION| P=0.403 (e) P=0.574 P=0.643N |(e) (e) (e) P=0.510 | |COCH-ARM / FISHERS | P=0.386 P=0.121N P=0.661N P=0.661N |P=0.198 (e) (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 5/48.41 2/48.13 2/44.90 0/49.55 |1/46.06 0/45.42 0/47.80 2/47.08 | |POLY-3 PERCENT (g) | 10.3% 4.2% 4.5% 0.0% |2.2% 0.0% 0.0% 4.3% | |TERMINAL (d) | 5/47 (11%) 2/46 (4%) 2/39 (5%) 0/49 (0%) |1/41 (2%) 0/37 (0%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) --- |733 (T) --- --- 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.023N* P=0.226N P=0.298N P=0.030N* |P=0.262 P=0.520N P=0.486N P=0.513 | |POLY 3 | P=0.020N* P=0.219N P=0.248N P=0.029N* |P=0.251 P=0.503N P=0.493N P=0.508 | |POLY 1.5 | P=0.020N* P=0.218N P=0.233N P=0.029N* |P=0.248 P=0.501N P=0.495N P=0.503 | |POLY 6 | P=0.020N* P=0.221N P=0.267N P=0.029N* |P=0.256 P=0.506N P=0.490N P=0.514 | |LOGISTIC REGRESSION| P=0.023N* P=0.226N P=0.298N (e) |P=0.253 (e) (e) P=0.508 | |COCH-ARM / FISHERS | P=0.022N* P=0.218N P=0.218N P=0.028N* |P=0.246 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 42/50 (84%) 40/50 (80%) 44/50 (88%) |9/50 (18%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 29/48.92 42/48.13 40/46.70 44/49.55 |9/49.41 0/48.13 0/44.90 0/49.55 | |POLY-3 PERCENT (g) | 59.3% 87.3% 85.7% 88.8% |18.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 28/47 (60%) 42/46 (91%) 36/39 (92%) 44/49 (90%) |8/47 (17%) 0/46 (0%) 0/39 (0%) 0/49 (0%) | |FIRST INCIDENCE | 572 728 (T) 498 728 (T) |100 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** P=0.002 ** P<0.001 ** P=0.002 ** |P<0.001N** P=0.003N** P=0.006N** P=0.002N** | |POLY 3 | P<0.001 ** P<0.001 ** P=0.003 ** P<0.001 ** |P<0.001N** P=0.002N** P=0.003N** P=0.002N** | |POLY 1.5 | P<0.001 ** P=0.002 ** P=0.006 ** P<0.001 ** |P<0.001N** P=0.002N** P=0.002N** P=0.002N** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001N** P=0.002N** P=0.004N** P=0.002N** | |LOGISTIC REGRESSION| P<0.001 ** P=0.003 ** P=0.003 ** P<0.001 ** |P<0.001N** P=0.002N** P=0.002N** P=0.004N** | |COCH-ARM / FISHERS | P=0.002 ** P=0.004 ** P=0.015 * P<0.001 ** |P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 2/44.90 1/49.55 |1/46.06 1/45.52 1/47.80 1/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 2.0% |2.2% 2.2% 2.1% 2.2% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 2/39 (5%) 1/49 (2%) |1/41 (2%) 0/37 (0%) 1/44 (2%) 1/43 (2%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) |733 (T) 708 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.259 (e) P=0.198 P=0.508 |P=0.608N P=0.743 P=0.746N P=0.751N | |POLY 3 | P=0.258 (e) P=0.221 P=0.505 |P=0.627N P=0.758 P=0.752N P=0.758N | |POLY 1.5 | P=0.256 (e) P=0.229 P=0.504 |P=0.630N P=0.759 P=0.755N P=0.760N | |POLY 6 | P=0.260 (e) P=0.212 P=0.505 |P=0.623N P=0.755 P=0.749N P=0.756N | |LOGISTIC REGRESSION| (e) (e) P=0.198 P=0.508 |P=0.624N P=0.759 P=0.746N P=0.751N | |COCH-ARM / FISHERS | P=0.246 (e) P=0.247 P=0.500 |P=0.634 P=0.753N P=0.753N P=0.753N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.41 1/48.13 3/44.90 2/49.55 |1/46.48 1/45.42 3/47.80 1/46.54 | |POLY-3 PERCENT (g) | 0.0% 2.1% 6.7% 4.0% |2.2% 2.2% 6.3% 2.2% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 3/39 (8%) 2/49 (4%) |0/41 (0%) 1/37 (3%) 3/44 (7%) 1/43 (2%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) 728 (T) |609 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.178 P=0.496 P=0.091 P=0.248 |P=0.583 P=0.747 P=0.330 P=0.755N | |POLY 3 | P=0.173 P=0.499 P=0.106 P=0.243 |P=0.560 P=0.755 P=0.316 P=0.760N | |POLY 1.5 | P=0.172 P=0.499 P=0.112 P=0.242 |P=0.555 P=0.758 P=0.312 P=0.760 | |POLY 6 | P=0.175 P=0.498 P=0.099 P=0.243 |P=0.566 P=0.751 P=0.318 P=0.759N | |LOGISTIC REGRESSION| (e) P=0.496 P=0.091 P=0.248 |P=0.556 P=0.758N P=0.292 P=0.757N | |COCH-ARM / FISHERS | P=0.163 P=0.500 P=0.121 P=0.247 |P=0.556 P=0.753N P=0.309 P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 44/50 (88%) 49/50 (98%) 45/50 (90%) 46/50 (92%) |4/50 (8%) 1/50 (2%) 2/50 (4%) 6/50 (12%) | |POLY-3 RATE (b) | 44/49.00 49/49.00 45/47.56 46/49.55 |4/47.00 1/45.42 2/47.83 6/46.54 | |POLY-3 PERCENT (g) | 89.8% 100.0% 94.6% 92.8% |8.5% 2.2% 4.2% 12.9% | |TERMINAL (d) | 42/47 (89%) 46/46 (100%) 38/39 (97%) 46/49 (94%) |2/41 (5%) 1/37 (3%) 1/44 (2%) 6/43 (14%) | |FIRST INCIDENCE | 572 594 533 728 (T) |570 733 (T) 726 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.431N P=0.056 P=0.019 * P=0.610 |P=0.186 P=0.202N P=0.313N P=0.397 | |POLY 3 | P=0.574 P=0.031 * P=0.299 P=0.428 |P=0.157 P=0.189N P=0.329N P=0.364 | |POLY 1.5 | P=0.555N P=0.030 * P=0.411 P=0.448 |P=0.154 P=0.185N P=0.332N P=0.364 | |POLY 6 | P=0.514 P=0.031 * P=0.199 P=0.396 |P=0.162 P=0.198N P=0.328N P=0.364 | |LOGISTIC REGRESSION| P=0.514N P=0.034 * P=0.226 P=0.505 |P=0.154 P=0.173N P=0.375N P=0.370 | |COCH-ARM / FISHERS | P=0.500 P=0.056 P=0.500 P=0.370 |P=0.154 P=0.181N P=0.339N P=0.370 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 47/50 (94%) 46/50 (92%) 38/50 (76%) 42/50 (84%) |11/50 (22%) 4/50 (8%) 12/50 (24%) 8/50 (16%) | |POLY-3 RATE (b) | 47/49.92 46/48.44 38/45.45 42/49.55 |11/47.69 4/45.79 12/47.80 8/47.23 | |POLY-3 PERCENT (g) | 94.2% 95.0% 83.6% 84.8% |23.1% 8.7% 25.1% 16.9% | |TERMINAL (d) | 45/47 (96%) 45/46 (98%) 37/39 (95%) 42/49 (86%) |8/41 (20%) 3/37 (8%) 12/44 (27%) 6/43 (14%) | |FIRST INCIDENCE | 100 644 561 728 (T) |463 628 733 (T) 587 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.006N** P=0.656N P=0.456N P=0.034N* |P=0.415N P=0.071N P=0.567 P=0.283N | |POLY 3 | P=0.032N* P=0.608 P=0.073N P=0.112N |P=0.477N P=0.052N P=0.503 P=0.313N | |POLY 1.5 | P=0.034N* P=0.640 P=0.032N* P=0.106N |P=0.488N P=0.049N* P=0.501 P=0.316N | |POLY 6 | P=0.032N* P=0.564 P=0.183N P=0.118N |P=0.457N P=0.057N P=0.504 P=0.305N | |LOGISTIC REGRESSION| P=0.018N* P=0.513N P=0.023N* P=0.094N |P=0.488N P=0.043N* P=0.483 P=0.300N | |COCH-ARM / FISHERS | P=0.050N P=0.500N P=0.011N* P=0.100N |P=0.488N P=0.045N* P=0.500 P=0.306N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 5/50 (10%) 8/50 (16%) 9/50 (18%) |25/50 (50%) 30/50 (60%) 22/50 (44%) 32/50 (64%) | |POLY-3 RATE (b) | 7/48.41 5/48.13 8/44.90 9/49.55 |25/47.88 30/48.65 22/48.13 32/47.08 | |POLY-3 PERCENT (g) | 14.5% 10.4% 17.8% 18.2% |52.2% 61.7% 45.7% 68.0% | |TERMINAL (d) | 7/47 (15%) 5/46 (11%) 8/39 (21%) 9/49 (18%) |20/41 (49%) 22/37 (60%) 21/44 (48%) 31/43 (72%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |456 325 642 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.265 P=0.394N P=0.346 P=0.428 |P=0.316 P=0.132 P=0.250N P=0.176 | |POLY 3 | P=0.252 P=0.384N P=0.437 P=0.413 |P=0.126 P=0.231 P=0.332N P=0.084 | |POLY 1.5 | P=0.252 P=0.382N P=0.467 P=0.411 |P=0.131 P=0.224 P=0.338N P=0.088 | |POLY 6 | P=0.253 P=0.387N P=0.403 P=0.414 |P=0.124 P=0.233 P=0.326N P=0.083 | |LOGISTIC REGRESSION| P=0.265 P=0.394N P=0.346 P=0.428 |P=0.166 P=0.214 P=0.317N P=0.112 | |COCH-ARM / FISHERS | P=0.238 P=0.380N P=0.500 P=0.393 |P=0.163 P=0.211 P=0.344N P=0.113 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 1/50 (2%) 0/50 (0%) |4/49 (8%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 3/48.41 3/48.13 1/44.90 0/49.55 |4/45.21 2/45.42 1/47.80 0/46.54 | |POLY-3 PERCENT (g) | 6.2% 6.2% 2.2% 0.0% |8.9% 4.4% 2.1% 0.0% | |TERMINAL (d) | 3/47 (6%) 3/46 (7%) 1/39 (3%) 0/49 (0%) |4/41 (10%) 2/37 (5%) 1/44 (2%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) --- |733 (T) 733 (T) 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.054N P=0.653 P=0.374N P=0.114N |P=0.025N* P=0.385N P=0.159N P=0.057N | |POLY 3 | P=0.051N P=0.659 P=0.333N P=0.115N |P=0.027N* P=0.335N P=0.162N P=0.057N | |POLY 1.5 | P=0.051N P=0.660 P=0.320N P=0.115N |P=0.027N* P=0.332N P=0.166N P=0.058N | |POLY 6 | P=0.051N P=0.657 P=0.349N P=0.115N |P=0.026N* P=0.343N P=0.159N P=0.055N | |LOGISTIC REGRESSION| P=0.054N P=0.653 P=0.374N (e) |P=0.025N* P=0.385N P=0.159N (e) | |COCH-ARM / FISHERS | P=0.052N P=0.661N P=0.309N P=0.121N |P=0.028N* P=0.329N P=0.175N P=0.056N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 2/50 (4%) 1/50 (2%) |1/49 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.41 3/48.13 2/44.90 1/49.55 |1/45.21 2/45.64 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 2.1% 6.2% 4.5% 2.0% |2.2% 4.4% 0.0% 0.0% | |TERMINAL (d) | 1/47 (2%) 3/46 (7%) 2/39 (5%) 1/49 (2%) |1/41 (2%) 1/37 (3%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) 673 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.462N P=0.298 P=0.435 P=0.752N |P=0.177N P=0.468 P=0.486N P=0.490N | |POLY 3 | P=0.466N P=0.304 P=0.474 P=0.755N |P=0.183N P=0.503 P=0.489N P=0.494N | |POLY 1.5 | P=0.466N P=0.304 P=0.486 P=0.756N |P=0.184N P=0.505 P=0.491N P=0.496N | |POLY 6 | P=0.467N P=0.302 P=0.459 P=0.755N |P=0.181N P=0.499 P=0.487N P=0.492N | |LOGISTIC REGRESSION| P=0.462N P=0.298 P=0.435 P=0.752N |P=0.184N P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.474N P=0.309 P=0.500 P=0.753N |P=0.185N P=0.508 P=0.495N P=0.495N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 4/50 (8%) 2/50 (4%) |4/49 (8%) 8/50 (16%) 4/50 (8%) 7/50 (14%) | |POLY-3 RATE (b) | 3/48.41 4/48.59 4/44.90 2/49.55 |4/46.11 8/45.99 4/47.80 7/46.54 | |POLY-3 PERCENT (g) | 6.2% 8.2% 8.9% 4.0% |8.7% 17.4% 8.4% 15.0% | |TERMINAL (d) | 3/47 (6%) 3/46 (7%) 4/39 (10%) 2/49 (4%) |2/41 (5%) 7/37 (19%) 4/44 (9%) 7/43 (16%) | |FIRST INCIDENCE | 728 (T) 594 728 (T) 728 (T) |456 551 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.355N P=0.492 P=0.399 P=0.481N |P=0.399 P=0.147 P=0.611N P=0.286 | |POLY 3 | P=0.358N P=0.502 P=0.459 P=0.489N |P=0.348 P=0.175 P=0.623N P=0.267 | |POLY 1.5 | P=0.358N P=0.501 P=0.479 P=0.490N |P=0.346 P=0.181 P=0.626N P=0.266 | |POLY 6 | P=0.358N P=0.502 P=0.436 P=0.489N |P=0.352 P=0.166 P=0.621N P=0.267 | |LOGISTIC REGRESSION| P=0.361N P=0.500 P=0.399 P=0.481N |P=0.352 P=0.191 P=0.625 P=0.273 | |COCH-ARM / FISHERS | P=0.367N P=0.500 P=0.500 P=0.500N |P=0.351 P=0.188 P=0.631N P=0.274 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |6/49 (12%) 3/50 (6%) 2/50 (4%) 5/50 (10%) | |POLY-3 RATE (b) | 0/48.41 1/48.24 1/45.19 0/49.55 |6/46.10 3/45.89 2/47.80 5/47.08 | |POLY-3 PERCENT (g) | 0.0% 2.1% 2.2% 0.0% |13.0% 6.5% 4.2% 10.6% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |4/41 (10%) 1/37 (3%) 2/44 (5%) 4/43 (9%) | |FIRST INCIDENCE | --- 701 652 --- |463 628 733 (T) 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.590N P=0.496 P=0.478 (e) |P=0.457N P=0.283N P=0.121N P=0.475N | |POLY 3 | P=0.590N P=0.499 P=0.486 (e) |P=0.482N P=0.244N P=0.122N P=0.485N | |POLY 1.5 | P=0.590N P=0.500 P=0.493 (e) |P=0.487N P=0.240N P=0.124N P=0.489N | |POLY 6 | P=0.590N P=0.499 P=0.479 (e) |P=0.474N P=0.252N P=0.121N P=0.480N | |LOGISTIC REGRESSION| P=0.616N P=0.501 P=0.502 (e) |P=0.488N P=0.225N P=0.143N P=0.480N | |COCH-ARM / FISHERS | P=0.595N P=0.500 P=0.500 (e) |P=0.490N P=0.233N P=0.128N P=0.486N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 33/50 (66%) 34/50 (68%) 28/50 (56%) 27/50 (54%) |42/49 (86%) 36/50 (72%) 38/50 (76%) 41/50 (82%) | |POLY-3 RATE (b) | 33/48.92 34/48.13 28/45.58 27/49.55 |42/47.80 36/47.22 38/48.13 41/49.11 | |POLY-3 PERCENT (g) | 67.5% 70.6% 61.4% 54.5% |87.9% 76.2% 79.0% 83.5% | |TERMINAL (d) | 32/47 (68%) 34/46 (74%) 27/39 (69%) 27/49 (55%) |37/41 (90%) 30/37 (81%) 37/44 (84%) 37/43 (86%) | |FIRST INCIDENCE | 572 728 (T) 498 728 (T) |463 575 642 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.047N* P=0.438 P=0.540 P=0.101N |P=0.289N P=0.375N P=0.075N P=0.338N | |POLY 3 | P=0.060N P=0.452 P=0.344N P=0.133N |P=0.468N P=0.104N P=0.177N P=0.370N | |POLY 1.5 | P=0.059N P=0.472 P=0.268N P=0.131N |P=0.491N P=0.091N P=0.170N P=0.380N | |POLY 6 | P=0.061N P=0.422 P=0.449N P=0.137N |P=0.452N P=0.125N P=0.191N P=0.371N | |LOGISTIC REGRESSION| P=0.058N P=0.483 P=0.393N P=0.123N |P=0.537N P=0.075N P=0.100N P=0.414N | |COCH-ARM / FISHERS | P=0.078N P=0.500 P=0.206N P=0.154N |P=0.541N P=0.077N P=0.166N P=0.410N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) 3/50 (6%) 6/50 (12%) |1/49 (2%) 3/50 (6%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 5/48.41 3/48.13 3/44.90 6/49.55 |1/45.21 3/45.42 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 10.3% 6.2% 6.7% 12.1% |2.2% 6.6% 0.0% 0.0% | |TERMINAL (d) | 5/47 (11%) 3/46 (7%) 3/39 (8%) 6/49 (12%) |1/41 (2%) 3/37 (8%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) 733 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.373 P=0.368N P=0.462N P=0.529 |P=0.139N P=0.269 P=0.486N P=0.490N | |POLY 3 | P=0.359 P=0.360N P=0.399N P=0.516 |P=0.146N P=0.307 P=0.489N P=0.494N | |POLY 1.5 | P=0.359 P=0.359N P=0.378N P=0.515 |P=0.147N P=0.310 P=0.491N P=0.496N | |POLY 6 | P=0.359 P=0.363N P=0.423N P=0.517 |P=0.145N P=0.300 P=0.487N P=0.492N | |LOGISTIC REGRESSION| P=0.373 P=0.368N P=0.462N P=0.529 |P=0.139N P=0.269 (e) (e) | |COCH-ARM / FISHERS | P=0.350 P=0.357N P=0.357N P=0.500 |P=0.150N P=0.316 P=0.495N P=0.495N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) 4/50 (8%) 3/50 (6%) |2/49 (4%) 2/50 (4%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 6/48.92 4/48.44 4/45.29 3/49.55 |2/45.21 2/46.03 1/47.80 3/47.40 | |POLY-3 PERCENT (g) | 12.3% 8.3% 8.8% 6.1% |4.4% 4.3% 2.1% 6.3% | |TERMINAL (d) | 5/47 (11%) 3/46 (7%) 2/39 (5%) 3/49 (6%) |2/41 (5%) 0/37 (0%) 1/44 (2%) 2/43 (5%) | |FIRST INCIDENCE | 572 644 652 728 (T) |733 (T) 551 733 (T) 379 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.206N P=0.383N P=0.481N P=0.226N |P=0.433 P=0.671 P=0.475N P=0.515 | |POLY 3 | P=0.206N P=0.376N P=0.419N P=0.237N |P=0.423 P=0.687N P=0.481N P=0.522 | |POLY 1.5 | P=0.204N P=0.374N P=0.396N P=0.236N |P=0.417 P=0.686N P=0.485N P=0.516 | |POLY 6 | P=0.208N P=0.380N P=0.445N P=0.239N |P=0.430 P=0.691N P=0.477N P=0.527 | |LOGISTIC REGRESSION| P=0.209N P=0.368N P=0.367N P=0.253N |P=0.431 P=0.684N P=0.475N P=0.529 | |COCH-ARM / FISHERS | P=0.208N P=0.370N P=0.370N P=0.243N |P=0.410 P=0.684N P=0.492N P=0.510 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |3/49 (6%) 4/50 (8%) 2/50 (4%) 4/50 (8%) | |POLY-3 RATE (b) | 0/48.41 1/48.13 1/44.90 1/49.55 |3/45.64 4/45.46 2/47.80 4/47.08 | |POLY-3 PERCENT (g) | 0.0% 2.1% 2.2% 2.0% |6.6% 8.8% 4.2% 8.5% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 1/39 (3%) 1/49 (2%) |2/41 (5%) 3/37 (8%) 2/44 (5%) 3/43 (7%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) 728 (T) |609 723 733 (T) 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.395 P=0.496 P=0.463 P=0.508 |P=0.524 P=0.453 P=0.471N P=0.520 | |POLY 3 | P=0.395 P=0.499 P=0.485 P=0.505 |P=0.501 P=0.498 P=0.479N P=0.517 | |POLY 1.5 | P=0.394 P=0.499 P=0.492 P=0.504 |P=0.494 P=0.504 P=0.483N P=0.512 | |POLY 6 | P=0.396 P=0.498 P=0.477 P=0.505 |P=0.509 P=0.486 P=0.477N P=0.522 | |LOGISTIC REGRESSION| (e) P=0.496 P=0.463 P=0.508 |P=0.490 P=0.507 P=0.497N P=0.515 | |COCH-ARM / FISHERS | P=0.384 P=0.500 P=0.500 P=0.500 |P=0.490 P=0.511 P=0.490N P=0.511 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/49 (2%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/44.90 1/49.55 |1/45.21 2/45.52 0/47.80 1/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.0% |2.2% 4.4% 0.0% 2.2% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 1/49 (2%) |1/41 (2%) 1/37 (3%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | --- --- --- 728 (T) |733 (T) 708 --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.209 (e) (e) P=0.508 |P=0.474N P=0.471 P=0.486N P=0.751N | |POLY 3 | P=0.202 (e) (e) P=0.505 |P=0.491N P=0.502 P=0.489N P=0.754N | |POLY 1.5 | P=0.202 (e) (e) P=0.504 |P=0.493N P=0.505 P=0.491N P=0.756N | |POLY 6 | P=0.203 (e) (e) P=0.505 |P=0.489N P=0.497 P=0.487N P=0.752N | |LOGISTIC REGRESSION| (e) (e) (e) P=0.508 |P=0.486N P=0.497 (e) P=0.751N | |COCH-ARM / FISHERS | P=0.198 (e) (e) P=0.500 |P=0.495N P=0.508 P=0.495N P=0.747N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Portal | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 6/50 (12%) 8/50 (16%) 3/50 (6%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.41 6/48.13 8/44.90 3/49.55 |2/48.41 0/48.13 0/44.90 0/49.55 | |POLY-3 PERCENT (g) | 2.1% 12.5% 17.8% 6.1% |4.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/47 (2%) 6/46 (13%) 8/39 (21%) 3/49 (6%) |2/47 (4%) 0/46 (0%) 0/39 (0%) 0/49 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |728 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.424 P=0.056 P=0.008 ** P=0.321 |P=0.119N P=0.243N P=0.280N P=0.229N | |POLY 3 | P=0.424 P=0.055 P=0.011 * P=0.314 |P=0.116N P=0.239N P=0.254N P=0.232N | |POLY 1.5 | P=0.422 P=0.056 P=0.013 * P=0.313 |P=0.115N P=0.238N P=0.246N P=0.233N | |POLY 6 | P=0.427 P=0.055 P=0.009 ** P=0.315 |P=0.117N P=0.240N P=0.264N P=0.232N | |LOGISTIC REGRESSION| P=0.424 P=0.056 P=0.008 ** P=0.321 |P=0.119N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.401 P=0.056 P=0.015 * P=0.309 |P=0.115N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.41 1/48.13 3/44.90 1/50.00 |1/46.19 0/45.42 3/48.34 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 2.1% 6.7% 2.0% |2.2% 0.0% 6.2% 0.0% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 3/39 (8%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 2/44 (5%) 0/43 (0%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) 596 |698 --- 568 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.365 P=0.496 P=0.091 P=0.508 |P=0.481N P=0.514N P=0.328 P=0.495N | |POLY 3 | P=0.373 P=0.499 P=0.106 P=0.506 |P=0.494N P=0.503N P=0.322 P=0.498N | |POLY 1.5 | P=0.368 P=0.499 P=0.112 P=0.505 |P=0.499N P=0.502N P=0.316 P=0.500N | |POLY 6 | P=0.379 P=0.498 P=0.099 P=0.508 |P=0.486N P=0.507N P=0.328 P=0.497N | |LOGISTIC REGRESSION| P=0.343 P=0.496 P=0.091 P=0.412 |P=0.494N P=0.499N P=0.271 P=0.499N | |COCH-ARM / FISHERS | P=0.351 P=0.500 P=0.121 P=0.500 |P=0.500N P=0.500N P=0.309 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 0/50 (0%) 5/50 (10%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 2/48.41 7/48.13 0/44.90 5/49.55 |1/46.06 0/45.42 2/47.80 1/46.54 | |POLY-3 PERCENT (g) | 4.1% 14.5% 0.0% 10.1% |2.2% 0.0% 4.2% 2.2% | |TERMINAL (d) | 2/47 (4%) 7/46 (15%) 0/39 (0%) 5/49 (10%) |1/41 (2%) 0/37 (0%) 2/44 (5%) 1/43 (2%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- 728 (T) |733 (T) --- 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.410 P=0.076 P=0.280N P=0.234 |P=0.527 P=0.520N P=0.525 P=0.751N | |POLY 3 | P=0.392 P=0.078 P=0.254N P=0.227 |P=0.507 P=0.503N P=0.513 P=0.758N | |POLY 1.5 | P=0.394 P=0.079 P=0.246N P=0.226 |P=0.502 P=0.501N P=0.508 P=0.760N | |POLY 6 | P=0.389 P=0.077 P=0.264N P=0.227 |P=0.515 P=0.506N P=0.518 P=0.756N | |LOGISTIC REGRESSION| P=0.410 P=0.076 (e) P=0.234 |P=0.527 (e) P=0.525 P=0.751N | |COCH-ARM / FISHERS | P=0.390 P=0.080 P=0.247N P=0.218 |P=0.500 P=0.500N P=0.500 P=0.753N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/46 (0%) 2/46 (4%) 0/50 (0%) |1/49 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/47.92 0/45.59 2/41.91 0/49.55 |1/45.59 0/45.42 0/46.80 0/46.54 | |POLY-3 PERCENT (g) | 2.1% 0.0% 4.8% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/47 (2%) 0/44 (0%) 1/37 (3%) 0/49 (0%) |1/41 (2%) 0/37 (0%) 0/43 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) --- 652 --- |733 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.454N P=0.513N P=0.430 P=0.492N |P=0.297N P=0.520N P=0.490N P=0.490N | |POLY 3 | P=0.450N P=0.510N P=0.453 P=0.493N |P=0.301N P=0.501N P=0.495N P=0.496N | |POLY 1.5 | P=0.450N P=0.510N P=0.465 P=0.493N |P=0.302N P=0.499N P=0.497N P=0.497N | |POLY 6 | P=0.450N P=0.511N P=0.441 P=0.494N |P=0.299N P=0.505N P=0.493N P=0.495N | |LOGISTIC REGRESSION| P=0.460N (e) P=0.480 (e) |P=0.297N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.453N P=0.516N P=0.476 P=0.495N |P=0.304N P=0.495N P=0.500N P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/46 (0%) 1/46 (2%) 1/50 (2%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/47.92 0/45.59 1/41.63 1/49.55 |0/45.59 0/45.42 0/46.80 0/46.54 | |POLY-3 PERCENT (g) | 4.2% 0.0% 2.4% 2.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/47 (4%) 0/44 (0%) 1/37 (3%) 1/49 (2%) |0/41 (0%) 0/37 (0%) 0/43 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) --- 728 (T) 728 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.488N P=0.253N P=0.583N P=0.485N |(e) (e) (e) (e) | |POLY 3 | P=0.493N P=0.249N P=0.549N P=0.488N |(e) (e) (e) (e) | |POLY 1.5 | P=0.492N P=0.248N P=0.536N P=0.488N |(e) (e) (e) (e) | |POLY 6 | P=0.494N P=0.250N P=0.563N P=0.490N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.488N (e) P=0.583N P=0.485N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.490N P=0.263N P=0.524N P=0.492N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) |0/4 (0%) 2/5 (40%) 0/4 (0%) 1/1 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.90 0/0.00 |0/3.59 2/4.40 0/3.48 1/1.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 45.5% 0.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/3 (0%) 2/3 (67%) 0/1 (0%) 1/1 (100%) | |FIRST INCIDENCE | --- --- --- --- |--- 733 (T) --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.191 P=0.215 (e) P=0.282 | |POLY 3 | (e) (e) (e) (e) |P=0.162 P=0.251 (e) P<0.001 ** | |POLY 1.5 | (e) (e) (e) (e) |P=0.164 P=0.255 (e) P<0.001 ** | |POLY 6 | (e) (e) (e) (e) |P=0.161 P=0.248 (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.215 (e) P=0.282 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.207 P=0.278 (e) P=0.200 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) |3/4 (75%) 2/5 (40%) 1/4 (25%) 1/1 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.90 0/0.00 |3/3.59 2/4.40 1/3.48 1/1.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |83.6% 45.5% 28.7% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |3/3 (100%) 2/3 (67%) 1/1 (100%) 1/1 (100%) | |FIRST INCIDENCE | --- --- --- --- |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.755 P=0.500N P=1.000 P=1.000 | |POLY 3 | (e) (e) (e) (e) |P=0.642N P=0.352N P=0.215N P=0.903 | |POLY 1.5 | (e) (e) (e) (e) |P=0.618N P=0.358N P=0.225N P=0.827 | |POLY 6 | (e) (e) (e) (e) |P=0.684N P=0.337N P=0.208N P=0.991 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.755 P=0.500N P=1.000 P=1.000 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.598N P=0.357N P=0.243N P=0.800 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 3/48 (6%) 0/48 (0%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.92 3/46.69 0/44.04 3/50.00 |1/46.06 0/45.42 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 2.1% 6.4% 0.0% 6.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/46 (2%) 3/46 (7%) 0/39 (0%) 2/49 (4%) |1/41 (2%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- 596 |733 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.347 P=0.306 P=0.533N P=0.328 |P=0.296N P=0.520N P=0.486N P=0.490N | |POLY 3 | P=0.345 P=0.304 P=0.513N P=0.329 |P=0.304N P=0.503N P=0.493N P=0.498N | |POLY 1.5 | P=0.346 P=0.304 P=0.506N P=0.328 |P=0.304N P=0.501N P=0.495N P=0.500N | |POLY 6 | P=0.344 P=0.303 P=0.520N P=0.329 |P=0.303N P=0.506N P=0.490N P=0.496N | |LOGISTIC REGRESSION| P=0.337 P=0.306 (e) P=0.289 |P=0.296N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.341 P=0.308 P=0.500N P=0.324 |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 6/48 (13%) 0/48 (0%) 4/50 (8%) |5/50 (10%) 3/50 (6%) 4/50 (8%) 2/50 (4%) | |POLY-3 RATE (b) | 2/46.92 6/46.69 0/44.04 4/49.55 |5/46.06 3/45.42 4/48.34 2/46.54 | |POLY-3 PERCENT (g) | 4.3% 12.9% 0.0% 8.1% |10.9% 6.6% 8.3% 4.3% | |TERMINAL (d) | 2/46 (4%) 6/46 (13%) 0/39 (0%) 4/49 (8%) |5/41 (12%) 3/37 (8%) 3/44 (7%) 2/43 (5%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- 728 (T) |733 (T) 733 (T) 568 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.526 P=0.135 P=0.276N P=0.367 |P=0.169N P=0.413N P=0.458N P=0.198N | |POLY 3 | P=0.524 P=0.132 P=0.252N P=0.363 |P=0.192N P=0.364N P=0.470N P=0.212N | |POLY 1.5 | P=0.527 P=0.132 P=0.244N P=0.364 |P=0.197N P=0.361N P=0.481N P=0.216N | |POLY 6 | P=0.519 P=0.131 P=0.260N P=0.361 |P=0.184N P=0.372N P=0.458N P=0.207N | |LOGISTIC REGRESSION| P=0.526 P=0.135 (e) P=0.367 |P=0.192N P=0.413N P=0.496N P=0.198N | |COCH-ARM / FISHERS | P=0.523 P=0.134 P=0.247N P=0.359 |P=0.200N P=0.357N P=0.500N P=0.218N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 1/48 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.92 2/46.69 1/44.04 0/49.55 |0/46.06 0/45.42 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 4.3% 2.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/46 (0%) 2/46 (4%) 1/39 (3%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.449N P=0.239 P=0.467 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.448N P=0.236 P=0.487 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.446N P=0.237 P=0.494 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.450N P=0.236 P=0.480 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.239 P=0.467 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.450N P=0.247 P=0.500 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 2/48 (4%) 1/48 (2%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.92 2/46.69 1/44.04 3/49.55 |1/46.06 0/45.42 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 4.3% 4.3% 2.3% 6.1% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/46 (4%) 2/46 (4%) 1/39 (3%) 3/49 (6%) |1/41 (2%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.427 P=0.694 P=0.558N P=0.529 |P=0.296N P=0.520N P=0.486N P=0.490N | |POLY 3 | P=0.425 P=0.692 P=0.522N P=0.525 |P=0.304N P=0.503N P=0.493N P=0.498N | |POLY 1.5 | P=0.427 P=0.692 P=0.511N P=0.526 |P=0.304N P=0.501N P=0.495N P=0.500N | |POLY 6 | P=0.423 P=0.691 P=0.535N P=0.523 |P=0.303N P=0.506N P=0.490N P=0.496N | |LOGISTIC REGRESSION| P=0.427 P=0.694 P=0.558N P=0.529 |P=0.296N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.422 P=0.692N P=0.500N P=0.520 |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Degeneration Hyaline | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/48 (2%) 0/48 (0%) 0/50 (0%) |23/50 (46%) 25/50 (50%) 22/50 (44%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.92 1/46.69 0/44.04 0/49.55 |23/47.64 25/47.38 22/49.64 0/46.54 | |POLY-3 PERCENT (g) | 4.3% 2.1% 0.0% 0.0% |48.3% 52.8% 44.3% 0.0% | |TERMINAL (d) | 2/46 (4%) 1/46 (2%) 0/39 (0%) 0/49 (0%) |20/41 (49%) 19/37 (51%) 18/44 (41%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- --- |463 325 425 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.102N P=0.500N P=0.276N P=0.225N |P<0.001N** P=0.279 P=0.390N P<0.001N** | |POLY 3 | P=0.098N P=0.502N P=0.252N P=0.225N |P<0.001N** P=0.408 P=0.426N P<0.001N** | |POLY 1.5 | P=0.098N P=0.501N P=0.244N P=0.225N |P<0.001N** P=0.418 P=0.453N P<0.001N** | |POLY 6 | P=0.099N P=0.503N P=0.260N P=0.226N |P<0.001N** P=0.385 P=0.400N P<0.001N** | |LOGISTIC REGRESSION| P=0.102N P=0.500N (e) (e) |P<0.001N** P=0.417 P=0.527N P<0.001N** | |COCH-ARM / FISHERS | P=0.097N P=0.500N P=0.247N P=0.237N |P<0.001N** P=0.421 P=0.500N P<0.001N** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 3/48 (6%) 26/50 (52%) |0/50 (0%) 0/50 (0%) 8/50 (16%) 46/50 (92%) | |POLY-3 RATE (b) | 0/46.92 0/46.69 3/44.04 26/49.55 |0/46.06 0/45.42 8/47.80 46/48.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.8% 52.5% |0.0% 0.0% 16.7% 94.8% | |TERMINAL (d) | 0/46 (0%) 0/46 (0%) 3/39 (8%) 26/49 (53%) |0/41 (0%) 0/37 (0%) 8/44 (18%) 41/43 (95%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) |--- --- 733 (T) 379 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P=0.094 P<0.001 ** |P<0.001 ** (e) P=0.007 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.108 P<0.001 ** |P<0.001 ** (e) P=0.004 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.113 P<0.001 ** |P<0.001 ** (e) P=0.004 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.102 P<0.001 ** |P<0.001 ** (e) P=0.005 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) P=0.094 P<0.001 ** |P<0.001 ** (e) P=0.007 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.121 P<0.001 ** |P<0.001 ** (e) P=0.003 ** P<0.001 ** | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |10/50 (20%) 8/50 (16%) 11/49 (22%) 11/50 (22%) | |POLY-3 RATE (b) | |10/46.19 8/46.50 11/47.36 11/47.28 | |POLY-3 PERCENT (g) | |21.7% 17.2% 23.2% 23.3% | |TERMINAL (d) | |9/41 (22%) 5/37 (14%) 10/44 (23%) 9/43 (21%) | |FIRST INCIDENCE | |698 575 568 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.444 P=0.477N P=0.569 P=0.544 | |POLY 3 | |P=0.383 P=0.391N P=0.526 P=0.524 | |POLY 1.5 | |P=0.368 P=0.393N P=0.508 P=0.509 | |POLY 6 | |P=0.405 P=0.394N P=0.543 P=0.542 | |LOGISTIC REGRESSION| |P=0.361 P=0.403N P=0.514 P=0.507 | |COCH-ARM / FISHERS | |P=0.358 P=0.398N P=0.479 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 1/50 (2%) 1/49 (2%) 3/50 (6%) | |POLY-3 RATE (b) | |2/46.06 1/45.42 1/46.83 3/47.08 | |POLY-3 PERCENT (g) | |4.3% 2.2% 2.1% 6.4% | |TERMINAL (d) | |2/41 (5%) 1/37 (3%) 1/44 (2%) 2/43 (5%) | |FIRST INCIDENCE | |733 (T) 733 (T) 733 (T) 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.356 P=0.536N P=0.475N P=0.519 | |POLY 3 | |P=0.335 P=0.505N P=0.494N P=0.510 | |POLY 1.5 | |P=0.329 P=0.502N P=0.499N P=0.504 | |POLY 6 | |P=0.344 P=0.510N P=0.490N P=0.518 | |LOGISTIC REGRESSION| |P=0.324 P=0.536N P=0.475N P=0.501 | |COCH-ARM / FISHERS | |P=0.324 P=0.500N P=0.508N P=0.500 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 8/50 (16%) 14/50 (28%) 10/50 (20%) |25/50 (50%) 16/50 (32%) 24/50 (48%) 18/50 (36%) | |POLY-3 RATE (b) | 10/48.41 8/48.13 14/45.01 10/49.55 |25/46.80 16/45.75 24/47.80 18/46.54 | |POLY-3 PERCENT (g) | 20.7% 16.6% 31.1% 20.2% |53.4% 35.0% 50.2% 38.7% | |TERMINAL (d) | 10/47 (21%) 8/46 (17%) 13/39 (33%) 10/49 (20%) |24/41 (59%) 14/37 (38%) 24/44 (55%) 18/43 (42%) | |FIRST INCIDENCE | 728 (T) 728 (T) 702 728 (T) |463 652 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.465 P=0.417N P=0.108 P=0.558N |P=0.108N P=0.103N P=0.359N P=0.069N | |POLY 3 | P=0.457 P=0.403N P=0.179 P=0.576N |P=0.195N P=0.054N P=0.458N P=0.108N | |POLY 1.5 | P=0.455 P=0.401N P=0.208 P=0.578N |P=0.208N P=0.052N P=0.474N P=0.114N | |POLY 6 | P=0.460 P=0.407N P=0.150 P=0.574N |P=0.176N P=0.058N P=0.440N P=0.100N | |LOGISTIC REGRESSION| P=0.452 P=0.417N P=0.118 P=0.558N |P=0.154N P=0.057N P=0.406N P=0.093N | |COCH-ARM / FISHERS | P=0.430 P=0.398N P=0.241 P=0.598N |P=0.212N P=0.052N P=0.500N P=0.113N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/49 (6%) 0/50 (0%) 0/49 (0%) |0/49 (0%) 1/50 (2%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.41 3/47.13 0/44.90 0/48.55 |0/45.09 1/45.42 2/46.80 0/46.54 | |POLY-3 PERCENT (g) | 2.1% 6.4% 0.0% 0.0% |0.0% 2.2% 4.3% 0.0% | |TERMINAL (d) | 1/47 (2%) 3/45 (7%) 0/39 (0%) 0/48 (0%) |0/41 (0%) 1/37 (3%) 2/43 (5%) 0/43 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- --- |--- 733 (T) 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.157N P=0.290 P=0.537N P=0.496N |P=0.593N P=0.480 P=0.249 (e) | |POLY 3 | P=0.154N P=0.296 P=0.515N P=0.499N |P=0.607N P=0.501 P=0.246 (e) | |POLY 1.5 | P=0.152N P=0.297 P=0.508N P=0.500N |P=0.611N P=0.503 P=0.243 (e) | |POLY 6 | P=0.155N P=0.294 P=0.523N P=0.499N |P=0.601N P=0.498 P=0.249 (e) | |LOGISTIC REGRESSION| P=0.157N P=0.290 (e) (e) |(e) P=0.480 P=0.249 (e) | |COCH-ARM / FISHERS | P=0.155N P=0.301 P=0.500N P=0.505N |P=0.612N P=0.505 P=0.247 (e) | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 6/49 (12%) 4/50 (8%) 5/49 (10%) |5/49 (10%) 6/50 (12%) 2/49 (4%) 4/50 (8%) | |POLY-3 RATE (b) | 5/48.41 6/47.13 4/44.90 5/48.55 |5/45.09 6/45.94 2/46.80 4/46.54 | |POLY-3 PERCENT (g) | 10.3% 12.7% 8.9% 10.3% |11.1% 13.1% 4.3% 8.6% | |TERMINAL (d) | 5/47 (11%) 6/45 (13%) 4/39 (10%) 5/48 (10%) |5/41 (12%) 5/37 (14%) 2/43 (5%) 4/43 (9%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) |733 (T) 575 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.488N P=0.470 P=0.616N P=0.617N |P=0.273N P=0.436 P=0.198N P=0.470N | |POLY 3 | P=0.500N P=0.481 P=0.547N P=0.628N |P=0.302N P=0.513 P=0.201N P=0.480N | |POLY 1.5 | P=0.499N P=0.483 P=0.524N P=0.629N |P=0.308N P=0.514 P=0.207N P=0.486N | |POLY 6 | P=0.501N P=0.478 P=0.573N P=0.627N |P=0.294N P=0.507 P=0.196N P=0.473N | |LOGISTIC REGRESSION| P=0.488N P=0.470 P=0.616N P=0.617N |P=0.297N P=0.506 P=0.198N P=0.470N | |COCH-ARM / FISHERS | P=0.510N P=0.486 P=0.500N P=0.617 |P=0.311N P=0.514 P=0.218N P=0.487N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 31/50 (62%) 27/50 (54%) 22/50 (44%) | | |POLY-3 RATE (b) | 29/48.41 31/49.00 27/48.26 22/49.55 | | |POLY-3 PERCENT (g) | 59.9% 63.3% 56.0% 44.4% | | |TERMINAL (d) | 29/47 (62%) 28/46 (61%) 20/39 (51%) 22/49 (45%) | | |FIRST INCIDENCE | 728 (T) 594 498 728 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049N* P=0.374 P=0.367 P=0.075N | | |POLY 3 | P=0.039N* P=0.448 P=0.426N P=0.090N | | |POLY 1.5 | P=0.040N* P=0.434 P=0.412N P=0.093N | | |POLY 6 | P=0.039N* P=0.464 P=0.441N P=0.088N | | |LOGISTIC REGRESSION| P=0.046N* P=0.409 P=0.453N P=0.075N | | |COCH-ARM / FISHERS | P=0.054N P=0.419 P=0.420N P=0.115N | | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland: Duct | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 20/50 (40%) 27/50 (54%) 17/50 (34%) 13/50 (26%) | | |POLY-3 RATE (b) | 20/48.49 27/49.00 17/47.65 13/50.00 | | |POLY-3 PERCENT (g) | 41.3% 55.1% 35.7% 26.0% | | |TERMINAL (d) | 19/47 (40%) 24/46 (52%) 11/39 (28%) 12/49 (25%) | | |FIRST INCIDENCE | 708 594 498 596 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.023N* P=0.108 P=0.567 P=0.083N | | |POLY 3 | P=0.014N* P=0.122 P=0.363N P=0.082N | | |POLY 1.5 | P=0.014N* P=0.117 P=0.346N P=0.085N | | |POLY 6 | P=0.013N* P=0.127 P=0.383N P=0.079N | | |LOGISTIC REGRESSION| P=0.020N* P=0.110 P=0.342N P=0.091N | | |COCH-ARM / FISHERS | P=0.021N* P=0.115 P=0.339N P=0.101N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/49 (2%) 0/50 (0%) |0/50 (0%) 0/48 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/48.49 0/48.13 1/44.51 0/49.55 |0/46.06 0/44.01 0/47.61 1/47.08 | |POLY-3 PERCENT (g) | 6.2% 0.0% 2.3% 0.0% |0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 2/47 (4%) 0/46 (0%) 1/39 (3%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 708 --- 728 (T) --- |--- --- --- 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.091N P=0.128N P=0.377N P=0.117N |P=0.201 (e) (e) P=0.504 | |POLY 3 | P=0.085N P=0.120N P=0.337N P=0.115N |P=0.205 (e) (e) P=0.504 | |POLY 1.5 | P=0.085N P=0.120N P=0.325N P=0.116N |P=0.203 (e) (e) P=0.502 | |POLY 6 | P=0.084N P=0.122N P=0.351N P=0.115N |P=0.208 (e) (e) P=0.508 | |LOGISTIC REGRESSION| P=0.087N P=0.121N P=0.343N P=0.118N |P=0.255 (e) (e) P=0.560 | |COCH-ARM / FISHERS | P=0.087N P=0.121N P=0.316N P=0.121N |P=0.201 (e) (e) P=0.500 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 31/50 (62%) 33/50 (66%) 26/49 (53%) 29/50 (58%) |32/50 (64%) 27/48 (56%) 27/49 (55%) 27/50 (54%) | |POLY-3 RATE (b) | 31/48.41 33/48.44 26/44.62 29/49.55 |32/47.52 27/45.60 27/47.77 27/47.28 | |POLY-3 PERCENT (g) | 64.0% 68.1% 58.3% 58.5% |67.3% 59.2% 56.5% 57.1% | |TERMINAL (d) | 31/47 (66%) 32/46 (70%) 25/39 (64%) 29/49 (59%) |28/41 (68%) 22/37 (60%) 26/44 (59%) 25/43 (58%) | |FIRST INCIDENCE | 728 (T) 644 702 728 (T) |463 558 691 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.203N P=0.359 P=0.561 P=0.318N |P=0.111N P=0.405N P=0.115N P=0.148N | |POLY 3 | P=0.233N P=0.417 P=0.359N P=0.363N |P=0.200N P=0.272N P=0.188N P=0.205N | |POLY 1.5 | P=0.234N P=0.415 P=0.296N P=0.369N |P=0.211N P=0.277N P=0.206N P=0.215N | |POLY 6 | P=0.234N P=0.415 P=0.441N P=0.358N |P=0.183N P=0.273N P=0.175N P=0.190N | |LOGISTIC REGRESSION| P=0.228N P=0.384 P=0.588N P=0.318N |P=0.180N P=0.280N P=0.154N P=0.193N | |COCH-ARM / FISHERS | P=0.276N P=0.418 P=0.243N P=0.419N |P=0.206N P=0.282N P=0.243N P=0.208N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) |0/50 (0%) 0/48 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 2/44.99 0/49.55 |0/46.06 0/44.01 0/47.61 1/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 0.0% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 1/39 (3%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 1/43 (2%) | |FIRST INCIDENCE | --- --- 588 --- |--- --- --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.598 (e) P=0.210 (e) |P=0.210 (e) (e) P=0.510 | |POLY 3 | P=0.612 (e) P=0.221 (e) |P=0.203 (e) (e) P=0.502 | |POLY 1.5 | P=0.609 (e) P=0.227 (e) |P=0.202 (e) (e) P=0.500 | |POLY 6 | P=0.616 (e) P=0.215 (e) |P=0.206 (e) (e) P=0.504 | |LOGISTIC REGRESSION| P=0.567 (e) P=0.232 (e) |(e) (e) (e) P=0.510 | |COCH-ARM / FISHERS | P=0.594 (e) P=0.242 (e) |P=0.201 (e) (e) P=0.500 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Skin: Subcutaneous Tissue | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.41 1/48.24 2/45.73 0/49.55 |0/46.06 0/45.42 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 2.1% 4.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | --- 701 561 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.610N P=0.496 P=0.221 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.606N P=0.499 P=0.225 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.607N P=0.500 P=0.231 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.605N P=0.499 P=0.218 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.651 P=0.501 P=0.222 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.616N P=0.500 P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 10/50 (20%) 8/49 (16%) 5/50 (10%) |16/49 (33%) 15/50 (30%) 9/50 (18%) 11/50 (22%) | |POLY-3 RATE (b) | 8/48.92 10/48.89 8/46.45 5/49.55 |16/47.49 15/47.80 9/48.13 11/48.91 | |POLY-3 PERCENT (g) | 16.4% 20.5% 17.2% 10.1% |33.7% 31.4% 18.7% 22.5% | |TERMINAL (d) | 7/47 (15%) 8/46 (17%) 4/39 (10%) 5/49 (10%) |10/41 (24%) 9/37 (24%) 8/44 (18%) 8/43 (19%) | |FIRST INCIDENCE | 572 594 365 728 (T) |463 325 642 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.167N P=0.386 P=0.478 P=0.254N |P=0.090N P=0.568 P=0.071N P=0.179N | |POLY 3 | P=0.165N P=0.397 P=0.563 P=0.269N |P=0.091N P=0.491N P=0.074N P=0.159N | |POLY 1.5 | P=0.163N P=0.397 P=0.581 P=0.268N |P=0.094N P=0.479N P=0.073N P=0.161N | |POLY 6 | P=0.168N P=0.397 P=0.540 P=0.271N |P=0.091N P=0.516N P=0.078N P=0.164N | |LOGISTIC REGRESSION| P=0.192N P=0.398 P=0.594N P=0.280N |P=0.101N P=0.459N P=0.090N P=0.167N | |COCH-ARM / FISHERS | P=0.171N P=0.398 P=0.590 P=0.277N |P=0.099N P=0.473N P=0.074N P=0.168N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/49 (2%) 1/50 (2%) |0/49 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.49 1/49.13 1/44.99 1/50.00 |0/45.09 2/45.98 2/48.36 0/46.54 | |POLY-3 PERCENT (g) | 2.1% 2.0% 2.2% 2.0% |0.0% 4.4% 4.1% 0.0% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | 708 50 588 596 |--- 596 568 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.625N P=0.756 P=0.727 P=0.753N |P=0.484N P=0.234 P=0.255 (e) | |POLY 3 | P=0.629N P=0.757N P=0.744 P=0.753N |P=0.489N P=0.242 P=0.253 (e) | |POLY 1.5 | P=0.630N P=0.757N P=0.750 P=0.755N |P=0.493N P=0.242 P=0.249 (e) | |POLY 6 | P=0.628N P=0.759N P=0.736 P=0.752N |P=0.483N P=0.240 P=0.258 (e) | |LOGISTIC REGRESSION| P=0.417 P=0.775N P=0.759 P=0.724 |P=0.468N P=0.248 P=0.195 (e) | |COCH-ARM / FISHERS | P=0.633 P=0.753N P=0.747 P=0.753N |P=0.495N P=0.253 P=0.253 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |4/49 (8%) 1/50 (2%) 0/50 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/44.51 0/49.55 |4/45.09 1/45.42 0/47.80 4/47.40 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |8.9% 2.2% 0.0% 8.4% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |4/41 (10%) 1/37 (3%) 0/44 (0%) 3/43 (7%) | |FIRST INCIDENCE | --- --- --- --- |733 (T) 733 (T) --- 379 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.513 P=0.211N P=0.055N P=0.621N | |POLY 3 | (e) (e) (e) (e) |P=0.497 P=0.176N P=0.053N P=0.615N | |POLY 1.5 | (e) (e) (e) (e) |P=0.491 P=0.175N P=0.055N P=0.623N | |POLY 6 | (e) (e) (e) (e) |P=0.505 P=0.181N P=0.052N P=0.607N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.486 P=0.211N (e) P=0.629N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.484 P=0.175N P=0.056N P=0.631N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/48 (6%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.41 2/49.24 3/45.17 0/49.55 |1/46.82 1/45.44 2/48.30 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 4.1% 6.6% 0.0% |2.1% 2.2% 4.1% 0.0% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | --- 50 533 --- |456 728 638 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.525N P=0.237 P=0.113 (e) |P=0.360N P=0.750 P=0.513 P=0.508N | |POLY 3 | P=0.519N P=0.241 P=0.107 (e) |P=0.365N P=0.754 P=0.511 P=0.501N | |POLY 1.5 | P=0.521N P=0.241 P=0.110 (e) |P=0.368N P=0.757 P=0.506 P=0.502N | |POLY 6 | P=0.518N P=0.241 P=0.104 (e) |P=0.361N P=0.750 P=0.517 P=0.500N | |LOGISTIC REGRESSION| P=0.490 P=0.224 P=0.084 (e) |P=0.324N P=0.747N P=0.375 P=0.344N | |COCH-ARM / FISHERS | P=0.532N P=0.247 P=0.114 (e) |P=0.366N P=0.753N P=0.500 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/48 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/43.55 0/49.55 |0/46.06 0/45.42 0/47.80 2/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.3% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 0/49 (0%) |0/41 (0%) 0/37 (0%) 0/44 (0%) 2/43 (5%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.053 (e) (e) P=0.249 | |POLY 3 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.240 | |POLY 1.5 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.238 | |POLY 6 | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.242 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.249 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 1/50 (2%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 0/48.41 0/48.13 0/44.90 1/49.55 |2/46.06 1/45.42 1/47.80 3/46.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.0% |4.3% 2.2% 2.1% 6.5% | |TERMINAL (d) | 0/47 (0%) 0/46 (0%) 0/39 (0%) 1/49 (2%) |2/41 (5%) 1/37 (3%) 1/44 (2%) 3/43 (7%) | |FIRST INCIDENCE | --- --- --- 728 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.209 (e) (e) P=0.508 |P=0.359 P=0.536N P=0.475N P=0.522 | |POLY 3 | P=0.202 (e) (e) P=0.505 |P=0.332 P=0.505N P=0.487N P=0.505 | |POLY 1.5 | P=0.202 (e) (e) P=0.504 |P=0.328 P=0.502N P=0.492N P=0.501 | |POLY 6 | P=0.203 (e) (e) P=0.505 |P=0.339 P=0.510N P=0.482N P=0.510 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.508 |P=0.359 P=0.536N P=0.475N P=0.522 | |COCH-ARM / FISHERS | P=0.198 (e) (e) P=0.500 |P=0.324 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Testes | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 3/50 (6%) 1/50 (2%) | | |POLY-3 RATE (b) | 0/48.41 3/48.13 3/44.90 1/49.55 | | |POLY-3 PERCENT (g) | 0.0% 6.2% 6.7% 2.0% | | |TERMINAL (d) | 0/47 (0%) 3/46 (7%) 3/39 (8%) 1/49 (2%) | | |FIRST INCIDENCE | --- 728 (T) 728 (T) 728 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.538 P=0.118 P=0.091 P=0.508 | | |POLY 3 | P=0.543 P=0.118 P=0.106 P=0.505 | | |POLY 1.5 | P=0.541 P=0.118 P=0.112 P=0.504 | | |POLY 6 | P=0.544 P=0.117 P=0.099 P=0.505 | | |LOGISTIC REGRESSION| (e) P=0.118 P=0.091 P=0.508 | | |COCH-ARM / FISHERS | P=0.526 P=0.121 P=0.121 P=0.500 | | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/43 (5%) 3/44 (7%) 3/44 (7%) 1/49 (2%) |2/47 (4%) 3/46 (7%) 2/47 (4%) 1/47 (2%) | |POLY-3 RATE (b) | 2/41.92 3/44.00 3/42.53 1/48.55 |2/44.05 3/42.28 2/45.16 1/43.74 | |POLY-3 PERCENT (g) | 4.8% 6.8% 7.1% 2.1% |4.5% 7.1% 4.4% 2.3% | |TERMINAL (d) | 2/41 (5%) 0/41 (0%) 0/37 (0%) 1/48 (2%) |0/39 (0%) 1/35 (3%) 0/41 (0%) 1/41 (2%) | |FIRST INCIDENCE | 728 (T) 50 498 728 (T) |609 668 642 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.323N P=0.500 P=0.470 P=0.445N |P=0.296N P=0.471 P=0.672N P=0.492N | |POLY 3 | P=0.289N P=0.522 P=0.507 P=0.449N |P=0.311N P=0.481 P=0.685N P=0.502N | |POLY 1.5 | P=0.288N P=0.521 P=0.512 P=0.448N |P=0.313N P=0.485 P=0.688N P=0.503N | |POLY 6 | P=0.291N P=0.523 P=0.499 P=0.450N |P=0.309N P=0.474 P=0.683N P=0.502N | |LOGISTIC REGRESSION| P=0.474N P=0.530 P=0.466 P=0.445N |P=0.303N P=0.501 P=0.655 P=0.491N | |COCH-ARM / FISHERS | P=0.292N P=0.511 P=0.511 P=0.451N |P=0.310N P=0.490 P=0.692N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/47.49 1/48.13 1/44.90 0/49.55 |2/46.19 0/44.99 0/47.80 0/46.54 | |POLY-3 PERCENT (g) | 0.0% 2.1% 2.2% 0.0% |4.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/47 (0%) 1/46 (2%) 1/39 (3%) 0/49 (0%) |1/41 (2%) 0/37 (0%) 0/44 (0%) 0/43 (0%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) --- |698 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.585N P=0.496 P=0.463 (e) |P=0.110N P=0.259N P=0.227N P=0.232N | |POLY 3 | P=0.587N P=0.503 P=0.489 (e) |P=0.112N P=0.243N P=0.230N P=0.236N | |POLY 1.5 | P=0.586N P=0.503 P=0.496 (e) |P=0.112N P=0.242N P=0.233N P=0.237N | |POLY 6 | P=0.587N P=0.501 P=0.480 (e) |P=0.111N P=0.246N P=0.227N P=0.234N | |LOGISTIC REGRESSION| (e) P=0.496 P=0.463 (e) |P=0.114N P=0.242N P=0.235N P=0.237N | |COCH-ARM / FISHERS | P=0.592N P=0.505 P=0.505 (e) |P=0.115N P=0.253N P=0.247N P=0.247N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 4/50 (8%) 5/50 (10%) 5/50 (10%) |3/50 (6%) 4/49 (8%) 10/50 (20%) 4/50 (8%) | |POLY-3 RATE (b) | 4/47.49 4/48.13 5/45.01 5/49.55 |3/46.06 4/44.99 10/47.80 4/46.54 | |POLY-3 PERCENT (g) | 8.4% 8.3% 11.1% 10.1% |6.5% 8.9% 20.9% 8.6% | |TERMINAL (d) | 4/47 (9%) 4/46 (9%) 4/39 (10%) 5/49 (10%) |3/41 (7%) 4/37 (11%) 10/44 (23%) 4/43 (9%) | |FIRST INCIDENCE | 728 (T) 728 (T) 702 728 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.425 P=0.632 P=0.387 P=0.526 |P=0.426 P=0.444 P=0.048 * P=0.526 | |POLY 3 | P=0.426 P=0.635N P=0.467 P=0.526 |P=0.378 P=0.487 P=0.041 * P=0.506 | |POLY 1.5 | P=0.426 P=0.634N P=0.489 P=0.525 |P=0.368 P=0.489 P=0.039 * P=0.501 | |POLY 6 | P=0.426 P=0.639N P=0.441 P=0.527 |P=0.392 P=0.482 P=0.043 * P=0.512 | |LOGISTIC REGRESSION| P=0.422 P=0.632 P=0.427 P=0.526 |P=0.426 P=0.444 P=0.048 * P=0.526 | |COCH-ARM / FISHERS | P=0.411 P=0.631N P=0.513 P=0.513 |P=0.368 P=0.489 P=0.036 * P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Tooth | | Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 0/0 (0%) 1/1 (100%) 2/2 (100%) |1/2 (50%) 0/0 (0%) 1/1 (100%) 1/1 (100%) | |POLY-3 RATE (b) | 1/1.00 0/0.00 1/1.00 2/2.00 |1/2.00 0/0.00 1/1.00 1/1.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 100.0% 100.0% |50.0% 0.0% 100.0% 100.0% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 0/0 (0%) 2/2 (100%) |1/2 (50%) 0/0 (0%) 1/1 (100%) 1/1 (100%) | |FIRST INCIDENCE | 728 (T) --- 365 728 (T) |733 (T) --- 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.382 P=1.000 P=0.638 P=0.638 | |POLY 3 | (e) (e) (e) (e) |(e) (e) P=0.614 P=0.614 | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) P=0.614 P=0.614 | |POLY 6 | (e) (e) (e) (e) |(e) (e) P=0.614 P=0.614 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.382 (e) P=0.638 P=0.638 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.364 P=1.000 P=0.667 P=0.667 | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 36 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/50 (32%) 20/50 (40%) 18/50 (36%) 21/50 (42%) |33/50 (66%) 39/50 (78%) 33/50 (66%) 33/50 (66%) | |POLY-3 RATE (b) | 16/48.41 20/48.13 18/46.06 21/50.00 |33/47.37 39/47.39 33/48.83 33/47.65 | |POLY-3 PERCENT (g) | 33.1% 41.6% 39.1% 42.0% |69.7% 82.3% 67.6% 69.3% | |TERMINAL (d) | 16/47 (34%) 20/46 (44%) 16/39 (41%) 20/49 (41%) |30/41 (73%) 32/37 (87%) 30/44 (68%) 30/43 (70%) | |FIRST INCIDENCE | 728 (T) 728 (T) 365 596 |463 551 568 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.268 P=0.237 P=0.196 P=0.254 |P=0.167N P=0.041 * P=0.400N P=0.461N | |POLY 3 | P=0.260 P=0.258 P=0.347 P=0.241 |P=0.319N P=0.107 P=0.500N P=0.571N | |POLY 1.5 | P=0.255 P=0.261 P=0.385 P=0.234 |P=0.351N P=0.114 P=0.535N P=0.581 | |POLY 6 | P=0.268 P=0.251 P=0.301 P=0.249 |P=0.272N P=0.099 P=0.461N P=0.534N | |LOGISTIC REGRESSION| P=0.243 P=0.237 P=0.355 P=0.223 |P=0.319N P=0.111 P=0.504N P=0.571N | |COCH-ARM / FISHERS | P=0.222 P=0.266 P=0.417 P=0.204 |P=0.358N P=0.133 P=0.583N P=0.583N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |7/50 (14%) 3/50 (6%) 2/50 (4%) 6/50 (12%) | |POLY-3 RATE (b) | |7/46.47 3/45.64 2/47.80 6/46.54 | |POLY-3 PERCENT (g) | |15.1% 6.6% 4.2% 12.9% | |TERMINAL (d) | |6/41 (15%) 2/37 (5%) 2/44 (5%) 6/43 (14%) | |FIRST INCIDENCE | |614 673 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.477N P=0.201N P=0.067N P=0.465N | |POLY 3 | |P=0.524N P=0.165N P=0.072N P=0.499N | |POLY 1.5 | |P=0.530N P=0.162N P=0.075N P=0.503N | |POLY 6 | |P=0.516N P=0.171N P=0.071N P=0.494N | |LOGISTIC REGRESSION| |P=0.520N P=0.162N P=0.075N P=0.491N | |COCH-ARM / FISHERS | |P=0.533N P=0.159N P=0.080N P=0.500N | |=================================================================================================================================| Date: 06/14/01 EXPERIMENT: 56111 TEST: 04 Page 37 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |42/50 (84%) 46/50 (92%) 41/50 (82%) 48/50 (96%) | |POLY-3 RATE (b) | |42/48.12 46/48.70 41/48.36 48/49.80 | |POLY-3 PERCENT (g) | |87.3% 94.5% 84.8% 96.4% | |TERMINAL (d) | |38/41 (93%) 37/37 (100%) 39/44 (89%) 42/43 (98%) | |FIRST INCIDENCE | |463 325 568 226 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.446 P=0.040 * P=0.220N P=0.206 | |POLY 3 | |P=0.133 P=0.171 P=0.474N P=0.086 | |POLY 1.5 | |P=0.107 P=0.176 P=0.486N P=0.065 | |POLY 6 | |P=0.175 P=0.160 P=0.461N P=0.117 | |LOGISTIC REGRESSION| |P=0.073 P=0.160 P=0.357N P=0.041 * | |COCH-ARM / FISHERS | |P=0.083 P=0.178 P=0.500N P=0.046 * | |=================================================================================================================================| (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).