TDMS Study 56111-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANS-CINNAMALDEHYDE DATE: 06/29/01 EXPERIMENT: 56111 TEST: 03 TIME: 08:39:18 TEST TYPE: CHRONIC PAGE: 1 CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: 56111B PATHOLOGIST: TOFT, JOHN CAS: 14371-10-9 ------------------------------------------------------------------------------------------------------------------------------------ Final#1/Rats 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: 06/29/01 EXPERIMENT: 56111 TEST: 03 TIME: 08:39:18 TEST TYPE: CHRONIC CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: 56111B PATHOLOGIST: TOFT, JOHN CAS: 14371-10-9 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANS-CINNAMALDEHYDE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Hyperplasia Bone Marrow Hyperplasia Eye: Retina Degeneration Heart Cardiomyopathy Kidney Nephropathy Liver Inflammation Chronic Liver: Bile Duct Hyperplasia Liver: Hepatocyte Vacuolization Cytoplasmic Lung Fibrosis Pigmentation Lung: Alveolus Infiltration Cellular Histiocyte Mammary Gland Hyperplasia Cystic Mesentery: Fat Necrosis Pancreas: Acinus Atrophy Pancreas: Duct Cyst Preputial Gland Inflammation Chronic Prostate Inflammation Chronic Salivary Glands Atrophy Basophilic Focus =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Brain Hemorrhage Clitoral Gland Inflammation Chronic Clitoral Gland: Duct Cyst Intestine Large, Colon Parasite Metazoan Kidney Mineralization Liver Hepatodiaphragmatic Nodule Liver: Bile Duct Hyperplasia Liver: Hepatocyte Vacuolization Cytoplasmic Mammary Gland Hyperplasia Cystic Oral Mucosa Foreign Body Oral Mucosa: Gingival Inflammation Chronic Pancreas: Acinus Atrophy Pancreas: Duct Cyst Salivary Glands Atrophy Thyroid Gland: C-Cell Hyperplasia =============================================================== Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 2/50 (4%) |2/50 (4%) 1/50 (2%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/41.64 2/45.17 1/39.67 2/47.85 |2/45.91 1/44.73 0/42.98 1/44.31 | |POLY-3 PERCENT (g) | 0.0% 4.4% 2.5% 4.2% |4.4% 2.2% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 2/36 (6%) 1/27 (4%) 2/41 (5%) |2/36 (6%) 1/33 (3%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 731 (T) 731 (T) 731 (T) |735 (T) 735 (T) --- 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.320 P=0.272 P=0.472 P=0.302 |P=0.382N P=0.530N P=0.244N P=0.523N | |POLY 3 | P=0.295 P=0.256 P=0.490 P=0.270 |P=0.372N P=0.509N P=0.252N P=0.512N | |POLY 1.5 | P=0.274 P=0.246 P=0.492 P=0.256 |P=0.371N P=0.507N P=0.250N P=0.509N | |POLY 6 | P=0.323 P=0.268 P=0.487 P=0.287 |P=0.371N P=0.513N P=0.252N P=0.516N | |LOGISTIC REGRESSION| (e) P=0.272 P=0.472 P=0.302 |P=0.380N P=0.530N (e) P=0.516N | |COCH-ARM / FISHERS | P=0.246 P=0.247 P=0.500 P=0.247 |P=0.367N P=0.500N P=0.253N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 2/50 (4%) 7/50 (14%) |1/50 (2%) 5/50 (10%) 2/49 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 2/41.64 5/45.17 2/39.67 7/48.07 |1/45.91 5/45.24 2/42.98 1/44.16 | |POLY-3 PERCENT (g) | 4.8% 11.1% 5.0% 14.6% |2.2% 11.1% 4.7% 2.3% | |TERMINAL (d) | 2/31 (7%) 5/36 (14%) 2/27 (7%) 6/41 (15%) |1/36 (3%) 3/33 (9%) 2/35 (6%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 672 |735 (T) 652 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.158 P=0.278 P=0.645 P=0.169 |P=0.372N P=0.091 P=0.490 P=0.742 | |POLY 3 | P=0.109 P=0.250 P=0.677 P=0.119 |P=0.366N P=0.098 P=0.477 P=0.752 | |POLY 1.5 | P=0.094 P=0.233 P=0.680 P=0.101 |P=0.360N P=0.098 P=0.480 P=0.754 | |POLY 6 | P=0.130 P=0.272 P=0.671 P=0.144 |P=0.372N P=0.097 P=0.476 P=0.749 | |LOGISTIC REGRESSION| P=0.152 P=0.278 P=0.645 P=0.151 |P=0.361N P=0.099 P=0.490 P=0.742 | |COCH-ARM / FISHERS | P=0.079 P=0.218 P=0.691N P=0.080 |P=0.344N P=0.102 P=0.492 P=0.753N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 16/50 (32%) 14/50 (28%) 13/50 (26%) |17/50 (34%) 9/50 (18%) 12/49 (24%) 10/50 (20%) | |POLY-3 RATE (b) | 9/42.63 16/45.17 14/40.43 13/47.85 |17/46.54 9/44.73 12/44.17 10/45.36 | |POLY-3 PERCENT (g) | 21.1% 35.4% 34.6% 27.2% |36.5% 20.1% 27.2% 22.0% | |TERMINAL (d) | 6/31 (19%) 16/36 (44%) 11/27 (41%) 13/41 (32%) |14/36 (39%) 9/33 (27%) 9/35 (26%) 6/33 (18%) | |FIRST INCIDENCE | 577 731 (T) 627 731 (T) |652 735 (T) 498 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.472N P=0.160 P=0.103 P=0.489 |P=0.179N P=0.084N P=0.229N P=0.144N | |POLY 3 | P=0.472 P=0.103 P=0.125 P=0.336 |P=0.134N P=0.063N P=0.232N P=0.095N | |POLY 1.5 | P=0.411 P=0.090 P=0.137 P=0.292 |P=0.136N P=0.061N P=0.229N P=0.095N | |POLY 6 | P=0.548 P=0.120 P=0.111 P=0.392 |P=0.128N P=0.070N P=0.227N P=0.095N | |LOGISTIC REGRESSION| P=0.521N P=0.153 P=0.125 P=0.401 |P=0.155N P=0.069N P=0.243N P=0.104N | |COCH-ARM / FISHERS | P=0.332 P=0.083 P=0.171 P=0.235 |P=0.133N P=0.055N P=0.207N P=0.088N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 1/50 (2%) 2/50 (4%) |4/50 (8%) 2/50 (4%) 3/49 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 3/42.09 2/45.17 1/39.67 2/47.85 |4/45.91 2/45.20 3/42.98 2/44.16 | |POLY-3 PERCENT (g) | 7.1% 4.4% 2.5% 4.2% |8.7% 4.4% 7.0% 4.5% | |TERMINAL (d) | 2/31 (7%) 2/36 (6%) 1/27 (4%) 2/41 (5%) |4/36 (11%) 1/33 (3%) 3/35 (9%) 2/33 (6%) | |FIRST INCIDENCE | 598 731 (T) 731 (T) 731 (T) |735 (T) 597 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.321N P=0.438N P=0.348N P=0.386N |P=0.347N P=0.371N P=0.516N P=0.377N | |POLY 3 | P=0.380N P=0.468N P=0.326N P=0.442N |P=0.336N P=0.344N P=0.536N P=0.355N | |POLY 1.5 | P=0.391N P=0.484N P=0.321N P=0.466N |P=0.331N P=0.345N P=0.530N P=0.350N | |POLY 6 | P=0.367N P=0.448N P=0.335N P=0.413N |P=0.340N P=0.346N P=0.537N P=0.361N | |LOGISTIC REGRESSION| P=0.349N P=0.474N P=0.321N P=0.475N |P=0.340N P=0.344N P=0.516N P=0.377N | |COCH-ARM / FISHERS | P=0.404N P=0.500N P=0.309N P=0.500N |P=0.320N P=0.339N P=0.511N P=0.339N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 3/50 (6%) 1/50 (2%) |1/50 (2%) 2/50 (4%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 2/42.04 0/45.17 3/40.47 1/48.20 |1/46.16 2/45.69 1/43.40 1/44.70 | |POLY-3 PERCENT (g) | 4.8% 0.0% 7.4% 2.1% |2.2% 4.4% 2.3% 2.2% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 1/27 (4%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 647 --- 609 633 |670 561 613 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.476N P=0.203N P=0.468 P=0.405N |P=0.550N P=0.497 P=0.737 P=0.747 | |POLY 3 | P=0.518N P=0.221N P=0.483 P=0.453N |P=0.542N P=0.497 P=0.747 P=0.754 | |POLY 1.5 | P=0.532N P=0.229N P=0.485 P=0.472N |P=0.539N P=0.496 P=0.749 P=0.755 | |POLY 6 | P=0.501N P=0.212N P=0.477 P=0.429N |P=0.545N P=0.496 P=0.747 P=0.751 | |LOGISTIC REGRESSION| P=0.589N P=0.241N P=0.504 P=0.621N |P=0.484N P=0.588 P=0.729N P=0.708N | |COCH-ARM / FISHERS | P=0.556N P=0.247N P=0.500 P=0.500N |P=0.531N P=0.500 P=0.747 P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 27/50 (54%) 30/50 (60%) 33/50 (66%) 24/50 (48%) |18/50 (36%) 25/50 (50%) 19/49 (39%) 20/50 (40%) | |POLY-3 RATE (b) | 27/47.35 30/49.35 33/46.21 24/49.69 |18/46.75 25/46.90 19/44.46 20/45.57 | |POLY-3 PERCENT (g) | 57.0% 60.8% 71.4% 48.3% |38.5% 53.3% 42.7% 43.9% | |TERMINAL (d) | 13/31 (42%) 19/36 (53%) 16/27 (59%) 17/41 (42%) |13/36 (36%) 18/33 (55%) 14/35 (40%) 14/33 (42%) | |FIRST INCIDENCE | 499 170 488 499 |679 597 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.079N P=0.500N P=0.127 P=0.089N |P=0.457 P=0.079 P=0.451 P=0.319 | |POLY 3 | P=0.186N P=0.433 P=0.103 P=0.255N |P=0.499 P=0.106 P=0.421 P=0.376 | |POLY 1.5 | P=0.216N P=0.400 P=0.107 P=0.288N |P=0.514 P=0.103 P=0.430 P=0.386 | |POLY 6 | P=0.157N P=0.463 P=0.101 P=0.224N |P=0.483 P=0.107 P=0.420 P=0.364 | |LOGISTIC REGRESSION| P=0.329N P=0.238 P=0.150 P=0.582N |P=0.504 P=0.094 P=0.407 P=0.356 | |COCH-ARM / FISHERS | P=0.265N P=0.343 P=0.154 P=0.345N |P=0.523N P=0.113 P=0.469 P=0.418 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 14/50 (28%) 8/50 (16%) 5/50 (10%) |6/50 (12%) 3/50 (6%) 3/49 (6%) 3/50 (6%) | |POLY-3 RATE (b) | 9/42.82 14/46.41 8/39.85 5/47.85 |6/45.91 3/44.88 3/43.11 3/44.31 | |POLY-3 PERCENT (g) | 21.0% 30.2% 20.1% 10.5% |13.1% 6.7% 7.0% 6.8% | |TERMINAL (d) | 7/31 (23%) 10/36 (28%) 7/27 (26%) 5/41 (12%) |6/36 (17%) 2/33 (6%) 2/35 (6%) 2/33 (6%) | |FIRST INCIDENCE | 505 591 682 731 (T) |735 (T) 697 702 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.025N* P=0.296 P=0.601 P=0.086N |P=0.246N P=0.282N P=0.255N P=0.283N | |POLY 3 | P=0.037N* P=0.228 P=0.566N P=0.135N |P=0.233N P=0.253N P=0.274N P=0.259N | |POLY 1.5 | P=0.048N* P=0.196 P=0.547N P=0.158N |P=0.230N P=0.252N P=0.270N P=0.255N | |POLY 6 | P=0.026N* P=0.275 P=0.592N P=0.110N |P=0.234N P=0.256N P=0.272N P=0.263N | |LOGISTIC REGRESSION| P=0.040N* P=0.192 P=0.551N P=0.158N |P=0.243N P=0.273N P=0.266N P=0.273N | |COCH-ARM / FISHERS | P=0.068N P=0.171 P=0.500N P=0.194N |P=0.222N P=0.243N P=0.254N P=0.243N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 33/50 (66%) 21/50 (42%) 26/50 (52%) 22/50 (44%) |16/50 (32%) 13/50 (26%) 11/49 (22%) 13/50 (26%) | |POLY-3 RATE (b) | 33/49.34 21/47.29 26/45.94 22/49.51 |16/48.78 13/47.81 11/46.30 13/47.06 | |POLY-3 PERCENT (g) | 66.9% 44.4% 56.6% 44.4% |32.8% 27.2% 23.8% 27.6% | |TERMINAL (d) | 16/31 (52%) 12/36 (33%) 10/27 (37%) 16/41 (39%) |6/36 (17%) 3/33 (9%) 3/35 (9%) 3/33 (9%) | |FIRST INCIDENCE | 429 593 506 499 |523 561 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020N* P=0.011N* P=0.307N P=0.005N** |P=0.387N P=0.410N P=0.264N P=0.422N | |POLY 3 | P=0.043N* P=0.019N* P=0.204N P=0.018N* |P=0.340N P=0.353N P=0.227N P=0.372N | |POLY 1.5 | P=0.046N* P=0.018N* P=0.180N P=0.019N* |P=0.331N P=0.352N P=0.222N P=0.362N | |POLY 6 | P=0.041N* P=0.020N* P=0.226N P=0.017N* |P=0.347N P=0.354N P=0.229N P=0.380N | |LOGISTIC REGRESSION| P=0.082N P=0.020N* P=0.091N P=0.168N |P=0.236N P=0.268N P=0.105N P=0.244N | |COCH-ARM / FISHERS | P=0.057N P=0.013N* P=0.111N P=0.022N* |P=0.306N P=0.330N P=0.200N P=0.330N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone Marrow | | Myelofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 0/49 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 0/41.64 0/45.17 0/39.67 0/47.85 |2/46.09 2/44.80 0/42.98 4/45.40 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.3% 4.5% 0.0% 8.8% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |1/36 (3%) 1/33 (3%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | --- --- --- --- |690 718 --- 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.224 P=0.665 P=0.251N P=0.319 | |POLY 3 | (e) (e) (e) (e) |P=0.227 P=0.684 P=0.253N P=0.330 | |POLY 1.5 | (e) (e) (e) (e) |P=0.228 P=0.686 P=0.250N P=0.331 | |POLY 6 | (e) (e) (e) (e) |P=0.228 P=0.679 P=0.254N P=0.330 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.241 P=0.685 P=0.248N P=0.391 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.232 P=0.691N P=0.253N P=0.339 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Brain | | Compression | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 3/50 (6%) 1/50 (2%) |3/50 (6%) 3/50 (6%) 2/49 (4%) 5/50 (10%) | |POLY-3 RATE (b) | 2/41.64 2/45.64 3/40.76 1/48.01 |3/46.28 3/45.18 2/43.41 5/45.83 | |POLY-3 PERCENT (g) | 4.8% 4.4% 7.4% 2.1% |6.5% 6.6% 4.6% 10.9% | |TERMINAL (d) | 2/31 (7%) 1/36 (3%) 0/27 (0%) 0/41 (0%) |2/36 (6%) 1/33 (3%) 1/35 (3%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) 591 488 691 |632 626 610 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.331N P=0.640N P=0.459 P=0.400N |P=0.246 P=0.630 P=0.522N P=0.329 | |POLY 3 | P=0.351N P=0.661N P=0.490 P=0.451N |P=0.261 P=0.651 P=0.529N P=0.351 | |POLY 1.5 | P=0.372N P=0.677N P=0.489 P=0.471N |P=0.260 P=0.653 P=0.525N P=0.350 | |POLY 6 | P=0.325N P=0.639N P=0.490 P=0.425N |P=0.264 P=0.648 P=0.530N P=0.353 | |LOGISTIC REGRESSION| P=0.431N P=0.688N P=0.506 P=0.435N |P=0.284 P=0.656N P=0.492N P=0.431 | |COCH-ARM / FISHERS | P=0.404N P=0.691N P=0.500 P=0.500N |P=0.264 P=0.661N P=0.510N P=0.357 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Brain | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 1/42.30 4/46.37 2/41.06 1/47.92 |0/45.91 0/44.73 2/44.27 3/44.52 | |POLY-3 PERCENT (g) | 2.4% 8.6% 4.9% 2.1% |0.0% 0.0% 4.5% 6.7% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 508 619 178 715 |--- --- 177 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.340N P=0.242 P=0.498 P=0.726N |P=0.027 * (e) P=0.227 P=0.113 | |POLY 3 | P=0.345N P=0.208 P=0.490 P=0.732N |P=0.026 * (e) P=0.229 P=0.113 | |POLY 1.5 | P=0.370N P=0.193 P=0.492 P=0.744N |P=0.026 * (e) P=0.230 P=0.115 | |POLY 6 | P=0.315N P=0.229 P=0.485 P=0.716N |P=0.026 * (e) P=0.230 P=0.112 | |LOGISTIC REGRESSION| P=0.500N P=0.170 P=0.752N P=0.596 |P=0.031 * (e) P=0.550 P=0.119 | |COCH-ARM / FISHERS | P=0.403N P=0.181 P=0.500 P=0.753N |P=0.028 * (e) P=0.242 P=0.121 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 5/50 (10%) 2/50 (4%) |5/50 (10%) 10/50 (20%) 5/49 (10%) 8/50 (16%) | |POLY-3 RATE (b) | 3/42.07 3/45.64 5/41.75 2/48.01 |5/46.45 10/45.62 5/43.71 8/45.88 | |POLY-3 PERCENT (g) | 7.1% 6.6% 12.0% 4.2% |10.8% 21.9% 11.4% 17.4% | |TERMINAL (d) | 2/31 (7%) 2/36 (6%) 0/27 (0%) 1/41 (2%) |3/36 (8%) 6/33 (18%) 3/35 (9%) 3/33 (9%) | |FIRST INCIDENCE | 606 591 488 691 |632 626 610 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.349N P=0.595N P=0.328 P=0.382N |P=0.351 P=0.112 P=0.596 P=0.245 | |POLY 3 | P=0.373N P=0.624N P=0.351 P=0.440N |P=0.377 P=0.120 P=0.592 P=0.267 | |POLY 1.5 | P=0.401N P=0.643N P=0.348 P=0.465N |P=0.377 P=0.122 P=0.596 P=0.268 | |POLY 6 | P=0.341N P=0.601N P=0.355 P=0.410N |P=0.379 P=0.117 P=0.592 P=0.268 | |LOGISTIC REGRESSION| P=0.491N P=0.663 P=0.397 P=0.504N |P=0.395 P=0.127 P=0.622 P=0.311 | |COCH-ARM / FISHERS | P=0.442N P=0.661N P=0.357 P=0.500N |P=0.390 P=0.131 P=0.617 P=0.277 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |11/50 (22%) 17/50 (34%) 11/49 (22%) 7/50 (14%) | |POLY-3 RATE (b) | |11/45.91 17/45.91 11/42.98 7/44.36 | |POLY-3 PERCENT (g) | |24.0% 37.0% 25.6% 15.8% | |TERMINAL (d) | |11/36 (31%) 11/33 (33%) 11/35 (31%) 6/33 (18%) | |FIRST INCIDENCE | |735 (T) 620 735 (T) 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.105N P=0.092 P=0.570 P=0.276N | |POLY 3 | |P=0.092N P=0.126 P=0.527 P=0.239N | |POLY 1.5 | |P=0.089N P=0.124 P=0.537 P=0.234N | |POLY 6 | |P=0.096N P=0.130 P=0.525 P=0.243N | |LOGISTIC REGRESSION| |P=0.097N P=0.106 P=0.570 P=0.259N | |COCH-ARM / FISHERS | |P=0.079N P=0.133 P=0.574 P=0.218N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |9/50 (18%) 21/50 (42%) 15/49 (31%) 12/50 (24%) | |POLY-3 RATE (b) | |9/45.91 21/45.07 15/44.81 12/44.84 | |POLY-3 PERCENT (g) | |19.6% 46.6% 33.5% 26.8% | |TERMINAL (d) | |9/36 (25%) 19/33 (58%) 10/35 (29%) 10/33 (30%) | |FIRST INCIDENCE | |735 (T) 681 470 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.494 P=0.002 ** P=0.107 P=0.238 | |POLY 3 | |P=0.539 P=0.004 ** P=0.102 P=0.288 | |POLY 1.5 | |P=0.542N P=0.005 ** P=0.100 P=0.293 | |POLY 6 | |P=0.540 P=0.004 ** P=0.112 P=0.283 | |LOGISTIC REGRESSION| |P=0.519 P=0.003 ** P=0.094 P=0.260 | |COCH-ARM / FISHERS | |P=0.513N P=0.008 ** P=0.109 P=0.312 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |16/50 (32%) 7/50 (14%) 9/49 (18%) 11/50 (22%) | |POLY-3 RATE (b) | |16/45.91 7/44.80 9/44.09 11/44.91 | |POLY-3 PERCENT (g) | |34.9% 15.6% 20.4% 24.5% | |TERMINAL (d) | |16/36 (44%) 6/33 (18%) 7/35 (20%) 8/33 (24%) | |FIRST INCIDENCE | |735 (T) 718 177 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.325N P=0.041N* P=0.089N P=0.253N | |POLY 3 | |P=0.277N P=0.028N* P=0.095N P=0.196N | |POLY 1.5 | |P=0.278N P=0.029N* P=0.095N P=0.196N | |POLY 6 | |P=0.271N P=0.028N* P=0.091N P=0.193N | |LOGISTIC REGRESSION| |P=0.303N P=0.039N* P=0.105N P=0.229N | |COCH-ARM / FISHERS | |P=0.273N P=0.028N* P=0.091N P=0.184N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Epididymis | | Granuloma Sperm | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 6/49 (12%) 4/50 (8%) 5/50 (10%) | | |POLY-3 RATE (b) | 1/41.92 6/44.52 4/39.67 5/47.85 | | |POLY-3 PERCENT (g) | 2.4% 13.5% 10.1% 10.5% | | |TERMINAL (d) | 0/31 (0%) 5/36 (14%) 4/27 (15%) 5/41 (12%) | | |FIRST INCIDENCE | 655 680 731 (T) 731 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.313 P=0.094 P=0.147 P=0.183 | | |POLY 3 | P=0.263 P=0.066 P=0.161 P=0.135 | | |POLY 1.5 | P=0.231 P=0.059 P=0.166 P=0.121 | | |POLY 6 | P=0.304 P=0.075 P=0.153 P=0.155 | | |LOGISTIC REGRESSION| P=0.293 P=0.070 P=0.155 P=0.146 | | |COCH-ARM / FISHERS | P=0.193 P=0.053 P=0.181 P=0.102 | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Epididymis | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 2/50 (4%) 0/50 (0%) | | |POLY-3 RATE (b) | 0/41.64 0/44.33 2/39.67 0/47.85 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% | | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 2/27 (7%) 0/41 (0%) | | |FIRST INCIDENCE | --- --- 731 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.637 (e) P=0.208 (e) | | |POLY 3 | P=0.661 (e) P=0.226 (e) | | |POLY 1.5 | P=0.637 (e) P=0.229 (e) | | |POLY 6 | P=0.687 (e) P=0.222 (e) | | |LOGISTIC REGRESSION| (e) (e) P=0.208 (e) | | |COCH-ARM / FISHERS | P=0.596 (e) P=0.247 (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Eye: Lens | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 1/2 (50%) 1/1 (100%) 0/0 (0%) |0/0 (0%) 3/3 (100%) 0/1 (0%) 2/2 (100%) | |POLY-3 RATE (b) | 1/1.00 1/1.98 1/1.00 0/0.00 |0/0.00 3/3.00 0/0.70 2/2.00 | |POLY-3 PERCENT (g) | 100.0% 50.6% 100.0% 0.0% |0.0% 100.0% 0.0% 100.0% | |TERMINAL (d) | 1/1 (100%) 1/1 (100%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 2/2 (100%) 0/0 (0%) 2/2 (100%) | |FIRST INCIDENCE | 731 (T) 731 (T) 621 --- |--- 697 --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.716 P=1.000 (e) (e) |P=0.578N (e) (e) (e) | |POLY 3 | (e) P=0.619N (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) P=0.616N (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) P=0.625N (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.973N P=1.000 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.949 P=0.667N (e) (e) |P=0.752 (e) (e) (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Eye: Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 0/2 (0%) 1/1 (100%) 0/0 (0%) |0/0 (0%) 3/3 (100%) 0/1 (0%) 2/2 (100%) | |POLY-3 RATE (b) | 1/1.00 0/1.98 1/1.00 0/0.00 |0/0.00 3/3.00 0/0.70 2/2.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 100.0% 0.0% |0.0% 100.0% 0.0% 100.0% | |TERMINAL (d) | 1/1 (100%) 0/1 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 2/2 (100%) 0/0 (0%) 2/2 (100%) | |FIRST INCIDENCE | 731 (T) --- 621 --- |--- 697 --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.651N P=0.500N (e) (e) |P=0.578N (e) (e) (e) | |POLY 3 | (e) P<0.001N** (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) P<0.001N** (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) P<0.001N** (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.824N (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.921 P=0.333N (e) (e) |P=0.752 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 46/50 (92%) 46/50 (92%) 45/50 (90%) 50/50 (100%)|45/50 (90%) 45/50 (90%) 43/49 (88%) 44/50 (88%) | |POLY-3 RATE (b) | 46/50.00 46/49.42 45/47.34 50/50.00 |45/48.97 45/48.49 43/46.55 44/49.03 | |POLY-3 PERCENT (g) | 92.0% 93.1% 95.1% 100.0% |91.9% 92.8% 92.4% 89.7% | |TERMINAL (d) | 27/31 (87%) 35/36 (97%) 26/27 (96%) 41/41 (100%)|35/36 (97%) 33/33 (100%) 33/35 (94%) 29/33 (88%) | |FIRST INCIDENCE | 429 170 178 499 |523 561 459 172 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.150N P=0.177N P=0.350 P=0.098N |P=0.422 P=0.310 P=0.552N P=0.393 | |POLY 3 | P=0.030 * P=0.571 P=0.418 P=0.061 |P=0.380N P=0.590 P=0.625 P=0.492N | |POLY 1.5 | P=0.038 * P=0.606 P=0.532 P=0.061 |P=0.386N P=0.558 P=0.644 P=0.502N | |POLY 6 | P=0.025 * P=0.507 P=0.299 P=0.061 |P=0.342N P=0.650 P=0.646 P=0.454N | |LOGISTIC REGRESSION| P=0.084 P=0.593 P=0.597N (e) |P=0.504N P=0.532 P=0.562 P=0.545N | |COCH-ARM / FISHERS | P=0.066 P=0.643N P=0.500N P=0.059 |P=0.408N P=0.630N P=0.486N P=0.500N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | 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%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/41.64 0/45.17 2/40.25 1/47.94 |0/45.91 1/44.73 1/42.98 0/44.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 2.1% |0.0% 2.2% 2.3% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 1/33 (3%) 1/35 (3%) 0/33 (0%) | |FIRST INCIDENCE | --- --- 624 709 |--- 735 (T) 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.303 (e) P=0.230 P=0.559 |P=0.608N P=0.483 P=0.494 (e) | |POLY 3 | P=0.293 (e) P=0.229 P=0.528 |P=0.606N P=0.495 P=0.487 (e) | |POLY 1.5 | P=0.274 (e) P=0.230 P=0.516 |P=0.603N P=0.496 P=0.489 (e) | |POLY 6 | P=0.316 (e) P=0.228 P=0.542 |P=0.610N P=0.493 P=0.486 (e) | |LOGISTIC REGRESSION| P=0.229 (e) P=0.243 P=0.520 |(e) P=0.483 P=0.494 (e) | |COCH-ARM / FISHERS | P=0.246 (e) P=0.247 P=0.500 |P=0.595N P=0.500 P=0.495 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 3/42.74 0/45.17 1/40.04 0/47.85 |0/45.91 0/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 7.0% 0.0% 2.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 429 --- 624 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.075N P=0.106N P=0.335N P=0.092N |(e) (e) (e) (e) | |POLY 3 | P=0.083N P=0.109N P=0.328N P=0.100N |(e) (e) (e) (e) | |POLY 1.5 | P=0.084N P=0.114N P=0.323N P=0.108N |(e) (e) (e) (e) | |POLY 6 | P=0.083N P=0.102N P=0.336N P=0.091N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.090N P=0.111N P=0.246N P=0.278N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.086N P=0.121N P=0.309N P=0.121N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 1/50 (2%) 1/50 (2%) |5/50 (10%) 0/50 (0%) 4/49 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 4/42.07 3/45.17 1/39.67 1/47.85 |5/45.91 0/44.73 4/43.48 1/44.16 | |POLY-3 PERCENT (g) | 9.5% 6.6% 2.5% 2.1% |10.9% 0.0% 9.2% 2.3% | |TERMINAL (d) | 3/31 (10%) 3/36 (8%) 1/27 (4%) 1/41 (2%) |5/36 (14%) 0/33 (0%) 2/35 (6%) 1/33 (3%) | |FIRST INCIDENCE | 606 731 (T) 731 (T) 731 (T) |735 (T) --- 652 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.064N P=0.422N P=0.217N P=0.112N |P=0.183N P=0.040N* P=0.525N P=0.122N | |POLY 3 | P=0.080N P=0.461N P=0.196N P=0.142N |P=0.167N P=0.033N* P=0.534N P=0.110N | |POLY 1.5 | P=0.085N P=0.481N P=0.192N P=0.157N |P=0.165N P=0.032N* P=0.531N P=0.108N | |POLY 6 | P=0.073N P=0.437N P=0.203N P=0.126N |P=0.167N P=0.033N* P=0.529N P=0.113N | |LOGISTIC REGRESSION| P=0.069N P=0.444N P=0.196N P=0.150N |P=0.176N (e) P=0.540N P=0.122N | |COCH-ARM / FISHERS | P=0.092N P=0.500N P=0.181N P=0.181N |P=0.163N P=0.028N* P=0.513N P=0.102N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 8/50 (16%) 4/50 (8%) |4/50 (8%) 1/50 (2%) 3/49 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 4/42.07 5/45.25 8/39.87 4/48.01 |4/46.07 1/44.73 3/43.34 1/44.64 | |POLY-3 PERCENT (g) | 9.5% 11.1% 20.1% 8.3% |8.7% 2.2% 6.9% 2.2% | |TERMINAL (d) | 3/31 (10%) 4/36 (11%) 7/27 (26%) 3/41 (7%) |3/36 (8%) 1/33 (3%) 2/35 (6%) 0/33 (0%) | |FIRST INCIDENCE | 606 710 676 691 |695 735 (T) 632 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.413N P=0.591 P=0.124 P=0.489N |P=0.215N P=0.204N P=0.520N P=0.205N | |POLY 3 | P=0.479N P=0.546 P=0.148 P=0.569N |P=0.200N P=0.188N P=0.533N P=0.188N | |POLY 1.5 | P=0.519N P=0.523 P=0.156 P=0.600N |P=0.199N P=0.186N P=0.529N P=0.186N | |POLY 6 | P=0.429N P=0.574 P=0.137 P=0.530N |P=0.200N P=0.191N P=0.533N P=0.191N | |LOGISTIC REGRESSION| P=0.451N P=0.570 P=0.139 P=0.585N |P=0.197N P=0.193N P=0.530N P=0.173N | |COCH-ARM / FISHERS | P=0.547 P=0.500 P=0.178 P=0.643N |P=0.195N P=0.181N P=0.511N P=0.181N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/41.64 1/45.63 2/39.81 0/47.85 |0/45.91 1/44.73 0/42.98 1/44.70 | |POLY-3 PERCENT (g) | 0.0% 2.2% 5.0% 0.0% |0.0% 2.2% 0.0% 2.2% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 1/27 (4%) 0/41 (0%) |0/36 (0%) 1/33 (3%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 593 695 --- |--- 735 (T) --- 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.562N P=0.522 P=0.211 (e) |P=0.399 P=0.483 (e) P=0.500 | |POLY 3 | P=0.564N P=0.518 P=0.227 (e) |P=0.397 P=0.495 (e) P=0.495 | |POLY 1.5 | P=0.585N P=0.509 P=0.229 (e) |P=0.399 P=0.496 (e) P=0.496 | |POLY 6 | P=0.537N P=0.530 P=0.223 (e) |P=0.395 P=0.493 (e) P=0.493 | |LOGISTIC REGRESSION| P=0.630N P=0.513 P=0.221 (e) |P=0.420 P=0.483 (e) P=0.607 | |COCH-ARM / FISHERS | P=0.616N P=0.500 P=0.247 (e) |P=0.405 P=0.500 (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 31/50 (62%) 30/50 (60%) 32/50 (64%) 38/50 (76%) |38/50 (76%) 28/50 (56%) 33/49 (67%) 30/50 (60%) | |POLY-3 RATE (b) | 31/46.41 30/47.47 32/43.08 38/48.92 |38/48.65 28/47.76 33/47.91 30/46.96 | |POLY-3 PERCENT (g) | 66.8% 63.2% 74.3% 77.7% |78.1% 58.6% 68.9% 63.9% | |TERMINAL (d) | 20/31 (65%) 24/36 (67%) 23/27 (85%) 32/41 (78%) |29/36 (81%) 16/33 (49%) 22/35 (63%) 20/33 (61%) | |FIRST INCIDENCE | 499 404 560 633 |523 597 177 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.511 P=0.221N P=0.271 P=0.429N |P=0.304N P=0.137N P=0.328N P=0.225N | |POLY 3 | P=0.073 P=0.440N P=0.285 P=0.163 |P=0.179N P=0.029N* P=0.209N P=0.089N | |POLY 1.5 | P=0.064 P=0.474N P=0.347 P=0.132 |P=0.169N P=0.032N* P=0.223N P=0.085N | |POLY 6 | P=0.088 P=0.408N P=0.210 P=0.206 |P=0.187N P=0.024N* P=0.180N P=0.090N | |LOGISTIC REGRESSION| P=0.131 P=0.456N P=0.397 P=0.196 |P=0.153N P=0.033N* P=0.210N P=0.086N | |COCH-ARM / FISHERS | P=0.057 P=0.500N P=0.500 P=0.097 |P=0.145N P=0.028N* P=0.232N P=0.066N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 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%) 49/50 (98%) 44/50 (88%) 45/50 (90%) |43/50 (86%) 41/50 (82%) 38/49 (78%) 40/50 (80%) | |POLY-3 RATE (b) | 47/48.89 49/49.92 44/47.17 45/48.91 |43/49.75 41/46.75 38/47.48 40/47.17 | |POLY-3 PERCENT (g) | 96.1% 98.2% 93.3% 92.0% |86.4% 87.7% 80.0% 84.8% | |TERMINAL (d) | 31/31 (100%) 36/36 (100%) 27/27 (100%) 41/41 (100%)|31/36 (86%) 32/33 (97%) 28/35 (80%) 31/33 (94%) | |FIRST INCIDENCE | 429 170 178 499 |523 618 177 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.005N** P=0.240N P=0.451 P=0.002N** |P=0.498N P=0.486 P=0.338N P=0.558 | |POLY 3 | P=0.118N P=0.501 P=0.418N P=0.309N |P=0.385N P=0.548 P=0.280N P=0.526N | |POLY 1.5 | P=0.131N P=0.396 P=0.372N P=0.330N |P=0.336N P=0.596N P=0.248N P=0.445N | |POLY 6 | P=0.106N P=0.712 P=0.483N P=0.283N |P=0.459N P=0.408 P=0.316N P=0.611 | |LOGISTIC REGRESSION| P=0.075N P=0.314 P=0.366N P=0.146N |P=0.321N P=0.471N P=0.196N P=0.380N | |COCH-ARM / FISHERS | P=0.148N P=0.309 P=0.243N P=0.357N |P=0.258N P=0.393N P=0.204N P=0.298N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 26/50 (52%) 32/50 (64%) 23/50 (46%) 33/50 (66%) |44/50 (88%) 42/50 (84%) 43/49 (88%) 44/50 (88%) | |POLY-3 RATE (b) | 26/43.54 32/45.17 23/41.09 33/48.09 |44/48.51 42/46.49 43/46.53 44/48.22 | |POLY-3 PERCENT (g) | 59.7% 70.9% 56.0% 68.6% |90.7% 90.4% 92.4% 91.2% | |TERMINAL (d) | 21/31 (68%) 32/36 (89%) 20/27 (74%) 31/41 (76%) |34/36 (94%) 33/33 (100%) 34/35 (97%) 32/33 (97%) | |FIRST INCIDENCE | 577 731 (T) 488 691 |597 652 470 172 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.370N P=0.422 P=0.586 P=0.508N |P=0.269 P=0.472 P=0.533 P=0.306 | |POLY 3 | P=0.322 P=0.177 P=0.447N P=0.244 |P=0.508 P=0.627N P=0.530 P=0.612 | |POLY 1.5 | P=0.251 P=0.157 P=0.418N P=0.178 |P=0.506 P=0.544N P=0.543 P=0.622 | |POLY 6 | P=0.431 P=0.199 P=0.507N P=0.344 |P=0.501 P=0.565 P=0.524 P=0.575 | |LOGISTIC REGRESSION| P=0.456N P=0.465 P=0.445N P=0.527 |P=0.310 P=0.483N P=0.388 P=0.509 | |COCH-ARM / FISHERS | P=0.180 P=0.156 P=0.345N P=0.111 |P=0.473 P=0.387N P=0.606N P=0.620N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 3/50 (6%) |2/50 (4%) 2/50 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.64 0/45.17 0/39.67 3/47.85 |2/45.91 2/45.12 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 6.3% |4.4% 4.4% 0.0% 0.0% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 0/27 (0%) 3/41 (7%) |2/36 (6%) 1/33 (3%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) --- --- 731 (T) |735 (T) 626 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.128 P=0.470N P=0.528N P=0.409 |P=0.094N P=0.668 P=0.244N P=0.258N | |POLY 3 | P=0.089 P=0.484N P=0.510N P=0.357 |P=0.090N P=0.688 P=0.252N P=0.246N | |POLY 1.5 | P=0.087 P=0.492N P=0.508N P=0.335 |P=0.089N P=0.688 P=0.250N P=0.244N | |POLY 6 | P=0.091 P=0.474N P=0.513N P=0.385 |P=0.091N P=0.686 P=0.252N P=0.249N | |LOGISTIC REGRESSION| P=0.128 (e) (e) P=0.409 |P=0.089N P=0.693 (e) (e) | |COCH-ARM / FISHERS | P=0.086 P=0.500N P=0.500N P=0.309 |P=0.087N P=0.691N P=0.253N P=0.247N | |=================================================================================================================================| | | | | | | 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%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 1/42.07 0/45.17 2/39.67 0/47.85 |1/45.91 0/44.73 0/42.98 1/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 5.0% 0.0% |2.2% 0.0% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 2/27 (7%) 0/41 (0%) |1/36 (3%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 606 --- 731 (T) --- |735 (T) --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.412N P=0.477N P=0.465 P=0.464N |P=0.582 P=0.517N P=0.506N P=0.742 | |POLY 3 | P=0.432N P=0.486N P=0.479 P=0.474N |P=0.590 P=0.505N P=0.513N P=0.752 | |POLY 1.5 | P=0.442N P=0.493N P=0.485 P=0.485N |P=0.591 P=0.504N P=0.511N P=0.754 | |POLY 6 | P=0.419N P=0.477N P=0.471 P=0.462N |P=0.590 P=0.507N P=0.514N P=0.749 | |LOGISTIC REGRESSION| P=0.459N P=0.493N P=0.488 P=0.675N |P=0.582 (e) (e) P=0.742 | |COCH-ARM / FISHERS | P=0.461N P=0.500N P=0.500 P=0.500N |P=0.594 P=0.500N P=0.505N P=0.753N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |2/50 (4%) 3/50 (6%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.64 0/45.17 2/40.17 0/47.85 |2/45.91 3/45.33 0/42.98 1/44.51 | |POLY-3 PERCENT (g) | 2.4% 0.0% 5.0% 0.0% |4.4% 6.6% 0.0% 2.3% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 1/27 (4%) 0/41 (0%) |2/36 (6%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) --- 577 --- |735 (T) 652 --- 634 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.418N P=0.470N P=0.463 P=0.444N |P=0.259N P=0.482 P=0.244N P=0.523N | |POLY 3 | P=0.431N P=0.484N P=0.487 P=0.472N |P=0.251N P=0.494 P=0.252N P=0.511N | |POLY 1.5 | P=0.442N P=0.492N P=0.489 P=0.484N |P=0.250N P=0.493 P=0.250N P=0.508N | |POLY 6 | P=0.418N P=0.474N P=0.484 P=0.458N |P=0.253N P=0.495 P=0.252N P=0.513N | |LOGISTIC REGRESSION| P=0.468N (e) P=0.493 (e) |P=0.238N P=0.501 (e) P=0.498N | |COCH-ARM / FISHERS | P=0.461N P=0.500N P=0.500 P=0.500N |P=0.243N P=0.500 P=0.253N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 5/50 (10%) 4/50 (8%) |5/50 (10%) 12/50 (24%) 9/49 (18%) 7/50 (14%) | |POLY-3 RATE (b) | 2/41.64 1/45.17 5/39.87 4/47.85 |5/46.41 12/46.03 9/44.37 7/45.19 | |POLY-3 PERCENT (g) | 4.8% 2.2% 12.5% 8.4% |10.8% 26.1% 20.3% 15.5% | |TERMINAL (d) | 2/31 (7%) 1/36 (3%) 4/27 (15%) 4/41 (10%) |3/36 (8%) 8/33 (24%) 6/35 (17%) 5/33 (15%) | |FIRST INCIDENCE | 731 (T) 731 (T) 676 731 (T) |632 561 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.253 P=0.448N P=0.169 P=0.472 |P=0.487 P=0.046 * P=0.182 P=0.336 | |POLY 3 | P=0.203 P=0.472N P=0.197 P=0.403 |P=0.506 P=0.049 * P=0.167 P=0.360 | |POLY 1.5 | P=0.184 P=0.486N P=0.201 P=0.375 |P=0.513 P=0.050 P=0.169 P=0.365 | |POLY 6 | P=0.228 P=0.454N P=0.191 P=0.439 |P=0.497 P=0.048 * P=0.169 P=0.354 | |LOGISTIC REGRESSION| P=0.245 P=0.448N P=0.175 P=0.472 |P=0.542 P=0.054 P=0.194 P=0.390 | |COCH-ARM / FISHERS | P=0.157 P=0.500N P=0.218 P=0.339 |P=0.537 P=0.054 P=0.183 P=0.380 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 37/50 (74%) 38/50 (76%) 31/50 (62%) 39/50 (78%) |41/50 (82%) 42/50 (84%) 42/49 (86%) 43/50 (86%) | |POLY-3 RATE (b) | 37/45.01 38/47.71 31/43.52 39/48.31 |41/47.63 42/46.97 42/46.92 43/47.24 | |POLY-3 PERCENT (g) | 82.2% 79.7% 71.2% 80.7% |86.1% 89.4% 89.5% 91.0% | |TERMINAL (d) | 30/31 (97%) 33/36 (92%) 22/27 (82%) 36/41 (88%) |34/36 (94%) 32/33 (97%) 33/35 (94%) 32/33 (97%) | |FIRST INCIDENCE | 499 170 178 675 |620 618 177 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.057N P=0.203N P=0.407N P=0.034N* |P=0.187 P=0.235 P=0.373 P=0.168 | |POLY 3 | P=0.477N P=0.479N P=0.139N P=0.536N |P=0.272 P=0.421 P=0.416 P=0.317 | |POLY 1.5 | P=0.543 P=0.564N P=0.146N P=0.564 |P=0.279 P=0.424 P=0.407 P=0.321 | |POLY 6 | P=0.360N P=0.384N P=0.143N P=0.386N |P=0.283 P=0.410 P=0.449 P=0.327 | |LOGISTIC REGRESSION| P=0.373N P=0.550N P=0.197N P=0.174N |P=0.189 P=0.372 P=0.255 P=0.193 | |COCH-ARM / FISHERS | P=0.447 P=0.500 P=0.142N P=0.408 |P=0.336 P=0.500 P=0.410 P=0.393 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 32/50 (64%) 20/50 (40%) 32/50 (64%) |25/50 (50%) 24/50 (48%) 27/49 (55%) 20/50 (40%) | |POLY-3 RATE (b) | 29/42.61 32/45.19 20/39.67 32/47.85 |25/46.88 24/45.89 27/42.98 20/45.15 | |POLY-3 PERCENT (g) | 68.1% 70.8% 50.4% 66.9% |53.3% 52.3% 62.8% 44.3% | |TERMINAL (d) | 26/31 (84%) 31/36 (86%) 20/27 (74%) 32/41 (78%) |21/36 (58%) 21/33 (64%) 27/35 (77%) 17/33 (52%) | |FIRST INCIDENCE | 577 725 731 (T) 731 (T) |620 561 735 (T) 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.070N P=0.443N P=0.093N P=0.126N |P=0.277N P=0.506 P=0.339 P=0.332N | |POLY 3 | P=0.404N P=0.480 P=0.064N P=0.543N |P=0.244N P=0.544N P=0.237 P=0.252N | |POLY 1.5 | P=0.506N P=0.398 P=0.064N P=0.508 |P=0.228N P=0.536N P=0.281 P=0.241N | |POLY 6 | P=0.271N P=0.597 P=0.070N P=0.376N |P=0.264N P=0.567N P=0.197 P=0.272N | |LOGISTIC REGRESSION| P=0.074N P=0.329N P=0.062N P=0.130N |P=0.263N P=0.565N P=0.274 P=0.273N | |COCH-ARM / FISHERS | P=0.452 P=0.341 P=0.055N P=0.341 |P=0.198N P=0.500N P=0.380 P=0.211N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 2/50 (4%) 3/50 (6%) 5/50 (10%) |3/50 (6%) 4/50 (8%) 1/49 (2%) 6/50 (12%) | |POLY-3 RATE (b) | 5/43.41 2/45.59 3/40.54 5/48.49 |3/46.16 4/45.93 1/43.57 6/45.13 | |POLY-3 PERCENT (g) | 11.5% 4.4% 7.4% 10.3% |6.5% 8.7% 2.3% 13.3% | |TERMINAL (d) | 2/31 (7%) 0/36 (0%) 1/27 (4%) 2/41 (5%) |1/36 (3%) 1/33 (3%) 0/35 (0%) 3/33 (9%) | |FIRST INCIDENCE | 429 672 593 633 |670 561 543 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.562 P=0.172N P=0.399N P=0.478N |P=0.186 P=0.474 P=0.330N P=0.218 | |POLY 3 | P=0.488 P=0.196N P=0.394N P=0.559N |P=0.189 P=0.497 P=0.326N P=0.231 | |POLY 1.5 | P=0.471 P=0.208N P=0.385N P=0.590N |P=0.191 P=0.495 P=0.324N P=0.233 | |POLY 6 | P=0.512 P=0.181N P=0.405N P=0.518N |P=0.187 P=0.498 P=0.326N P=0.228 | |LOGISTIC REGRESSION| P=0.385 P=0.225N P=0.296N P=0.350 |P=0.216 P=0.540 P=0.269N P=0.251 | |COCH-ARM / FISHERS | P=0.446 P=0.218N P=0.357N P=0.630N |P=0.199 P=0.500 P=0.316N P=0.243 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 46/50 (92%) 45/50 (90%) 43/50 (86%) 43/50 (86%) |25/50 (50%) 28/50 (56%) 21/49 (43%) 18/50 (36%) | |POLY-3 RATE (b) | 46/48.14 45/47.58 43/45.90 43/48.57 |25/47.53 28/46.32 21/44.14 18/45.43 | |POLY-3 PERCENT (g) | 95.6% 94.6% 93.7% 88.5% |52.6% 60.5% 47.6% 39.6% | |TERMINAL (d) | 31/31 (100%) 36/36 (100%) 27/27 (100%) 39/41 (95%) |19/36 (53%) 21/33 (64%) 17/35 (49%) 13/33 (39%) | |FIRST INCIDENCE | 429 591 488 633 |597 597 610 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004N** P=0.090N P=0.450 P<0.001N** |P=0.091N P=0.231 P=0.344N P=0.213N | |POLY 3 | P=0.075N P=0.620N P=0.528N P=0.156N |P=0.057N P=0.285 P=0.392N P=0.145N | |POLY 1.5 | P=0.113N P=0.620N P=0.472N P=0.201N |P=0.052N P=0.298 P=0.370N P=0.135N | |POLY 6 | P=0.040N* P=0.583N P=0.577N P=0.107N |P=0.063N P=0.261 P=0.406N P=0.158N | |LOGISTIC REGRESSION| P=0.016N* P=0.334N P=0.418N P=0.036N* |P=0.058N P=0.295 P=0.379N P=0.140N | |COCH-ARM / FISHERS | P=0.194N P=0.500N P=0.262N P=0.262N |P=0.043N* P=0.344 P=0.305N P=0.113N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Hepatocyte | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 3/50 (6%) 4/50 (8%) 5/50 (10%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 7/41.73 3/45.17 4/39.67 5/47.85 |1/46.31 0/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 16.8% 6.6% 10.1% 10.5% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/31 (19%) 3/36 (8%) 4/27 (15%) 5/41 (12%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 707 731 (T) 731 (T) 731 (T) |620 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.277N P=0.104N P=0.344N P=0.203N |P=0.317N P=0.504N P=0.522N P=0.513N | |POLY 3 | P=0.371N P=0.126N P=0.288N P=0.287N |P=0.302N P=0.507N P=0.515N P=0.510N | |POLY 1.5 | P=0.391N P=0.141N P=0.283N P=0.325N |P=0.304N P=0.505N P=0.512N P=0.507N | |POLY 6 | P=0.347N P=0.108N P=0.299N P=0.244N |P=0.299N P=0.510N P=0.516N P=0.513N | |LOGISTIC REGRESSION| P=0.279N P=0.095N P=0.332N P=0.199N |P=0.288N P=0.451N P=0.440N P=0.441N | |COCH-ARM / FISHERS | P=0.419N P=0.159N P=0.262N P=0.380N |P=0.306N P=0.500N P=0.505N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 2/50 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.09 1/45.33 2/39.67 1/47.85 |1/45.91 2/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 2.2% 5.0% 2.1% |2.2% 4.5% 0.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 2/27 (7%) 1/41 (2%) |1/36 (3%) 2/33 (6%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 598 690 731 (T) 731 (T) |735 (T) 735 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.574N P=0.732N P=0.462 P=0.712N |P=0.198N P=0.470 P=0.506N P=0.517N | |POLY 3 | P=0.613N P=0.744N P=0.479 P=0.731N |P=0.196N P=0.491 P=0.513N P=0.508N | |POLY 1.5 | P=0.621 P=0.752N P=0.485 P=0.744N |P=0.194N P=0.493 P=0.511N P=0.506N | |POLY 6 | P=0.596N P=0.733N P=0.470 P=0.716N |P=0.198N P=0.487 P=0.514N P=0.510N | |LOGISTIC REGRESSION| P=0.602 P=0.759 P=0.489 P=0.708 |P=0.198N P=0.470 (e) (e) | |COCH-ARM / FISHERS | P=0.591 P=0.753N P=0.500 P=0.753N |P=0.189N P=0.500 P=0.505N P=0.500N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 37/50 (74%) 36/50 (72%) 32/50 (64%) 34/50 (68%) |32/50 (64%) 25/50 (50%) 14/49 (29%) 18/50 (36%) | |POLY-3 RATE (b) | 37/45.78 36/46.57 32/45.57 34/48.42 |32/47.61 25/47.59 14/44.67 18/46.08 | |POLY-3 PERCENT (g) | 80.8% 77.3% 70.2% 70.2% |67.2% 52.5% 31.3% 39.1% | |TERMINAL (d) | 26/31 (84%) 31/36 (86%) 19/27 (70%) 31/41 (76%) |26/36 (72%) 16/33 (49%) 9/35 (26%) 10/33 (30%) | |FIRST INCIDENCE | 505 593 178 672 |523 561 459 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019N* P=0.138N P=0.478N P=0.012N* |P=0.011N* P=0.244N P<0.001N** P=0.025N* | |POLY 3 | P=0.115N P=0.433N P=0.159N P=0.160N |P=0.002N** P=0.100N P<0.001N** P=0.004N** | |POLY 1.5 | P=0.162N P=0.482N P=0.180N P=0.221N |P=0.002N** P=0.113N P<0.001N** P=0.004N** | |POLY 6 | P=0.075N P=0.380N P=0.151N P=0.106N |P=0.002N** P=0.086N P<0.001N** P=0.004N** | |LOGISTIC REGRESSION| P=0.115N P=0.245N P=0.250N P=0.064N |P=0.003N** P=0.128N P<0.001N** P=0.006N** | |COCH-ARM / FISHERS | P=0.258N P=0.500N P=0.194N P=0.330N |P=0.002N** P=0.113N P<0.001N** P=0.004N** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/41.64 0/45.17 0/39.67 2/47.85 |0/45.91 0/44.73 0/42.98 1/44.19 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.2% |0.0% 0.0% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 2/41 (5%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- --- --- 731 (T) |--- --- --- 726 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.068 (e) (e) P=0.302 |P=0.194 (e) (e) P=0.483 | |POLY 3 | P=0.050 (e) (e) P=0.270 |P=0.195 (e) (e) P=0.492 | |POLY 1.5 | P=0.048 * (e) (e) P=0.256 |P=0.197 (e) (e) P=0.494 | |POLY 6 | P=0.052 (e) (e) P=0.287 |P=0.194 (e) (e) P=0.490 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.302 |P=0.194 (e) (e) P=0.489 | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |P=0.199 (e) (e) P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 32/50 (64%) 31/50 (62%) 27/50 (54%) 36/50 (72%) |36/50 (72%) 40/50 (80%) 37/49 (76%) 33/50 (66%) | |POLY-3 RATE (b) | 32/44.20 31/46.00 27/43.37 36/48.82 |36/46.90 40/46.90 37/45.83 33/46.22 | |POLY-3 PERCENT (g) | 72.4% 67.4% 62.3% 73.7% |76.8% 85.3% 80.7% 71.4% | |TERMINAL (d) | 27/31 (87%) 30/36 (83%) 20/27 (74%) 33/41 (81%) |32/36 (89%) 31/33 (94%) 31/35 (89%) 26/33 (79%) | |FIRST INCIDENCE | 499 404 123 499 |620 620 177 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.259N P=0.124N P=0.453N P=0.177N |P=0.351N P=0.083 P=0.393 P=0.574N | |POLY 3 | P=0.422 P=0.380N P=0.199N P=0.537 |P=0.182N P=0.199 P=0.410 P=0.355N | |POLY 1.5 | P=0.333 P=0.444N P=0.199N P=0.410 |P=0.191N P=0.195 P=0.417 P=0.362N | |POLY 6 | P=0.550N P=0.309N P=0.213N P=0.504N |P=0.166N P=0.209 P=0.414 P=0.340N | |LOGISTIC REGRESSION| P=0.426 P=0.219N P=0.267N P=0.477N |P=0.266N P=0.124 P=0.288 P=0.473N | |COCH-ARM / FISHERS | P=0.229 P=0.500N P=0.208N P=0.260 |P=0.184N P=0.241 P=0.433 P=0.333N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 46/50 (92%) 47/50 (94%) 48/50 (96%) 49/50 (98%) |45/50 (90%) 47/50 (94%) 45/49 (92%) 44/50 (88%) | |POLY-3 RATE (b) | 46/48.78 47/49.72 48/49.93 49/50.00 |45/49.83 47/48.70 45/48.14 44/49.22 | |POLY-3 PERCENT (g) | 94.3% 94.5% 96.1% 98.0% |90.3% 96.5% 93.5% 89.4% | |TERMINAL (d) | 30/31 (97%) 35/36 (97%) 26/27 (96%) 40/41 (98%) |32/36 (89%) 32/33 (97%) 33/35 (94%) 29/33 (88%) | |FIRST INCIDENCE | 429 170 123 499 |523 561 177 172 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.106N P=0.201N P=0.187 P=0.055N |P=0.460 P=0.225 P=0.442 P=0.407 | |POLY 3 | P=0.206 P=0.664 P=0.519 P=0.317 |P=0.366N P=0.197 P=0.418 P=0.574N | |POLY 1.5 | P=0.158 P=0.588 P=0.429 P=0.242 |P=0.336N P=0.214 P=0.450 P=0.542N | |POLY 6 | P=0.302 P=0.635N P=0.660 P=0.468 |P=0.406N P=0.180 P=0.397 P=0.612N | |LOGISTIC REGRESSION| P=0.113 P=0.514 P=0.337 P=0.277 |P=0.373N P=0.263 P=0.504 P=0.487N | |COCH-ARM / FISHERS | P=0.114 P=0.500 P=0.339 P=0.181 |P=0.337N P=0.357 P=0.513 P=0.500N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 35/50 (70%) 32/50 (64%) 23/50 (46%) 35/50 (70%) |47/50 (94%) 44/50 (88%) 44/49 (90%) 44/50 (88%) | |POLY-3 RATE (b) | 35/44.21 32/46.43 23/41.35 35/49.12 |47/49.18 44/47.80 44/46.70 44/46.78 | |POLY-3 PERCENT (g) | 79.2% 68.9% 55.6% 71.3% |95.6% 92.1% 94.2% 94.1% | |TERMINAL (d) | 29/31 (94%) 28/36 (78%) 18/27 (67%) 30/41 (73%) |36/36 (100%) 31/33 (94%) 34/35 (97%) 33/33 (100%) | |FIRST INCIDENCE | 505 591 488 499 |526 597 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.064N P=0.056N P=0.047N* P=0.038N* |P=0.511 P=0.548 P=0.474N P=0.529 | |POLY 3 | P=0.284N P=0.176N P=0.010N* P=0.250N |P=0.535N P=0.374N P=0.574N P=0.560N | |POLY 1.5 | P=0.379N P=0.257N P=0.012N* P=0.390N |P=0.415N P=0.350N P=0.505N P=0.426N | |POLY 6 | P=0.174N P=0.091N P=0.008N** P=0.114N |P=0.493 P=0.417N P=0.663N P=0.737 | |LOGISTIC REGRESSION| P=0.150N P=0.082N P=0.013N* P=0.152N |P=0.423N P=0.295N P=0.610N P=0.415N | |COCH-ARM / FISHERS | P=0.510N P=0.335N P=0.013N* P=0.586N |P=0.261N P=0.243N P=0.346N P=0.243N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 10/50 (20%) 9/50 (18%) 11/50 (22%) |12/50 (24%) 15/50 (30%) 13/49 (27%) 9/50 (18%) | |POLY-3 RATE (b) | 10/42.66 10/45.17 9/39.87 11/48.09 |12/45.91 15/44.87 13/42.98 9/44.77 | |POLY-3 PERCENT (g) | 23.4% 22.1% 22.6% 22.9% |26.1% 33.4% 30.3% 20.1% | |TERMINAL (d) | 8/31 (26%) 10/36 (28%) 8/27 (30%) 9/41 (22%) |12/36 (33%) 14/33 (42%) 13/35 (37%) 6/33 (18%) | |FIRST INCIDENCE | 577 731 (T) 676 691 |735 (T) 701 735 (T) 634 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.404N P=0.458N P=0.586 P=0.428N |P=0.240N P=0.225 P=0.465 P=0.389N | |POLY 3 | P=0.544N P=0.543N P=0.567N P=0.573N |P=0.213N P=0.297 P=0.423 P=0.333N | |POLY 1.5 | P=0.514 P=0.573N P=0.548N P=0.572 |P=0.212N P=0.303 P=0.435 P=0.330N | |POLY 6 | P=0.488N P=0.507N P=0.595N P=0.510N |P=0.210N P=0.285 P=0.419 P=0.333N | |LOGISTIC REGRESSION| P=0.449N P=0.483N P=0.565N P=0.555N |P=0.231N P=0.227 P=0.465 P=0.364N | |COCH-ARM / FISHERS | P=0.452 P=0.598N P=0.500N P=0.500 |P=0.197N P=0.326 P=0.477 P=0.312N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 36/50 (72%) 32/50 (64%) 24/50 (48%) 35/50 (70%) |47/50 (94%) 44/50 (88%) 44/49 (90%) 45/50 (90%) | |POLY-3 RATE (b) | 36/44.90 32/46.43 24/41.35 35/49.12 |47/49.18 44/47.80 44/46.70 45/47.04 | |POLY-3 PERCENT (g) | 80.2% 68.9% 58.0% 71.3% |95.6% 92.1% 94.2% 95.7% | |TERMINAL (d) | 29/31 (94%) 28/36 (78%) 19/27 (70%) 30/41 (73%) |36/36 (100%) 31/33 (94%) 34/35 (97%) 33/33 (100%) | |FIRST INCIDENCE | 499 591 488 499 |526 597 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.047N* P=0.038N* P=0.051N P=0.026N* |P=0.423 P=0.548 P=0.474N P=0.443 | |POLY 3 | P=0.250N P=0.144N P=0.013N* P=0.211N |P=0.487 P=0.374N P=0.574N P=0.713 | |POLY 1.5 | P=0.334N P=0.206N P=0.014N* P=0.327N |P=0.576N P=0.350N P=0.505N P=0.592N | |POLY 6 | P=0.154N P=0.077N P=0.013N* P=0.097N |P=0.350 P=0.417N P=0.663N P=0.600 | |LOGISTIC REGRESSION| P=0.131N P=0.076N P=0.013N* P=0.157N |P=0.564 P=0.295N P=0.610N P=0.583N | |COCH-ARM / FISHERS | P=0.451N P=0.260N P=0.012N* P=0.500N |P=0.387N P=0.243N P=0.346N P=0.357N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 11/50 (22%) 11/50 (22%) 7/50 (14%) |17/50 (34%) 21/50 (42%) 20/50 (40%) 21/50 (42%) | |POLY-3 RATE (b) | 10/43.05 11/45.17 11/40.13 7/47.85 |17/46.09 21/45.71 20/43.95 21/45.03 | |POLY-3 PERCENT (g) | 23.2% 24.4% 27.4% 14.6% |36.9% 45.9% 45.5% 46.6% | |TERMINAL (d) | 7/31 (23%) 11/36 (31%) 10/27 (37%) 7/41 (17%) |16/36 (44%) 17/33 (52%) 17/35 (49%) 17/33 (52%) | |FIRST INCIDENCE | 499 731 (T) 593 731 (T) |690 618 470 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.093N P=0.550N P=0.378 P=0.132N |P=0.204 P=0.168 P=0.294 P=0.169 | |POLY 3 | P=0.151N P=0.550 P=0.426 P=0.218N |P=0.238 P=0.250 P=0.267 P=0.229 | |POLY 1.5 | P=0.180N P=0.523 P=0.447 P=0.250N |P=0.251 P=0.249 P=0.275 P=0.239 | |POLY 6 | P=0.120N P=0.583 P=0.393 P=0.183N |P=0.227 P=0.248 P=0.270 P=0.219 | |LOGISTIC REGRESSION| P=0.125N P=0.588 P=0.445 P=0.244N |P=0.213 P=0.202 P=0.240 P=0.187 | |COCH-ARM / FISHERS | P=0.225N P=0.500 P=0.500 P=0.298N |P=0.287 P=0.268 P=0.339 P=0.268 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 10/50 (20%) 12/50 (24%) 12/50 (24%) |20/50 (40%) 21/50 (42%) 20/50 (40%) 22/50 (44%) | |POLY-3 RATE (b) | 10/42.91 10/45.17 12/39.67 12/47.85 |20/46.39 21/46.05 20/43.95 22/45.03 | |POLY-3 PERCENT (g) | 23.3% 22.1% 30.3% 25.1% |43.1% 45.6% 45.5% 48.9% | |TERMINAL (d) | 7/31 (23%) 10/36 (28%) 12/27 (44%) 12/41 (29%) |18/36 (50%) 17/33 (52%) 17/35 (49%) 18/33 (55%) | |FIRST INCIDENCE | 499 731 (T) 731 (T) 731 (T) |652 618 470 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.515N P=0.452N P=0.275 P=0.504N |P=0.294 P=0.368 P=0.533 P=0.288 | |POLY 3 | P=0.423 P=0.549N P=0.320 P=0.519 |P=0.330 P=0.487 P=0.493 P=0.365 | |POLY 1.5 | P=0.381 P=0.576N P=0.346 P=0.471 |P=0.349 P=0.481 P=0.504 P=0.380 | |POLY 6 | P=0.477 P=0.517N P=0.280 P=0.576 |P=0.309 P=0.491 P=0.493 P=0.346 | |LOGISTIC REGRESSION| P=0.536 P=0.508N P=0.331 P=0.551 |P=0.313 P=0.443 P=0.466 P=0.322 | |COCH-ARM / FISHERS | P=0.322 P=0.598N P=0.405 P=0.405 |P=0.395 P=0.500 P=0.581N P=0.420 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 4/50 (8%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/41.64 1/45.17 0/39.67 0/47.85 |0/45.91 4/45.04 1/43.08 2/44.77 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |0.0% 8.9% 2.3% 4.5% | |TERMINAL (d) | 0/31 (0%) 1/36 (3%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 3/33 (9%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | --- 731 (T) --- --- |--- 652 709 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.530N P=0.530 (e) (e) |P=0.404 P=0.056 P=0.500 P=0.232 | |POLY 3 | P=0.551N P=0.516 (e) (e) |P=0.406 P=0.058 P=0.487 P=0.232 | |POLY 1.5 | P=0.560N P=0.508 (e) (e) |P=0.409 P=0.058 P=0.489 P=0.233 | |POLY 6 | P=0.538N P=0.526 (e) (e) |P=0.402 P=0.057 P=0.487 P=0.230 | |LOGISTIC REGRESSION| (e) P=0.530 (e) (e) |P=0.426 P=0.060 P=0.492 P=0.278 | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.423 P=0.059 P=0.500 P=0.247 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node: Deep Cervical | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/20 (0%) 4/28 (14%) 4/28 (14%) 2/20 (10%) |0/25 (0%) 1/26 (4%) 3/24 (13%) 0/27 (0%) | |POLY-3 RATE (b) | 0/16.32 4/25.68 4/24.19 2/19.69 |0/23.04 1/23.53 3/21.65 0/24.77 | |POLY-3 PERCENT (g) | 0.0% 15.6% 16.5% 10.2% |0.0% 4.3% 13.9% 0.0% | |TERMINAL (d) | 0/11 (0%) 4/19 (21%) 3/18 (17%) 1/17 (6%) |0/19 (0%) 0/17 (0%) 1/17 (6%) 0/20 (0%) | |FIRST INCIDENCE | --- 731 (T) 677 675 |--- 675 632 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.493 P=0.145 P=0.113 P=0.327 |P=0.628 P=0.486 P=0.114 (e) | |POLY 3 | P=0.434 P=0.128 P=0.114 P=0.278 |P=0.618N P=0.504 P=0.101 (e) | |POLY 1.5 | P=0.384 P=0.118 P=0.110 P=0.258 |P=0.618N P=0.506 P=0.103 (e) | |POLY 6 | P=0.506 P=0.140 P=0.120 P=0.306 |P=0.616N P=0.501 P=0.102 (e) | |LOGISTIC REGRESSION| P=0.430 P=0.145 P=0.121 P=0.227 |P=0.614N P=0.517 P=0.115 (e) | |COCH-ARM / FISHERS | P=0.320 P=0.105 P=0.105 P=0.244 |P=0.615N P=0.510 P=0.110 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node: Deep Cervical | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/20 (5%) 4/28 (14%) 4/28 (14%) 3/20 (15%) |0/25 (0%) 1/26 (4%) 3/24 (13%) 3/27 (11%) | |POLY-3 RATE (b) | 1/16.32 4/25.68 4/24.17 3/19.69 |0/23.04 1/23.53 3/21.65 3/25.12 | |POLY-3 PERCENT (g) | 6.1% 15.6% 16.6% 15.2% |0.0% 4.3% 13.9% 11.9% | |TERMINAL (d) | 1/11 (9%) 4/19 (21%) 3/18 (17%) 2/17 (12%) |0/19 (0%) 0/17 (0%) 1/17 (6%) 2/20 (10%) | |FIRST INCIDENCE | 731 (T) 731 (T) 682 675 |--- 675 632 634 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.475 P=0.370 P=0.302 P=0.460 |P=0.074 P=0.486 P=0.114 P=0.124 | |POLY 3 | P=0.382 P=0.336 P=0.310 P=0.372 |P=0.077 P=0.504 P=0.101 P=0.130 | |POLY 1.5 | P=0.340 P=0.316 P=0.301 P=0.341 |P=0.076 P=0.506 P=0.103 P=0.129 | |POLY 6 | P=0.444 P=0.358 P=0.322 P=0.415 |P=0.080 P=0.501 P=0.102 P=0.132 | |LOGISTIC REGRESSION| P=0.419 P=0.370 P=0.322 P=0.386 |P=0.074 P=0.517 P=0.115 P=0.132 | |COCH-ARM / FISHERS | P=0.287 P=0.297 P=0.297 P=0.302 |P=0.075 P=0.510 P=0.110 P=0.132 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |4/50 (8%) 3/50 (6%) 3/49 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 0/41.64 0/45.17 0/39.67 0/47.85 |4/46.28 3/44.73 3/42.98 0/44.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |8.6% 6.7% 7.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |3/36 (8%) 3/33 (9%) 3/35 (9%) 0/33 (0%) | |FIRST INCIDENCE | --- --- --- --- |632 735 (T) 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.057N P=0.544N P=0.520N P=0.075N | |POLY 3 | (e) (e) (e) (e) |P=0.056N P=0.518N P=0.540N P=0.066N | |POLY 1.5 | (e) (e) (e) (e) |P=0.054N P=0.514N P=0.533N P=0.065N | |POLY 6 | (e) (e) (e) (e) |P=0.057N P=0.527N P=0.545N P=0.069N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.056N P=0.516N P=0.535N P=0.064N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.051N P=0.500N P=0.511N P=0.059N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 47/50 (94%) 41/50 (82%) 45/50 (90%) 47/50 (94%) |47/50 (94%) 45/50 (90%) 37/49 (76%) 42/50 (84%) | |POLY-3 RATE (b) | 47/49.57 41/49.84 45/47.44 47/49.41 |47/49.06 45/47.91 37/44.84 42/48.75 | |POLY-3 PERCENT (g) | 94.8% 82.3% 94.9% 95.1% |95.8% 93.9% 82.5% 86.2% | |TERMINAL (d) | 29/31 (94%) 28/36 (78%) 26/27 (96%) 41/41 (100%)|35/36 (97%) 33/33 (100%) 30/35 (86%) 27/33 (82%) | |FIRST INCIDENCE | 429 170 488 499 |526 597 498 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.093N P=0.037N* P=0.402 P=0.015N* |P=0.309N P=0.463 P=0.066N P=0.462N | |POLY 3 | P=0.232 P=0.045N* P=0.681 P=0.662 |P=0.036N* P=0.518N P=0.026N* P=0.086N | |POLY 1.5 | P=0.258 P=0.051N P=0.640N P=0.665 |P=0.048N* P=0.491N P=0.018N* P=0.102N | |POLY 6 | P=0.190 P=0.040N* P=0.674 P=0.637 |P=0.023N* P=0.576N P=0.040N* P=0.066N | |LOGISTIC REGRESSION| P=0.386 P=0.091N P=0.527N P=0.608N |P=0.104N P=0.427N P=0.028N* P=0.148N | |COCH-ARM / FISHERS | P=0.316 P=0.061N P=0.357N P=0.661N |P=0.065N P=0.357N P=0.010N* P=0.100N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/5 (40%) 3/8 (38%) 6/9 (67%) 9/12 (75%) |8/9 (89%) 4/6 (67%) 8/9 (89%) 7/8 (88%) | |POLY-3 RATE (b) | 2/4.43 3/7.30 6/7.62 9/11.76 |8/8.83 4/5.76 8/9.00 7/8.00 | |POLY-3 PERCENT (g) | 45.1% 41.1% 78.8% 76.6% |90.6% 69.4% 88.9% 87.5% | |TERMINAL (d) | 2/3 (67%) 3/5 (60%) 6/6 (100%) 8/10 (80%) |6/6 (100%) 1/2 (50%) 6/7 (86%) 7/8 (88%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 691 |597 675 613 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.191 P=0.702N P=0.362 P=0.390 |P=0.158N P=0.599N P=0.539N P=0.152N | |POLY 3 | P=0.081 P=0.673N P=0.269 P=0.270 |P=0.590 P=0.366N P=0.741N P=0.714N | |POLY 1.5 | P=0.071 P=0.674N P=0.304 P=0.238 |P=0.561 P=0.359N P=0.751N P=0.724N | |POLY 6 | P=0.109 P=0.671N P=0.229 P=0.335 |P=0.637N P=0.380N P=0.719N P=0.692N | |LOGISTIC REGRESSION| P=0.205 P=0.702N P=0.362 P=0.463 |P=0.563 P=0.349N P=0.774N P=0.721N | |COCH-ARM / FISHERS | P=0.064 P=0.685N P=0.343 P=0.205 |P=0.532 P=0.341N P=0.765N P=0.735N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/5 (40%) 2/8 (25%) 5/9 (56%) 6/12 (50%) |5/9 (56%) 2/6 (33%) 5/9 (56%) 3/8 (38%) | |POLY-3 RATE (b) | 2/4.43 2/7.30 5/7.62 6/11.60 |5/8.36 2/5.61 5/8.38 3/8.00 | |POLY-3 PERCENT (g) | 45.1% 27.4% 65.6% 51.7% |59.8% 35.6% 59.7% 37.5% | |TERMINAL (d) | 2/3 (67%) 2/5 (40%) 5/6 (83%) 6/10 (60%) |4/6 (67%) 0/2 (0%) 5/7 (71%) 3/8 (38%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 731 (T) |690 675 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.568 P=0.500N P=0.605 P=0.674N |P=0.133N P=0.514N P=0.566N P=0.183N | |POLY 3 | P=0.351 P=0.506N P=0.463 P=0.620 |P=0.330N P=0.369N P=0.686N P=0.346N | |POLY 1.5 | P=0.324 P=0.511N P=0.477 P=0.591 |P=0.358N P=0.373N P=0.680N P=0.371N | |POLY 6 | P=0.404 P=0.496N P=0.460 P=0.667 |P=0.287N P=0.370N P=0.696 P=0.309N | |LOGISTIC REGRESSION| P=0.568 P=0.500N P=0.605 P=0.674N |P=0.205N P=0.408N P=0.641N P=0.256N | |COCH-ARM / FISHERS | P=0.292 P=0.510N P=0.500 P=0.563 |P=0.384N P=0.378N P=0.681N P=0.399N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/5 (40%) 3/8 (38%) 8/9 (89%) 10/12 (83%) |7/9 (78%) 5/6 (83%) 9/9 (100%) 7/8 (88%) | |POLY-3 RATE (b) | 2/4.43 3/7.30 8/8.51 10/11.76 |7/8.83 5/5.76 9/9.00 7/8.00 | |POLY-3 PERCENT (g) | 45.1% 41.1% 94.0% 85.1% |79.3% 86.8% 100.0% 87.5% | |TERMINAL (d) | 2/3 (67%) 3/5 (60%) 6/6 (100%) 9/10 (90%) |5/6 (83%) 2/2 (100%) 7/7 (100%) 7/8 (88%) | |FIRST INCIDENCE | 731 (T) 731 (T) 535 691 |597 675 613 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.102 P=0.702N P=0.085 P=0.270 |P=0.197N P=0.401 P=0.461 P=0.373N | |POLY 3 | P=0.022 * P=0.673N P=0.055 P=0.144 |P=0.418 P=0.629 P=0.245 P=0.578 | |POLY 1.5 | P=0.019 * P=0.674N P=0.062 P=0.123 |P=0.391 P=0.636 P=0.235 P=0.561 | |POLY 6 | P=0.033 * P=0.671N P=0.056 P=0.192 |P=0.472 P=0.616 P=0.268 P=0.609 | |LOGISTIC REGRESSION| P=0.047 * P=0.702N P=0.052 P=0.328 |P=0.412 P=0.651 P=0.226 P=0.562 | |COCH-ARM / FISHERS | P=0.025 * P=0.685N P=0.095 P=0.117 |P=0.361 P=0.659 P=0.235 P=0.547 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 4/50 (8%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/42.52 1/45.17 4/39.67 3/48.53 |0/45.91 0/44.73 0/42.98 1/44.16 | |POLY-3 PERCENT (g) | 4.7% 2.2% 10.1% 6.2% |0.0% 0.0% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 1/36 (3%) 4/27 (15%) 2/41 (5%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 598 731 (T) 731 (T) 499 |--- --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.383 P=0.459N P=0.292 P=0.581 |P=0.192 (e) (e) P=0.483 | |POLY 3 | P=0.352 P=0.479N P=0.305 P=0.560 |P=0.195 (e) (e) P=0.492 | |POLY 1.5 | P=0.328 P=0.490N P=0.314 P=0.536 |P=0.197 (e) (e) P=0.494 | |POLY 6 | P=0.379 P=0.466N P=0.289 P=0.587 |P=0.194 (e) (e) P=0.490 | |LOGISTIC REGRESSION| P=0.280 P=0.509N P=0.321 P=0.228 |(e) (e) (e) P=0.483 | |COCH-ARM / FISHERS | P=0.292 P=0.500N P=0.339 P=0.500 |P=0.199 (e) (e) P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 3/50 (6%) 4/50 (8%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 4/42.86 2/45.17 3/40.06 4/48.66 |1/46.16 0/44.73 0/42.98 2/44.16 | |POLY-3 PERCENT (g) | 9.3% 4.4% 7.5% 8.2% |2.2% 0.0% 0.0% 4.5% | |TERMINAL (d) | 1/31 (3%) 2/36 (6%) 1/27 (4%) 2/41 (5%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 2/33 (6%) | |FIRST INCIDENCE | 598 731 (T) 677 499 |670 --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.557N P=0.278N P=0.545N P=0.519N |P=0.230 P=0.509N P=0.524N P=0.466 | |POLY 3 | P=0.535 P=0.313N P=0.537N P=0.572N |P=0.242 P=0.506N P=0.514N P=0.485 | |POLY 1.5 | P=0.514 P=0.326N P=0.527N P=0.601N |P=0.243 P=0.505N P=0.512N P=0.489 | |POLY 6 | P=0.561 P=0.299N P=0.553N P=0.538N |P=0.241 P=0.509N P=0.516N P=0.479 | |LOGISTIC REGRESSION| P=0.457 P=0.348N P=0.498N P=0.406 |P=0.240 P=0.482N P=0.482N P=0.490 | |COCH-ARM / FISHERS | P=0.481 P=0.339N P=0.500N P=0.643N |P=0.246 P=0.500N P=0.505N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 6/50 (12%) 2/50 (4%) |3/50 (6%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.43 3/45.72 6/40.67 2/48.27 |3/47.16 0/44.73 1/42.98 0/44.16 | |POLY-3 PERCENT (g) | 4.7% 6.6% 14.8% 4.1% |6.4% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/31 (0%) 1/36 (3%) 2/27 (7%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 577 593 609 633 |526 --- 734 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.481N P=0.563 P=0.119 P=0.605N |P=0.097N P=0.131N P=0.337N P=0.134N | |POLY 3 | P=0.515N P=0.534 P=0.118 P=0.646N |P=0.086N P=0.128N P=0.339N P=0.131N | |POLY 1.5 | P=0.548N P=0.517 P=0.121 P=0.666N |P=0.086N P=0.126N P=0.331N P=0.127N | |POLY 6 | P=0.475N P=0.554 P=0.113 P=0.622N |P=0.086N P=0.133N P=0.346N P=0.136N | |LOGISTIC REGRESSION| P=0.528 P=0.486 P=0.134 P=0.516 |P=0.073N P=0.067N P=0.225N P=0.059N | |COCH-ARM / FISHERS | P=0.558 P=0.500 P=0.134 P=0.691N |P=0.087N P=0.121N P=0.316N P=0.121N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) 5/50 (10%) 9/50 (18%) |5/50 (10%) 3/50 (6%) 6/49 (12%) 2/50 (4%) | |POLY-3 RATE (b) | 6/42.35 4/45.17 5/41.44 9/47.98 |5/46.55 3/44.73 6/43.89 2/44.70 | |POLY-3 PERCENT (g) | 14.2% 8.9% 12.1% 18.8% |10.7% 6.7% 13.7% 4.5% | |TERMINAL (d) | 3/31 (10%) 4/36 (11%) 1/27 (4%) 8/41 (20%) |4/36 (11%) 3/33 (9%) 2/35 (6%) 1/33 (3%) | |FIRST INCIDENCE | 637 731 (T) 535 698 |523 735 (T) 613 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.288 P=0.277N P=0.559N P=0.511 |P=0.272N P=0.400N P=0.470 P=0.247N | |POLY 3 | P=0.194 P=0.329N P=0.515N P=0.382 |P=0.257N P=0.378N P=0.459 P=0.233N | |POLY 1.5 | P=0.176 P=0.349N P=0.516N P=0.342 |P=0.253N P=0.373N P=0.463 P=0.229N | |POLY 6 | P=0.217 P=0.307N P=0.519N P=0.430 |P=0.260N P=0.387N P=0.464 P=0.237N | |LOGISTIC REGRESSION| P=0.173 P=0.310N P=0.494N P=0.412 |P=0.238N P=0.360N P=0.506 P=0.185N | |COCH-ARM / FISHERS | P=0.151 P=0.370N P=0.500N P=0.288 |P=0.242N P=0.357N P=0.486 P=0.218N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Oral Mucosa | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/13 (92%) 12/14 (86%) 10/12 (83%) 22/24 (92%) |9/11 (82%) 24/24 (100%) 17/18 (94%) 4/5 (80%) | |POLY-3 RATE (b) | 12/13.00 12/13.17 10/11.39 22/23.87 |9/11.00 24/24.00 17/17.64 4/4.74 | |POLY-3 PERCENT (g) | 92.3% 91.1% 87.8% 92.2% |81.8% 100.0% 96.4% 84.4% | |TERMINAL (d) | 10/11 (91%) 11/12 (92%) 8/9 (89%) 21/22 (96%) |8/10 (80%) 17/17 (100%) 14/14 (100%) 2/2 (100%) | |FIRST INCIDENCE | 429 725 488 666 |620 85 543 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.553N P=0.482N P=0.638N P=0.563N |P=0.498 P=0.007 ** P=0.076 P=0.358 | |POLY 3 | P=0.592 P=0.724N P=0.621N P=0.733N |P=0.619 P=0.077 P=0.250 P=0.717 | |POLY 1.5 | P=0.570 P=0.666N P=0.559N P=0.721N |P=0.698 P=0.077 P=0.284 P=0.742 | |POLY 6 | P=0.593 P=0.755N P=0.685N P=0.734 |P=0.457 P=0.077 P=0.202 P=0.669 | |LOGISTIC REGRESSION| P=0.546N P=0.518N P=0.495N P=0.724N |P=0.598N (e) P=0.287 P=0.755N | |COCH-ARM / FISHERS | P=0.511 P=0.529N P=0.469N P=0.740 |P=0.599N P=0.092 P=0.316 P=0.705N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/13 (31%) 9/14 (64%) 6/12 (50%) 12/24 (50%) |8/11 (73%) 8/24 (33%) 3/18 (17%) 1/5 (20%) | |POLY-3 RATE (b) | 4/11.90 9/13.98 6/10.69 12/23.76 |8/11.00 8/22.06 3/17.20 1/4.58 | |POLY-3 PERCENT (g) | 33.6% 64.4% 56.1% 50.5% |72.7% 36.3% 17.4% 21.8% | |TERMINAL (d) | 4/11 (36%) 8/12 (67%) 5/9 (56%) 11/22 (50%) |7/10 (70%) 5/17 (29%) 1/14 (7%) 0/2 (0%) | |FIRST INCIDENCE | 731 (T) 404 535 698 |620 561 632 723 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.422 P=0.093 P=0.220 P=0.263 |P=0.032N* P=0.264N P=0.037N* P=0.256N | |POLY 3 | P=0.458 P=0.119 P=0.258 P=0.279 |P=0.008N** P=0.045N* P=0.002N** P=0.087N | |POLY 1.5 | P=0.428 P=0.104 P=0.270 P=0.258 |P=0.008N** P=0.040N* P<0.001N** P=0.075N | |POLY 6 | P=0.483 P=0.134 P=0.248 P=0.299 |P=0.008N** P=0.052N P=0.002N** P=0.115N | |LOGISTIC REGRESSION| P=0.405 P=0.088 P=0.230 P=0.292 |P=0.013N* P=0.043N* P=0.003N** P=0.076N | |COCH-ARM / FISHERS | P=0.373 P=0.087 P=0.284 P=0.219 |P=0.013N* P=0.035N* P=0.004N** P=0.077N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 5/50 (10%) 4/49 (8%) 2/50 (4%) | |POLY-3 RATE (b) | |5/46.05 5/45.44 4/42.98 2/44.16 | |POLY-3 PERCENT (g) | |10.9% 11.0% 9.3% 4.5% | |TERMINAL (d) | |3/36 (8%) 3/33 (9%) 4/35 (11%) 2/33 (6%) | |FIRST INCIDENCE | |702 597 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.171N P=0.581 P=0.515N P=0.256N | |POLY 3 | |P=0.163N P=0.622 P=0.543N P=0.233N | |POLY 1.5 | |P=0.158N P=0.621 P=0.536N P=0.229N | |POLY 6 | |P=0.168N P=0.621 P=0.546N P=0.239N | |LOGISTIC REGRESSION| |P=0.161N P=0.622 P=0.534N P=0.241N | |COCH-ARM / FISHERS | |P=0.146N P=0.630N P=0.513N P=0.218N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.64 2/45.17 0/39.67 0/47.85 |0/45.91 0/44.73 1/42.98 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 4.4% 0.0% 0.0% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 1/31 (3%) 2/36 (6%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 1/35 (3%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) 731 (T) --- --- |--- --- 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.160N P=0.552 P=0.528N P=0.444N |P=0.686 (e) P=0.494 (e) | |POLY 3 | P=0.172N P=0.528 P=0.510N P=0.472N |P=0.682 (e) P=0.487 (e) | |POLY 1.5 | P=0.179N P=0.514 P=0.508N P=0.484N |P=0.685 (e) P=0.489 (e) | |POLY 6 | P=0.161N P=0.546 P=0.513N P=0.458N |P=0.677 (e) P=0.486 (e) | |LOGISTIC REGRESSION| P=0.160N P=0.552 (e) (e) |(e) (e) P=0.494 (e) | |COCH-ARM / FISHERS | P=0.188N P=0.500 P=0.500N P=0.500N |P=0.694 (e) P=0.495 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.64 1/45.17 0/39.67 1/47.85 |0/45.91 0/44.73 2/43.11 1/44.16 | |POLY-3 PERCENT (g) | 2.4% 2.2% 0.0% 2.1% |0.0% 0.0% 4.6% 2.3% | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 0/27 (0%) 1/41 (2%) |0/36 (0%) 0/33 (0%) 1/35 (3%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) 731 (T) --- 731 (T) |--- --- 702 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.553N P=0.728N P=0.528N P=0.698N |P=0.236 (e) P=0.237 P=0.483 | |POLY 3 | P=0.608N P=0.742N P=0.510N P=0.729N |P=0.234 (e) P=0.223 P=0.492 | |POLY 1.5 | P=0.613N P=0.752N P=0.508N P=0.742N |P=0.238 (e) P=0.225 P=0.494 | |POLY 6 | P=0.602N P=0.730N P=0.513N P=0.711N |P=0.230 (e) P=0.223 P=0.490 | |LOGISTIC REGRESSION| P=0.553N P=0.728N (e) P=0.698N |P=0.236 (e) P=0.224 P=0.483 | |COCH-ARM / FISHERS | P=0.616N P=0.753N P=0.500N P=0.753N |P=0.246 (e) P=0.242 P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 20/50 (40%) 23/50 (46%) 16/50 (32%) |14/50 (28%) 14/50 (28%) 5/49 (10%) 11/50 (22%) | |POLY-3 RATE (b) | 25/45.12 20/45.75 23/42.51 16/47.94 |14/46.46 14/45.98 5/42.98 11/46.07 | |POLY-3 PERCENT (g) | 55.4% 43.7% 54.1% 33.4% |30.1% 30.5% 11.6% 23.9% | |TERMINAL (d) | 16/31 (52%) 17/36 (47%) 15/27 (56%) 15/41 (37%) |12/36 (33%) 10/33 (30%) 5/35 (14%) 5/33 (15%) | |FIRST INCIDENCE | 499 648 506 709 |652 597 735 (T) 568 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010N* P=0.089N P=0.528 P=0.006N** |P=0.236N P=0.499 P=0.024N* P=0.414N | |POLY 3 | P=0.028N* P=0.178N P=0.538N P=0.024N* |P=0.184N P=0.577 P=0.028N* P=0.329N | |POLY 1.5 | P=0.038N* P=0.198N P=0.508N P=0.032N* |P=0.185N P=0.573 P=0.026N* P=0.333N | |POLY 6 | P=0.019N* P=0.158N P=0.578N P=0.017N* |P=0.179N P=0.577 P=0.029N* P=0.320N | |LOGISTIC REGRESSION| P=0.025N* P=0.143N P=0.492N P=0.026N* |P=0.196N P=0.560 P=0.028N* P=0.332N | |COCH-ARM / FISHERS | P=0.061N P=0.211N P=0.421N P=0.052N |P=0.180N P=0.588N P=0.022N* P=0.322N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Acinus | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/41.64 2/45.17 1/39.85 0/47.85 |1/45.91 1/44.88 0/42.98 1/44.16 | |POLY-3 PERCENT (g) | 0.0% 4.4% 2.5% 0.0% |2.2% 2.2% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 2/36 (6%) 0/27 (0%) 0/41 (0%) |1/36 (3%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | --- 731 (T) 682 --- |735 (T) 697 --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.403N P=0.272 P=0.481 (e) |P=0.628N P=0.751 P=0.506N P=0.742 | |POLY 3 | P=0.410N P=0.256 P=0.491 (e) |P=0.621N P=0.756 P=0.513N P=0.752 | |POLY 1.5 | P=0.432N P=0.246 P=0.493 (e) |P=0.619N P=0.756 P=0.511N P=0.754 | |POLY 6 | P=0.382N P=0.268 P=0.489 (e) |P=0.621N P=0.754 P=0.514N P=0.749 | |LOGISTIC REGRESSION| P=0.425N P=0.272 P=0.495 (e) |P=0.627N P=0.758 (e) P=0.742 | |COCH-ARM / FISHERS | P=0.461N P=0.247 P=0.500 (e) |P=0.616N P=0.753N P=0.505N P=0.753N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 7/50 (14%) 3/50 (6%) 10/50 (20%) |8/50 (16%) 4/50 (8%) 4/49 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 3/42.07 7/45.36 3/40.32 10/47.85 |8/46.61 4/44.96 4/42.98 1/44.49 | |POLY-3 PERCENT (g) | 7.1% 15.4% 7.4% 20.9% |17.2% 8.9% 9.3% 2.3% | |TERMINAL (d) | 2/31 (7%) 6/36 (17%) 1/27 (4%) 10/41 (24%) |6/36 (17%) 3/33 (9%) 4/35 (11%) 0/33 (0%) | |FIRST INCIDENCE | 606 682 593 731 (T) |620 675 735 (T) 643 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.102 P=0.229 P=0.617 P=0.100 |P=0.020N* P=0.219N P=0.200N P=0.027N* | |POLY 3 | P=0.056 P=0.189 P=0.643 P=0.059 |P=0.016N* P=0.194N P=0.218N P=0.019N* | |POLY 1.5 | P=0.047 * P=0.173 P=0.646 P=0.048 * |P=0.015N* P=0.190N P=0.210N P=0.018N* | |POLY 6 | P=0.068 P=0.210 P=0.638 P=0.075 |P=0.016N* P=0.202N P=0.224N P=0.020N* | |LOGISTIC REGRESSION| P=0.071 P=0.201 P=0.655 P=0.081 |P=0.016N* P=0.186N P=0.208N P=0.017N* | |COCH-ARM / FISHERS | P=0.039 * P=0.159 P=0.661N P=0.036 * |P=0.015N* P=0.178N P=0.188N P=0.015N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 3/50 (6%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.09 0/45.17 0/39.67 1/47.85 |2/45.91 3/44.97 1/43.67 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 2.1% |4.4% 6.7% 2.3% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 1/41 (2%) |2/36 (6%) 2/33 (6%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 598 --- --- 731 (T) |735 (T) 671 498 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.627 P=0.482N P=0.510N P=0.712N |P=0.116N P=0.466 P=0.516N P=0.258N | |POLY 3 | P=0.604 P=0.486N P=0.512N P=0.731N |P=0.111N P=0.491 P=0.517N P=0.246N | |POLY 1.5 | P=0.601 P=0.493N P=0.509N P=0.744N |P=0.109N P=0.492 P=0.516N P=0.244N | |POLY 6 | P=0.608 P=0.477N P=0.517N P=0.716N |P=0.113N P=0.488 P=0.516N P=0.249N | |LOGISTIC REGRESSION| P=0.583 P=0.490N P=0.462N P=0.708 |P=0.099N P=0.484 P=0.449N (e) | |COCH-ARM / FISHERS | P=0.595 P=0.500N P=0.500N P=0.753N |P=0.104N P=0.500 P=0.508N P=0.247N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 6/50 (12%) 3/50 (6%) 4/50 (8%) |27/50 (54%) 27/50 (54%) 19/49 (39%) 22/50 (44%) | |POLY-3 RATE (b) | 4/42.82 6/45.69 3/39.67 4/48.07 |27/48.21 27/46.16 19/44.69 22/45.58 | |POLY-3 PERCENT (g) | 9.3% 13.1% 7.6% 8.3% |56.0% 58.5% 42.5% 48.3% | |TERMINAL (d) | 2/31 (7%) 4/36 (11%) 3/27 (11%) 3/41 (7%) |19/36 (53%) 20/33 (61%) 15/35 (43%) 16/33 (49%) | |FIRST INCIDENCE | 505 648 731 (T) 672 |526 620 177 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.323N P=0.464 P=0.558N P=0.511N |P=0.213N P=0.432 P=0.132N P=0.355N | |POLY 3 | P=0.391N P=0.411 P=0.542N P=0.578N |P=0.166N P=0.485 P=0.134N P=0.292N | |POLY 1.5 | P=0.417N P=0.389 P=0.530N P=0.606N |P=0.149N P=0.512 P=0.117N P=0.264N | |POLY 6 | P=0.360N P=0.440 P=0.560N P=0.543N |P=0.191N P=0.444 P=0.155N P=0.332N | |LOGISTIC REGRESSION| P=0.425N P=0.359 P=0.508N P=0.530 |P=0.146N P=0.536 P=0.099N P=0.249N | |COCH-ARM / FISHERS | P=0.449N P=0.370 P=0.500N P=0.643N |P=0.123N P=0.579N P=0.094N P=0.212N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 16/50 (32%) 18/50 (36%) 21/50 (42%) |19/50 (38%) 21/50 (42%) 23/49 (47%) 21/50 (42%) | |POLY-3 RATE (b) | 13/43.99 16/46.34 18/41.34 21/48.33 |19/46.53 21/46.42 23/43.55 21/44.93 | |POLY-3 PERCENT (g) | 29.6% 34.5% 43.6% 43.5% |40.8% 45.2% 52.8% 46.7% | |TERMINAL (d) | 8/31 (26%) 12/36 (33%) 14/27 (52%) 19/41 (46%) |17/36 (47%) 15/33 (46%) 21/35 (60%) 17/33 (52%) | |FIRST INCIDENCE | 499 593 577 633 |597 618 632 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.238 P=0.513 P=0.119 P=0.301 |P=0.283 P=0.311 P=0.216 P=0.291 | |POLY 3 | P=0.086 P=0.389 P=0.127 P=0.119 |P=0.303 P=0.413 P=0.173 P=0.359 | |POLY 1.5 | P=0.071 P=0.355 P=0.144 P=0.095 |P=0.328 P=0.404 P=0.190 P=0.375 | |POLY 6 | P=0.109 P=0.436 P=0.107 P=0.155 |P=0.278 P=0.425 P=0.166 P=0.341 | |LOGISTIC REGRESSION| P=0.096 P=0.348 P=0.158 P=0.095 |P=0.300 P=0.377 P=0.171 P=0.328 | |COCH-ARM / FISHERS | P=0.053 P=0.330 P=0.194 P=0.069 |P=0.382 P=0.419 P=0.243 P=0.419 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/41.64 0/45.17 2/40.13 0/47.85 |0/45.91 0/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 4.8% 0.0% 5.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/31 (7%) 0/36 (0%) 1/27 (4%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) --- 593 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.210N P=0.206N P=0.654 P=0.179N |(e) (e) (e) (e) | |POLY 3 | P=0.229N P=0.219N P=0.681 P=0.208N |(e) (e) (e) (e) | |POLY 1.5 | P=0.235N P=0.228N P=0.683 P=0.220N |(e) (e) (e) (e) | |POLY 6 | P=0.222N P=0.209N P=0.678 P=0.194N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.239N (e) P=0.680 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.248N P=0.247N P=0.691N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/49 (4%) 2/50 (4%) 3/50 (6%) | | |POLY-3 RATE (b) | 0/41.64 2/44.35 2/39.67 3/47.85 | | |POLY-3 PERCENT (g) | 0.0% 4.5% 5.0% 6.3% | | |TERMINAL (d) | 0/31 (0%) 1/36 (3%) 2/27 (7%) 3/41 (7%) | | |FIRST INCIDENCE | --- 725 731 (T) 731 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.170 P=0.276 P=0.208 P=0.175 | | |POLY 3 | P=0.145 P=0.251 P=0.226 P=0.146 | | |POLY 1.5 | P=0.130 P=0.242 P=0.229 P=0.134 | | |POLY 6 | P=0.165 P=0.264 P=0.222 P=0.161 | | |LOGISTIC REGRESSION| P=0.167 P=0.272 P=0.208 P=0.175 | | |COCH-ARM / FISHERS | P=0.110 P=0.242 P=0.247 P=0.121 | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/50 (86%) 47/49 (96%) 43/50 (86%) 49/50 (98%) | | |POLY-3 RATE (b) | 43/46.74 47/47.18 43/46.27 49/50.00 | | |POLY-3 PERCENT (g) | 92.0% 99.6% 92.9% 98.0% | | |TERMINAL (d) | 30/31 (97%) 36/36 (100%) 27/27 (100%) 40/41 (98%) | | |FIRST INCIDENCE | 505 591 488 499 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.157N P=0.364N P=0.259 P=0.146N | | |POLY 3 | P=0.208 P=0.046 * P=0.603 P=0.149 | | |POLY 1.5 | P=0.111 P=0.037 * P=0.543 P=0.071 | | |POLY 6 | P=0.411 P=0.114 P=0.694 P=0.349 | | |LOGISTIC REGRESSION| P=0.227 P=0.157 P=0.444 P=0.227 | | |COCH-ARM / FISHERS | P=0.066 P=0.085 P=0.613N P=0.030 * | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland: Duct | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 7/49 (14%) 6/50 (12%) 9/50 (18%) | | |POLY-3 RATE (b) | 7/42.98 7/44.67 6/41.02 9/48.47 | | |POLY-3 PERCENT (g) | 16.3% 15.7% 14.6% 18.6% | | |TERMINAL (d) | 4/31 (13%) 5/36 (14%) 3/27 (11%) 6/41 (15%) | | |FIRST INCIDENCE | 577 643 535 666 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.516 P=0.496N P=0.566N P=0.589N | | |POLY 3 | P=0.415 P=0.584N P=0.536N P=0.496 | | |POLY 1.5 | P=0.382 P=0.607N P=0.529N P=0.453 | | |POLY 6 | P=0.459 P=0.554N P=0.549N P=0.549 | | |LOGISTIC REGRESSION| P=0.356 P=0.612N P=0.502N P=0.366 | | |COCH-ARM / FISHERS | P=0.335 P=0.597 P=0.500N P=0.393 | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Prostate | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/49 (2%) 1/49 (2%) 1/50 (2%) | | |POLY-3 RATE (b) | 3/42.58 1/44.33 1/38.67 1/47.85 | | |POLY-3 PERCENT (g) | 7.1% 2.3% 2.6% 2.1% | | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 1/26 (4%) 1/41 (2%) | | |FIRST INCIDENCE | 508 731 (T) 731 (T) 731 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.196N P=0.260N P=0.344N P=0.229N | | |POLY 3 | P=0.231N P=0.291N P=0.340N P=0.265N | | |POLY 1.5 | P=0.236N P=0.302N P=0.332N P=0.282N | | |POLY 6 | P=0.225N P=0.277N P=0.353N P=0.246N | | |LOGISTIC REGRESSION| P=0.245N P=0.322N P=0.302N P=0.441N | | |COCH-ARM / FISHERS | P=0.241N P=0.316N P=0.316N P=0.309N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 20/49 (41%) 20/49 (41%) 15/50 (30%) | | |POLY-3 RATE (b) | 23/46.81 20/45.96 20/42.54 15/49.13 | | |POLY-3 PERCENT (g) | 49.1% 43.5% 47.0% 30.5% | | |TERMINAL (d) | 13/31 (42%) 16/36 (44%) 10/26 (39%) 11/41 (27%) | | |FIRST INCIDENCE | 499 404 488 499 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020N* P=0.192N P=0.529N P=0.018N* | | |POLY 3 | P=0.037N* P=0.369N P=0.505N P=0.047N* | | |POLY 1.5 | P=0.045N* P=0.379N P=0.469N P=0.056N | | |POLY 6 | P=0.028N* P=0.359N P=0.548N P=0.037N* | | |LOGISTIC REGRESSION| P=0.070N P=0.403N P=0.369N P=0.230N | | |COCH-ARM / FISHERS | P=0.062N P=0.376N P=0.376N P=0.074N | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Prostate: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/49 (2%) 8/49 (16%) 6/50 (12%) | | |POLY-3 RATE (b) | 4/42.20 1/44.33 8/40.05 6/47.85 | | |POLY-3 PERCENT (g) | 9.5% 2.3% 20.0% 12.5% | | |TERMINAL (d) | 3/31 (10%) 1/36 (3%) 4/26 (15%) 6/41 (15%) | | |FIRST INCIDENCE | 554 731 (T) 577 731 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.241 P=0.145N P=0.133 P=0.538 | | |POLY 3 | P=0.183 P=0.164N P=0.149 P=0.451 | | |POLY 1.5 | P=0.164 P=0.175N P=0.151 P=0.417 | | |POLY 6 | P=0.207 P=0.150N P=0.146 P=0.493 | | |LOGISTIC REGRESSION| P=0.160 P=0.177N P=0.154 P=0.458 | | |COCH-ARM / FISHERS | P=0.138 P=0.187N P=0.168 P=0.370 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 7/50 (14%) 6/50 (12%) 1/50 (2%) |19/50 (38%) 8/49 (16%) 5/49 (10%) 11/50 (22%) | |POLY-3 RATE (b) | 5/41.64 7/45.55 6/40.13 1/47.85 |19/46.66 8/44.51 5/43.41 11/45.63 | |POLY-3 PERCENT (g) | 12.0% 15.4% 15.0% 2.1% |40.7% 18.0% 11.5% 24.1% | |TERMINAL (d) | 5/31 (16%) 5/36 (14%) 5/27 (19%) 1/41 (2%) |16/36 (44%) 7/33 (21%) 4/35 (11%) 6/33 (18%) | |FIRST INCIDENCE | 731 (T) 672 593 731 (T) |597 675 610 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033N* P=0.495 P=0.409 P=0.051N |P=0.109N P=0.022N* P=0.002N** P=0.112N | |POLY 3 | P=0.037N* P=0.443 P=0.474 P=0.073N |P=0.072N P=0.013N* P<0.001N** P=0.066N | |POLY 1.5 | P=0.047N* P=0.411 P=0.477 P=0.084N |P=0.073N P=0.014N* P<0.001N** P=0.067N | |POLY 6 | P=0.027N* P=0.486 P=0.467 P=0.061N |P=0.069N P=0.014N* P<0.001N** P=0.064N | |LOGISTIC REGRESSION| P=0.038N* P=0.491 P=0.442 P=0.051N |P=0.089N P=0.015N* P=0.002N** P=0.075N | |COCH-ARM / FISHERS | P=0.066N P=0.380 P=0.500 P=0.102N |P=0.076N P=0.014N* P<0.001N** P=0.063N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 19/50 (38%) 10/50 (20%) 18/50 (36%) 24/50 (48%) |7/50 (14%) 6/49 (12%) 6/49 (12%) 3/50 (6%) | |POLY-3 RATE (b) | 19/42.07 10/45.17 18/40.19 24/47.85 |7/45.91 6/44.29 6/42.98 3/44.30 | |POLY-3 PERCENT (g) | 45.2% 22.1% 44.8% 50.2% |15.3% 13.6% 14.0% 6.8% | |TERMINAL (d) | 18/31 (58%) 10/36 (28%) 16/27 (59%) 24/41 (59%) |7/36 (19%) 6/33 (18%) 6/35 (17%) 2/33 (6%) | |FIRST INCIDENCE | 606 731 (T) 645 731 (T) |735 (T) 735 (T) 735 (T) 697 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.213 P=0.008N** P=0.462 P=0.507N |P=0.146N P=0.569N P=0.522N P=0.193N | |POLY 3 | P=0.076 P=0.017N* P=0.577N P=0.396 |P=0.138N P=0.528N P=0.551N P=0.172N | |POLY 1.5 | P=0.061 P=0.025N* P=0.560N P=0.309 |P=0.135N P=0.527N P=0.543N P=0.169N | |POLY 6 | P=0.100 P=0.010N* P=0.587 P=0.513 |P=0.141N P=0.532N P=0.553N P=0.175N | |LOGISTIC REGRESSION| P=0.209 P=0.007N** P=0.528 P=0.494N |P=0.141N P=0.569N P=0.522N P=0.183N | |COCH-ARM / FISHERS | P=0.047 * P=0.038N* P=0.500N P=0.210 |P=0.125N P=0.516N P=0.516N P=0.159N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Salivary Glands | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 2/49 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.15 0/45.17 0/39.67 1/47.85 |1/45.91 2/44.82 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 2.1% |2.2% 4.5% 0.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 1/41 (2%) |1/36 (3%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 577 --- --- 731 (T) |735 (T) 597 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.621 P=0.487N P=0.509N P=0.720N |P=0.199N P=0.484 P=0.506N P=0.517N | |POLY 3 | P=0.604 P=0.486N P=0.512N P=0.731N |P=0.195N P=0.492 P=0.513N P=0.508N | |POLY 1.5 | P=0.601 P=0.493N P=0.509N P=0.744N |P=0.193N P=0.490 P=0.511N P=0.506N | |POLY 6 | P=0.608 P=0.478N P=0.517N P=0.716N |P=0.196N P=0.493 P=0.514N P=0.510N | |LOGISTIC REGRESSION| P=0.578 P=0.480N P=0.448N P=0.687 |P=0.182N P=0.510 (e) (e) | |COCH-ARM / FISHERS | P=0.595 P=0.500N P=0.500N P=0.753N |P=0.188N P=0.492 P=0.505N P=0.500N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/41.64 2/45.17 0/39.67 0/47.85 |0/45.91 0/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 0.0% 4.4% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 2/36 (6%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 731 (T) --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.363N P=0.272 (e) (e) |(e) (e) (e) (e) | |POLY 3 | P=0.370N P=0.256 (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.387N P=0.246 (e) (e) |(e) (e) (e) (e) | |POLY 6 | P=0.348N P=0.268 (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.272 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/41.64 3/45.25 0/39.67 0/47.85 |0/45.91 0/44.73 0/42.98 0/44.16 | |POLY-3 PERCENT (g) | 0.0% 6.6% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 2/36 (6%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 710 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.269N P=0.152 (e) (e) |(e) (e) (e) (e) | |POLY 3 | P=0.266N P=0.134 (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.286N P=0.126 (e) (e) |(e) (e) (e) (e) | |POLY 6 | P=0.241N P=0.145 (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.271N P=0.149 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.311N P=0.121 (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 10/50 (20%) 4/50 (8%) 6/50 (12%) |5/50 (10%) 8/49 (16%) 3/49 (6%) 6/50 (12%) | |POLY-3 RATE (b) | 5/42.66 10/46.44 4/40.17 6/48.53 |5/46.09 8/46.16 3/42.98 6/44.88 | |POLY-3 PERCENT (g) | 11.7% 21.5% 10.0% 12.4% |10.9% 17.3% 7.0% 13.4% | |TERMINAL (d) | 2/31 (7%) 6/36 (17%) 3/27 (11%) 5/41 (12%) |4/36 (11%) 2/33 (6%) 3/35 (9%) 2/33 (6%) | |FIRST INCIDENCE | 499 404 577 499 |690 620 735 (T) 634 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.315N P=0.219 P=0.570N P=0.592N |P=0.546 P=0.250 P=0.375N P=0.451 | |POLY 3 | P=0.369N P=0.170 P=0.538N P=0.589 |P=0.554N P=0.276 P=0.395N P=0.481 | |POLY 1.5 | P=0.407N P=0.150 P=0.528N P=0.553 |P=0.547N P=0.271 P=0.389N P=0.485 | |POLY 6 | P=0.326N P=0.197 P=0.553N P=0.619N |P=0.558N P=0.283 P=0.398N P=0.479 | |LOGISTIC REGRESSION| P=0.465N P=0.124 P=0.511N P=0.378 |P=0.536N P=0.261 P=0.389N P=0.481 | |COCH-ARM / FISHERS | P=0.456N P=0.131 P=0.500N P=0.500 |P=0.527N P=0.264 P=0.369N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 5/50 (10%) |1/50 (2%) 0/49 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/41.64 2/45.17 1/39.67 5/47.85 |1/45.91 0/44.73 0/42.98 1/44.16 | |POLY-3 PERCENT (g) | 4.8% 4.4% 2.5% 10.5% |2.2% 0.0% 0.0% 2.3% | |TERMINAL (d) | 2/31 (7%) 2/36 (6%) 1/27 (4%) 5/41 (12%) |1/36 (3%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 731 (T) |735 (T) --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.187 P=0.641N P=0.549N P=0.341 |P=0.582 P=0.517N P=0.506N P=0.742 | |POLY 3 | P=0.134 P=0.665N P=0.517N P=0.277 |P=0.589 P=0.505N P=0.513N P=0.752 | |POLY 1.5 | P=0.125 P=0.679N P=0.513N P=0.251 |P=0.590 P=0.504N P=0.511N P=0.754 | |POLY 6 | P=0.147 P=0.646N P=0.523N P=0.311 |P=0.588 P=0.507N P=0.514N P=0.749 | |LOGISTIC REGRESSION| P=0.187 P=0.641N P=0.549N P=0.341 |P=0.582 (e) (e) P=0.742 | |COCH-ARM / FISHERS | P=0.114 P=0.691N P=0.500N P=0.218 |P=0.595 P=0.505N P=0.505N P=0.753N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/49 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/42.44 0/45.17 0/39.67 0/47.85 |1/45.91 0/44.73 0/42.98 2/45.50 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 0.0% |2.2% 0.0% 0.0% 4.4% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |1/36 (3%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 429 --- --- --- |735 (T) --- --- 172 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.306N P=0.508N P=0.508N P=0.500N |P=0.240 P=0.517N P=0.506N P=0.485 | |POLY 3 | P=0.325N P=0.488N P=0.513N P=0.476N |P=0.245 P=0.505N P=0.513N P=0.497 | |POLY 1.5 | P=0.318N P=0.494N P=0.510N P=0.486N |P=0.246 P=0.504N P=0.511N P=0.498 | |POLY 6 | P=0.334N P=0.479N P=0.518N P=0.463N |P=0.246 P=0.507N P=0.514N P=0.495 | |LOGISTIC REGRESSION| P=0.291N P=0.360N P=0.316N (e) |P=0.407 (e) (e) P=0.742 | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.247 P=0.505N P=0.505N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 3/42.48 1/45.36 1/39.87 0/47.85 |0/45.91 0/44.73 2/44.16 1/44.16 | |POLY-3 PERCENT (g) | 7.1% 2.2% 2.5% 0.0% |0.0% 0.0% 4.5% 2.3% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 554 682 677 --- |--- --- 459 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.059N P=0.254N P=0.333N P=0.086N |P=0.236 (e) P=0.228 P=0.483 | |POLY 3 | P=0.068N P=0.282N P=0.328N P=0.099N |P=0.233 (e) P=0.229 P=0.492 | |POLY 1.5 | P=0.070N P=0.294N P=0.322N P=0.107N |P=0.237 (e) P=0.228 P=0.494 | |POLY 6 | P=0.066N P=0.268N P=0.337N P=0.090N |P=0.229 (e) P=0.231 P=0.490 | |LOGISTIC REGRESSION| P=0.076N P=0.315N P=0.293N P=0.189N |P=0.268 (e) P=0.372 P=0.483 | |COCH-ARM / FISHERS | P=0.073N P=0.309N P=0.309N P=0.121N |P=0.246 (e) P=0.242 P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.64 2/45.36 3/40.44 0/47.85 |0/45.91 2/45.34 1/43.73 1/44.19 | |POLY-3 PERCENT (g) | 2.4% 4.4% 7.4% 0.0% |0.0% 4.4% 2.3% 2.3% | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 1/27 (4%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) 682 583 --- |--- 626 459 726 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.274N P=0.560 P=0.281 P=0.444N |P=0.484 P=0.232 P=0.492 P=0.483 | |POLY 3 | P=0.279N P=0.530 P=0.294 P=0.472N |P=0.481 P=0.234 P=0.490 P=0.492 | |POLY 1.5 | P=0.302N P=0.515 P=0.295 P=0.484N |P=0.486 P=0.234 P=0.491 P=0.494 | |POLY 6 | P=0.252N P=0.549 P=0.293 P=0.458N |P=0.476 P=0.234 P=0.491 P=0.490 | |LOGISTIC REGRESSION| P=0.338N P=0.539 P=0.300 (e) |P=0.535 P=0.262 P=0.731 P=0.489 | |COCH-ARM / FISHERS | P=0.337N P=0.500 P=0.309 P=0.500N |P=0.500 P=0.247 P=0.495 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 3/50 (6%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 3/42.48 3/45.54 3/40.44 1/47.85 |0/45.91 2/45.34 2/44.16 0/44.16 | |POLY-3 PERCENT (g) | 7.1% 6.6% 7.4% 2.1% |0.0% 4.4% 4.5% 0.0% | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 1/27 (4%) 1/41 (2%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 554 682 583 731 (T) |--- 626 459 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.165N P=0.581N P=0.630 P=0.227N |P=0.517N P=0.232 P=0.228 (e) | |POLY 3 | P=0.186N P=0.630N P=0.640 P=0.264N |P=0.519N P=0.234 P=0.229 (e) | |POLY 1.5 | P=0.200N P=0.647N P=0.644 P=0.281N |P=0.514N P=0.234 P=0.228 (e) | |POLY 6 | P=0.170N P=0.609N P=0.633 P=0.245N |P=0.524N P=0.234 P=0.231 (e) | |LOGISTIC REGRESSION| P=0.234N P=0.652 P=0.648N P=0.400N |P=0.453N P=0.262 P=0.372 (e) | |COCH-ARM / FISHERS | P=0.221N P=0.661N P=0.661N P=0.309N |P=0.500N P=0.247 P=0.242 (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.48 1/45.36 0/39.67 0/47.85 |0/45.91 0/44.73 2/44.16 0/44.16 | |POLY-3 PERCENT (g) | 4.7% 2.2% 0.0% 0.0% |0.0% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 554 682 --- --- |--- --- 459 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.088N P=0.443N P=0.248N P=0.196N |P=0.585 (e) P=0.228 (e) | |POLY 3 | P=0.100N P=0.477N P=0.252N P=0.212N |P=0.577 (e) P=0.229 (e) | |POLY 1.5 | P=0.101N P=0.489N P=0.248N P=0.222N |P=0.583 (e) P=0.228 (e) | |POLY 6 | P=0.100N P=0.463N P=0.260N P=0.200N |P=0.570 (e) P=0.231 (e) | |LOGISTIC REGRESSION| P=0.104N P=0.505N P=0.195N P=0.420N |P=0.646 (e) P=0.372 (e) | |COCH-ARM / FISHERS | P=0.101N P=0.500N P=0.247N P=0.247N |P=0.594 (e) P=0.242 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/41.92 2/45.47 0/39.67 1/48.20 |0/45.91 0/44.73 2/43.74 0/44.16 | |POLY-3 PERCENT (g) | 4.8% 4.4% 0.0% 2.1% |0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 655 648 --- 633 |--- --- 459 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.239N P=0.623N P=0.258N P=0.397N |P=0.584 (e) P=0.232 (e) | |POLY 3 | P=0.281N P=0.664N P=0.249N P=0.452N |P=0.578 (e) P=0.226 (e) | |POLY 1.5 | P=0.289N P=0.679N P=0.246N P=0.472N |P=0.583 (e) P=0.227 (e) | |POLY 6 | P=0.271N P=0.646N P=0.255N P=0.427N |P=0.572 (e) P=0.227 (e) | |LOGISTIC REGRESSION| P=0.302N P=0.693N P=0.246N P=0.586N |P=0.627 (e) P=0.309 (e) | |COCH-ARM / FISHERS | P=0.296N P=0.691N P=0.247N P=0.500N |P=0.594 (e) P=0.242 (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular: Epithelium | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 4/42.92 2/45.94 0/39.67 1/48.06 |0/45.91 0/44.73 0/42.98 1/44.16 | |POLY-3 PERCENT (g) | 9.3% 4.4% 0.0% 2.1% |0.0% 0.0% 0.0% 2.3% | |TERMINAL (d) | 0/31 (0%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 554 593 --- 675 |--- --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.068N P=0.273N P=0.078N P=0.118N |P=0.192 (e) (e) P=0.483 | |POLY 3 | P=0.083N P=0.306N P=0.070N P=0.147N |P=0.195 (e) (e) P=0.492 | |POLY 1.5 | P=0.084N P=0.322N P=0.067N P=0.159N |P=0.197 (e) (e) P=0.494 | |POLY 6 | P=0.081N P=0.288N P=0.076N P=0.133N |P=0.194 (e) (e) P=0.490 | |LOGISTIC REGRESSION| P=0.096N P=0.348N P=0.052N P=0.328N |(e) (e) (e) P=0.483 | |COCH-ARM / FISHERS | P=0.086N P=0.339N P=0.059N P=0.181N |P=0.199 (e) (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular: Epithelium | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.64 0/45.17 0/39.67 1/48.20 |0/45.91 0/44.73 2/43.74 0/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 2.1% |0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 0/27 (0%) 0/41 (0%) |0/36 (0%) 0/33 (0%) 0/35 (0%) 0/33 (0%) | |FIRST INCIDENCE | 731 (T) --- --- 633 |--- --- 459 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.635 P=0.470N P=0.528N P=0.697N |P=0.584 (e) P=0.232 (e) | |POLY 3 | P=0.605 P=0.484N P=0.510N P=0.727N |P=0.578 (e) P=0.226 (e) | |POLY 1.5 | P=0.601 P=0.492N P=0.508N P=0.741N |P=0.583 (e) P=0.227 (e) | |POLY 6 | P=0.610 P=0.474N P=0.513N P=0.708N |P=0.572 (e) P=0.227 (e) | |LOGISTIC REGRESSION| P=0.592 (e) (e) P=0.742 |P=0.627 (e) P=0.309 (e) | |COCH-ARM / FISHERS | P=0.595 P=0.500N P=0.500N P=0.753N |P=0.594 (e) P=0.242 (e) | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular: Glands | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 34/50 (68%) 37/50 (74%) 27/50 (54%) 39/50 (78%) |36/50 (72%) 36/50 (72%) 39/49 (80%) 38/50 (76%) | |POLY-3 RATE (b) | 34/46.25 37/48.63 27/42.62 39/49.54 |36/47.98 36/46.05 39/45.93 38/47.32 | |POLY-3 PERCENT (g) | 73.5% 76.1% 63.4% 78.7% |75.0% 78.2% 84.9% 80.3% | |TERMINAL (d) | 23/31 (74%) 26/36 (72%) 20/27 (74%) 33/41 (81%) |28/36 (78%) 29/33 (88%) 31/35 (89%) 28/33 (85%) | |FIRST INCIDENCE | 499 404 506 499 |526 652 459 564 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.240N P=0.425N P=0.316N P=0.265N |P=0.191 P=0.356 P=0.256 P=0.231 | |POLY 3 | P=0.363 P=0.479 P=0.198N P=0.356 |P=0.273 P=0.452 P=0.164 P=0.351 | |POLY 1.5 | P=0.315 P=0.394 P=0.169N P=0.276 |P=0.272 P=0.491 P=0.182 P=0.355 | |POLY 6 | P=0.423 P=0.593 P=0.253N P=0.464 |P=0.289 P=0.387 P=0.159 P=0.351 | |LOGISTIC REGRESSION| P=0.424 P=0.378 P=0.150N P=0.312 |P=0.197 P=0.503 P=0.142 P=0.307 | |COCH-ARM / FISHERS | P=0.260 P=0.330 P=0.109N P=0.184 |P=0.312 P=0.588N P=0.259 P=0.410 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Testes | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 38/50 (76%) 44/49 (90%) 36/50 (72%) 41/50 (82%) | | |POLY-3 RATE (b) | 38/45.85 44/47.18 36/44.80 41/49.19 | | |POLY-3 PERCENT (g) | 82.9% 93.3% 80.4% 83.4% | | |TERMINAL (d) | 28/31 (90%) 33/36 (92%) 23/27 (85%) 34/41 (83%) | | |FIRST INCIDENCE | 499 591 506 633 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.067N P=0.565N P=0.427 P=0.095N | | |POLY 3 | P=0.348N P=0.090 P=0.483N P=0.589 | | |POLY 1.5 | P=0.455N P=0.055 P=0.492N P=0.463 | | |POLY 6 | P=0.233N P=0.192 P=0.470N P=0.488N | | |LOGISTIC REGRESSION| P=0.268N P=0.125 P=0.537N P=0.471N | | |COCH-ARM / FISHERS | P=0.493 P=0.059 P=0.410N P=0.312 | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 3/50 (6%) 2/50 (4%) | | |POLY-3 RATE (b) | 1/41.64 0/44.33 3/39.81 2/47.94 | | |POLY-3 PERCENT (g) | 2.4% 0.0% 7.5% 4.2% | | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 2/27 (7%) 1/41 (2%) | | |FIRST INCIDENCE | 731 (T) --- 695 709 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.325 P=0.470N P=0.259 P=0.598 | | |POLY 3 | P=0.290 P=0.488N P=0.288 P=0.549 | | |POLY 1.5 | P=0.272 P=0.496N P=0.292 P=0.528 | | |POLY 6 | P=0.312 P=0.477N P=0.283 P=0.574 | | |LOGISTIC REGRESSION| P=0.306 (e) P=0.270 P=0.585 | | |COCH-ARM / FISHERS | P=0.244 P=0.505N P=0.309 P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 4/49 (8%) 7/50 (14%) 3/50 (6%) | | |POLY-3 RATE (b) | 8/44.86 4/46.25 7/41.41 3/48.97 | | |POLY-3 PERCENT (g) | 17.8% 8.7% 16.9% 6.1% | | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 2/27 (7%) 0/41 (0%) | | |FIRST INCIDENCE | 499 404 506 499 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.093N P=0.147N P=0.559N P=0.070N | | |POLY 3 | P=0.099N P=0.162N P=0.567N P=0.074N | | |POLY 1.5 | P=0.108N P=0.175N P=0.548N P=0.084N | | |POLY 6 | P=0.089N P=0.147N P=0.592N P=0.063N | | |LOGISTIC REGRESSION| P=0.199N P=0.253N P=0.427N P=0.579N | | |COCH-ARM / FISHERS | P=0.124N P=0.188N P=0.500N P=0.100N | | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thymus | | Ectopic Parathyroid Gland | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/44 (5%) 1/45 (2%) 2/46 (4%) 2/43 (5%) |4/49 (8%) 3/47 (6%) 2/48 (4%) 6/47 (13%) | |POLY-3 RATE (b) | 2/36.92 1/41.45 2/36.34 2/42.00 |4/45.55 3/42.81 2/41.98 6/42.50 | |POLY-3 PERCENT (g) | 5.4% 2.4% 5.5% 4.8% |8.8% 7.0% 4.8% 14.1% | |TERMINAL (d) | 1/28 (4%) 1/35 (3%) 2/25 (8%) 2/37 (5%) |4/36 (11%) 1/32 (3%) 2/34 (6%) 4/31 (13%) | |FIRST INCIDENCE | 554 731 (T) 731 (T) 731 (T) |735 (T) 597 735 (T) 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.595 P=0.444N P=0.659 P=0.611N |P=0.206 P=0.550N P=0.363N P=0.297 | |POLY 3 | P=0.563 P=0.460N P=0.689 P=0.647N |P=0.221 P=0.534N P=0.375N P=0.326 | |POLY 1.5 | P=0.545 P=0.476N P=0.694 P=0.670N |P=0.224 P=0.533N P=0.368N P=0.330 | |POLY 6 | P=0.583 P=0.439N P=0.681 P=0.619N |P=0.218 P=0.535N P=0.379N P=0.323 | |LOGISTIC REGRESSION| P=0.550 P=0.504N P=0.691N P=0.645 |P=0.230 P=0.531N P=0.363N P=0.351 | |COCH-ARM / FISHERS | P=0.516 P=0.491N P=0.675N P=0.683 |P=0.233 P=0.524N P=0.349N P=0.344 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland | | Ultimobranchial Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 1/49 (2%) 2/49 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.64 0/45.17 2/40.27 2/47.85 |0/45.91 1/44.51 2/43.72 1/44.16 | |POLY-3 PERCENT (g) | 2.4% 0.0% 5.0% 4.2% |0.0% 2.3% 4.6% 2.3% | |TERMINAL (d) | 1/31 (3%) 0/36 (0%) 1/27 (4%) 2/41 (5%) |0/36 (0%) 0/33 (0%) 1/35 (3%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) --- 535 731 (T) |--- 675 470 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.309 P=0.470N P=0.468 P=0.597 |P=0.351 P=0.490 P=0.230 P=0.483 | |POLY 3 | P=0.281 P=0.484N P=0.488 P=0.548 |P=0.350 P=0.494 P=0.226 P=0.492 | |POLY 1.5 | P=0.267 P=0.492N P=0.490 P=0.528 |P=0.356 P=0.493 P=0.227 P=0.494 | |POLY 6 | P=0.297 P=0.474N P=0.485 P=0.573 |P=0.344 P=0.494 P=0.227 P=0.490 | |LOGISTIC REGRESSION| P=0.248 (e) P=0.502 P=0.597 |P=0.388 P=0.510 P=0.304 P=0.483 | |COCH-ARM / FISHERS | P=0.245 P=0.500N P=0.500 P=0.500 |P=0.368 P=0.495 P=0.242 P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 22/50 (44%) 20/50 (40%) 15/50 (30%) 23/50 (46%) |33/50 (66%) 23/49 (47%) 28/49 (57%) 21/50 (42%) | |POLY-3 RATE (b) | 22/44.11 20/46.43 15/40.85 23/48.66 |33/47.68 23/45.25 28/44.19 21/46.34 | |POLY-3 PERCENT (g) | 49.9% 43.1% 36.7% 47.3% |69.2% 50.8% 63.4% 45.3% | |TERMINAL (d) | 15/31 (48%) 14/36 (39%) 12/27 (44%) 19/41 (46%) |28/36 (78%) 18/33 (55%) 24/35 (69%) 14/33 (42%) | |FIRST INCIDENCE | 554 593 577 633 |526 620 613 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.265N P=0.219N P=0.216N P=0.224N |P=0.067N P=0.090N P=0.272N P=0.049N* | |POLY 3 | P=0.503N P=0.329N P=0.152N P=0.483N |P=0.026N* P=0.049N* P=0.352N P=0.013N* | |POLY 1.5 | P=0.532 P=0.376N P=0.137N P=0.556N |P=0.027N* P=0.050N P=0.323N P=0.014N* | |POLY 6 | P=0.446N P=0.276N P=0.183N P=0.399N |P=0.024N* P=0.050N P=0.360N P=0.012N* | |LOGISTIC REGRESSION| P=0.423N P=0.320N P=0.137N P=0.465N |P=0.041N* P=0.046N* P=0.346N P=0.018N* | |COCH-ARM / FISHERS | P=0.461 P=0.420N P=0.107N P=0.500 |P=0.028N* P=0.043N* P=0.242N P=0.013N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 3/50 (6%) |2/50 (4%) 0/49 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.07 2/45.36 2/40.33 3/47.85 |2/45.91 0/44.29 1/42.98 0/44.16 | |POLY-3 PERCENT (g) | 4.8% 4.4% 5.0% 6.3% |4.4% 0.0% 2.3% 0.0% | |TERMINAL (d) | 1/31 (3%) 1/36 (3%) 1/27 (4%) 3/41 (7%) |2/36 (6%) 0/33 (0%) 1/35 (3%) 0/33 (0%) | |FIRST INCIDENCE | 606 682 506 731 (T) |735 (T) --- 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.480 P=0.635N P=0.665 P=0.616 |P=0.199N P=0.258N P=0.510N P=0.258N | |POLY 3 | P=0.436 P=0.667N P=0.679 P=0.558 |P=0.192N P=0.245N P=0.523N P=0.246N | |POLY 1.5 | P=0.416 P=0.680N P=0.682 P=0.534 |P=0.190N P=0.245N P=0.520N P=0.244N | |POLY 6 | P=0.459 P=0.649N P=0.674 P=0.587 |P=0.192N P=0.246N P=0.524N P=0.249N | |LOGISTIC REGRESSION| P=0.383 P=0.696 P=0.678N P=0.532 |P=0.199N (e) P=0.510N (e) | |COCH-ARM / FISHERS | P=0.387 P=0.691N P=0.691N P=0.500 |P=0.188N P=0.253N P=0.508N P=0.247N | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 2/49 (4%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 3/41.64 0/45.17 0/39.67 2/47.85 |0/45.91 2/44.51 1/42.98 1/44.16 | |POLY-3 PERCENT (g) | 7.2% 0.0% 0.0% 4.2% |0.0% 4.5% 2.3% 2.3% | |TERMINAL (d) | 3/31 (10%) 0/36 (0%) 0/27 (0%) 2/41 (5%) |0/36 (0%) 1/33 (3%) 0/35 (0%) 1/33 (3%) | |FIRST INCIDENCE | 731 (T) --- --- 731 (T) |--- 675 734 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.453N P=0.096N P=0.145N P=0.373N |P=0.478 P=0.225 P=0.495 P=0.483 | |POLY 3 | P=0.546N P=0.105N P=0.127N P=0.437N |P=0.483 P=0.230 P=0.487 P=0.492 | |POLY 1.5 | P=0.540N P=0.112N P=0.125N P=0.463N |P=0.488 P=0.230 P=0.489 P=0.494 | |POLY 6 | P=0.552N P=0.096N P=0.130N P=0.405N |P=0.477 P=0.230 P=0.486 P=0.490 | |LOGISTIC REGRESSION| P=0.453N (e) (e) P=0.373N |P=0.489 P=0.233 P=0.493 P=0.483 | |COCH-ARM / FISHERS | P=0.531N P=0.121N P=0.121N P=0.500N |P=0.502 P=0.242 P=0.495 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 5/50 (10%) 5/49 (10%) 3/50 (6%) | |POLY-3 RATE (b) | |2/45.91 5/45.13 5/42.98 3/44.37 | |POLY-3 PERCENT (g) | |4.4% 11.1% 11.6% 6.8% | |TERMINAL (d) | |2/36 (6%) 4/33 (12%) 5/35 (14%) 1/33 (3%) | |FIRST INCIDENCE | |735 (T) 620 735 (T) 697 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.484 P=0.187 P=0.203 P=0.472 | |POLY 3 | |P=0.490 P=0.209 P=0.190 P=0.484 | |POLY 1.5 | |P=0.497 P=0.210 P=0.194 P=0.488 | |POLY 6 | |P=0.484 P=0.206 P=0.188 P=0.481 | |LOGISTIC REGRESSION| |P=0.490 P=0.206 P=0.203 P=0.476 | |COCH-ARM / FISHERS | |P=0.517 P=0.218 P=0.210 P=0.500 | |=================================================================================================================================| Date: 06/29/01 EXPERIMENT: 56111 TEST: 03 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - TRANS-CINNAMALDEHYDE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | VEHICLE .312% .625% 1.25% |VEHICLE .312% .625% 1.25% | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 2/50 (4%) 4/49 (8%) 4/50 (8%) | |POLY-3 RATE (b) | |5/45.91 2/45.04 4/42.98 4/44.16 | |POLY-3 PERCENT (g) | |10.9% 4.4% 9.3% 9.1% | |TERMINAL (d) | |5/36 (14%) 1/33 (3%) 3/35 (9%) 4/33 (12%) | |FIRST INCIDENCE | |735 (T) 652 734 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.551 P=0.250N P=0.518N P=0.555N | |POLY 3 | |P=0.568 P=0.224N P=0.541N P=0.524N | |POLY 1.5 | |P=0.568N P=0.224N P=0.535N P=0.518N | |POLY 6 | |P=0.562 P=0.225N P=0.543N P=0.532N | |LOGISTIC REGRESSION| |P=0.559 P=0.231N P=0.517N P=0.555N | |COCH-ARM / FISHERS | |P=0.556N P=0.218N P=0.513N P=0.500N | |=================================================================================================================================| (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).