TDMS Study 56348-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus CITRAL DATE: 07/06/01 EXPERIMENT: 56348 TEST: 04 TIME: 08:03:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: DR. M. RYAN CAS: 5392-40-5 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 UNTREAT CONTROL INCLUDE 002 UNTREAT CONTROL INCLUDE 005 500 PPM INCLUDE 006 500 PPM INCLUDE 007 1000 PPM INCLUDE 008 1000 PPM INCLUDE 009 2000 PPM INCLUDE 010 2000 PPM NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus CITRAL DATE: 07/06/01 EXPERIMENT: 56348 TEST: 04 TIME: 08:03:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-55384 ROUTE: DOSED FEED NTP C#: C56348 PATHOLOGIST: DR. M. RYAN CAS: 5392-40-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF CITRAL =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex: Subcapsular Hyperplasia Bone Marrow Hyperplasia Islets, Pancreatic Hyperplasia Kidney Nephropathy Kidney: Renal Tubule Mineralization Liver Angiectasis Clear Cell Focus Lung Hemorrhage Oral Mucosa Inflammation Chronic Ulcer Parathyroid Gland Cyst Pituitary Gland: Pars Distalis Hyperplasia Focal Spleen Hematopoietic Cell Proliferation Stomach, Forestomach Inflammation Thymus Atrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Kidney: Renal Tubule Mineralization Liver Infiltration Cellular Lymphocyte Inflammation Granulomatous Oral Mucosa Inflammation Chronic Ulcer Spleen: Lymphoid Follicle Atrophy Thymus Atrophy Hyperplasia Lymphoid Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 1/50 (2%) 5/50 (10%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 1/48.80 3/45.50 1/47.99 5/45.81 |1/43.96 0/47.89 2/47.49 2/45.29 | |POLY-3 PERCENT (g) | 2.1% 6.6% 2.1% 10.9% |2.3% 0.0% 4.2% 4.4% | |TERMINAL (d) | 1/48 (2%) 2/40 (5%) 1/42 (2%) 5/40 (13%) |1/40 (3%) 0/45 (0%) 2/43 (5%) 2/40 (5%) | |FIRST INCIDENCE | 727 (T) 626 727 (T) 727 (T) |733 (T) --- 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.057 P=0.251 P=0.732 P=0.067 |P=0.233 P=0.477N P=0.525 P=0.500 | |POLY 3 | P=0.068 P=0.281 P=0.757 P=0.088 |P=0.241 P=0.483N P=0.527 P=0.510 | |POLY 1.5 | P=0.072 P=0.291 P=0.758 P=0.094 |P=0.246 P=0.486N P=0.524 P=0.513 | |POLY 6 | P=0.064 P=0.271 P=0.753 P=0.081 |P=0.235 P=0.482N P=0.527 P=0.505 | |LOGISTIC REGRESSION| P=0.070 P=0.311 P=0.732 P=0.067 |P=0.233 (e) P=0.525 P=0.500 | |COCH-ARM / FISHERS | P=0.077 P=0.309 P=0.753N P=0.102 |P=0.246 P=0.500N P=0.500 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 17/50 (34%) 28/50 (56%) 22/50 (44%) |3/50 (6%) 2/50 (4%) 2/50 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 25/49.16 17/45.14 28/49.18 22/47.26 |3/43.96 2/47.89 2/47.49 3/45.75 | |POLY-3 PERCENT (g) | 50.9% 37.7% 56.9% 46.6% |6.8% 4.2% 4.2% 6.6% | |TERMINAL (d) | 24/48 (50%) 17/40 (43%) 26/42 (62%) 18/40 (45%) |3/40 (8%) 2/45 (4%) 2/43 (5%) 2/40 (5%) | |FIRST INCIDENCE | 626 727 (T) 427 456 |733 (T) 733 (T) 733 (T) 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.287 P=0.251N P=0.145 P=0.498 |P=0.531 P=0.446N P=0.467N P=0.658N | |POLY 3 | P=0.523 P=0.139N P=0.344 P=0.414N |P=0.547 P=0.461N P=0.465N P=0.644N | |POLY 1.5 | P=0.535 P=0.110N P=0.351 P=0.382N |P=0.551 P=0.467N P=0.469N P=0.643N | |POLY 6 | P=0.499 P=0.181N P=0.322 P=0.458N |P=0.542 P=0.458N P=0.465N P=0.648N | |LOGISTIC REGRESSION| P=0.479 P=0.179N P=0.341 P=0.399N |P=0.550 P=0.446N P=0.467N P=0.651N | |COCH-ARM / FISHERS | P=0.538N P=0.078N P=0.344 P=0.344N |P=0.544 P=0.500N P=0.500N P=0.661N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 36/50 (72%) 40/50 (80%) 47/50 (94%) 39/50 (78%) |47/50 (94%) 50/50 (100%) 49/50 (98%) 49/50 (98%) | |POLY-3 RATE (b) | 36/48.80 40/47.54 47/49.93 39/48.55 |47/47.48 50/50.00 49/49.68 49/50.00 | |POLY-3 PERCENT (g) | 73.8% 84.2% 94.1% 80.3% |99.0% 100.0% 98.6% 98.0% | |TERMINAL (d) | 36/48 (75%) 35/40 (88%) 40/42 (95%) 32/40 (80%) |40/40 (100%) 45/45 (100%) 43/43 (100%) 39/40 (98%) | |FIRST INCIDENCE | 727 (T) 419 427 447 |242 413 469 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.035 * P=0.013 * P<0.001 ** P=0.037 * |P=0.274 P=0.336N P=0.450N P=0.424 | |POLY 3 | P=0.251 P=0.153 P=0.005 ** P=0.297 |P=0.388N P=0.877 P=0.842N P=0.680N | |POLY 1.5 | P=0.254 P=0.186 P=0.004 ** P=0.310 |P=0.514N P=0.573 P=0.807 P=0.769N | |POLY 6 | P=0.240 P=0.121 P=0.005 ** P=0.277 |P=0.277N P=1.000 P=0.929N P=0.588N | |LOGISTIC REGRESSION| P=0.200 P=0.104 P=0.003 ** P=0.227 |P=0.590 P=0.581 P=0.703N P=0.611 | |COCH-ARM / FISHERS | P=0.252 P=0.241 P=0.003 ** P=0.322 |P=0.296 P=0.121 P=0.309 P=0.309 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 0/47.80 0/45.14 1/48.06 1/45.81 |1/43.96 0/47.89 2/47.49 2/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.1% 2.2% |2.3% 0.0% 4.2% 4.4% | |TERMINAL (d) | 0/47 (0%) 0/40 (0%) 0/42 (0%) 1/40 (3%) |1/40 (3%) 0/45 (0%) 2/43 (5%) 2/40 (5%) | |FIRST INCIDENCE | --- --- 710 727 (T) |733 (T) --- 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215 (e) P=0.483 P=0.468 |P=0.233 P=0.477N P=0.525 P=0.500 | |POLY 3 | P=0.228 (e) P=0.501 P=0.492 |P=0.241 P=0.483N P=0.527 P=0.510 | |POLY 1.5 | P=0.233 (e) P=0.503 P=0.497 |P=0.246 P=0.486N P=0.524 P=0.513 | |POLY 6 | P=0.221 (e) P=0.498 P=0.484 |P=0.235 P=0.482N P=0.527 P=0.505 | |LOGISTIC REGRESSION| P=0.230 (e) P=0.505 P=0.468 |P=0.233 (e) P=0.525 P=0.500 | |COCH-ARM / FISHERS | P=0.238 (e) P=0.505 P=0.505 |P=0.246 P=0.500N P=0.500 P=0.500 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 1/50 (2%) |19/50 (38%) 22/50 (44%) 21/50 (42%) 18/50 (36%) | |POLY-3 RATE (b) | 0/48.80 3/45.14 0/47.99 1/45.81 |19/44.00 22/47.89 21/47.87 18/45.39 | |POLY-3 PERCENT (g) | 0.0% 6.7% 0.0% 2.2% |43.2% 45.9% 43.9% 39.7% | |TERMINAL (d) | 0/48 (0%) 3/40 (8%) 0/42 (0%) 1/40 (3%) |18/40 (45%) 22/45 (49%) 20/43 (47%) 17/40 (43%) | |FIRST INCIDENCE | --- 727 (T) --- 727 (T) |722 733 (T) 625 706 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.592 P=0.091 (e) P=0.464 |P=0.436N P=0.534 P=0.537 P=0.502N | |POLY 3 | P=0.604 P=0.106 (e) P=0.487 |P=0.359N P=0.478 P=0.557 P=0.451N | |POLY 1.5 | P=0.617 P=0.111 (e) P=0.493 |P=0.345N P=0.457 P=0.537 P=0.442N | |POLY 6 | P=0.587 P=0.100 (e) P=0.480 |P=0.385N P=0.487 P=0.564 P=0.473N | |LOGISTIC REGRESSION| (e) P=0.091 (e) P=0.464 |P=0.422N P=0.500 P=0.542 P=0.513N | |COCH-ARM / FISHERS | P=0.634 P=0.121 (e) P=0.500 |P=0.385N P=0.342 P=0.419 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 18/50 (36%) 14/50 (28%) 14/50 (28%) |2/50 (4%) 6/50 (12%) 6/50 (12%) 13/50 (26%) | |POLY-3 RATE (b) | 9/48.80 18/47.35 14/48.08 14/47.41 |2/44.05 6/48.30 6/48.29 13/48.27 | |POLY-3 PERCENT (g) | 18.4% 38.0% 29.1% 29.5% |4.5% 12.4% 12.4% 26.9% | |TERMINAL (d) | 9/48 (19%) 14/40 (35%) 12/42 (29%) 10/40 (25%) |1/40 (3%) 5/45 (11%) 4/43 (9%) 8/40 (20%) | |FIRST INCIDENCE | 727 (T) 419 710 447 |709 615 469 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.189 P=0.013 * P=0.099 P=0.089 |P<0.001 ** P=0.177 P=0.165 P=0.004 ** | |POLY 3 | P=0.272 P=0.026 * P=0.160 P=0.150 |P=0.002 ** P=0.165 P=0.165 P=0.003 ** | |POLY 1.5 | P=0.288 P=0.029 * P=0.165 P=0.159 |P<0.001 ** P=0.160 P=0.160 P=0.003 ** | |POLY 6 | P=0.251 P=0.023 * P=0.151 P=0.138 |P=0.002 ** P=0.169 P=0.166 P=0.003 ** | |LOGISTIC REGRESSION| P=0.316 P=0.043 * P=0.127 P=0.184 |P<0.001 ** P=0.151 P=0.129 P<0.001 ** | |COCH-ARM / FISHERS | P=0.306 P=0.035 * P=0.171 P=0.171 |P<0.001 ** P=0.134 P=0.134 P=0.002 ** | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 1/45.14 0/47.99 1/45.81 |0/43.96 2/47.89 1/47.49 2/45.29 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 2.2% |0.0% 4.2% 2.1% 4.4% | |TERMINAL (d) | 0/48 (0%) 1/40 (3%) 0/42 (0%) 1/40 (3%) |0/40 (0%) 2/45 (4%) 1/43 (2%) 2/40 (5%) | |FIRST INCIDENCE | --- 727 (T) --- 727 (T) |--- 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376 P=0.464 (e) P=0.464 |P=0.233 P=0.265 P=0.514 P=0.238 | |POLY 3 | P=0.388 P=0.484 (e) P=0.487 |P=0.256 P=0.257 P=0.515 P=0.244 | |POLY 1.5 | P=0.396 P=0.491 (e) P=0.493 |P=0.259 P=0.254 P=0.514 P=0.245 | |POLY 6 | P=0.378 P=0.477 (e) P=0.480 |P=0.251 P=0.258 P=0.515 P=0.240 | |LOGISTIC REGRESSION| (e) P=0.464 (e) P=0.464 |(e) P=0.265 P=0.514 P=0.238 | |COCH-ARM / FISHERS | P=0.405 P=0.500 (e) P=0.500 |P=0.246 P=0.247 P=0.500 P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart: Myocardium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 3/50 (6%) 1/50 (2%) |3/50 (6%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/48.80 0/45.14 3/47.99 1/45.81 |3/44.55 1/47.89 1/47.49 1/45.41 | |POLY-3 PERCENT (g) | 2.1% 0.0% 6.3% 2.2% |6.7% 2.1% 2.1% 2.2% | |TERMINAL (d) | 1/48 (2%) 0/40 (0%) 3/42 (7%) 1/40 (3%) |2/40 (5%) 1/45 (2%) 1/43 (2%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) 727 (T) |544 733 (T) 733 (T) 700 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.422 P=0.536N P=0.259 P=0.720 |P=0.247N P=0.271N P=0.282N P=0.306N | |POLY 3 | P=0.451 P=0.516N P=0.300 P=0.746 |P=0.247N P=0.280N P=0.283N P=0.298N | |POLY 1.5 | P=0.460 P=0.509N P=0.303 P=0.752 |P=0.245N P=0.283N P=0.284N P=0.295N | |POLY 6 | P=0.438 P=0.523N P=0.294 P=0.738 |P=0.250N P=0.280N P=0.285N P=0.305N | |LOGISTIC REGRESSION| P=0.422 (e) P=0.259 P=0.720 |P=0.246N P=0.314N P=0.313N P=0.310N | |COCH-ARM / FISHERS | P=0.470 P=0.500N P=0.309 P=0.753N |P=0.242N P=0.309N P=0.309N P=0.309N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Heart: Valve | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |2/50 (4%) 4/50 (8%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.80 1/45.95 1/48.11 2/46.99 |2/45.11 4/48.63 0/47.49 1/46.24 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.1% 4.3% |4.4% 8.2% 0.0% 2.2% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 2/45 (4%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 419 697 447 |544 600 --- 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.151 P=0.500 P=0.487 P=0.237 |P=0.199N P=0.389 P=0.221N P=0.480N | |POLY 3 | P=0.148 P=0.488 P=0.497 P=0.229 |P=0.189N P=0.373 P=0.226N P=0.491N | |POLY 1.5 | P=0.151 P=0.493 P=0.499 P=0.233 |P=0.187N P=0.368 P=0.226N P=0.487N | |POLY 6 | P=0.143 P=0.482 P=0.495 P=0.223 |P=0.195N P=0.375 P=0.229N P=0.500N | |LOGISTIC REGRESSION| P=0.144 P=0.609 P=0.502 P=0.292 |P=0.307N P=0.238 P=0.334N P=0.712N | |COCH-ARM / FISHERS | P=0.153 P=0.500 P=0.500 P=0.247 |P=0.199N P=0.339 P=0.247N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Intestine Small, Duodenum: Epithelium | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/48.80 0/45.14 0/47.27 0/45.81 |0/43.96 0/47.89 0/47.49 0/44.29 | |POLY-3 PERCENT (g) | 4.1% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/39 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.132N P=0.280N P=0.268N P=0.280N |(e) (e) (e) (e) | |POLY 3 | P=0.107N P=0.255N P=0.245N P=0.252N |(e) (e) (e) (e) | |POLY 1.5 | P=0.110N P=0.248N P=0.243N P=0.246N |(e) (e) (e) (e) | |POLY 6 | P=0.104N P=0.264N P=0.247N P=0.260N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.132N (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.116N P=0.247N P=0.253N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Intestine Small, Jejunum: Peyer's Patch | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 1/47.99 0/45.81 |2/43.96 0/47.89 2/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.1% 0.0% |4.6% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 1/42 (2%) 0/40 (0%) |2/40 (5%) 0/45 (0%) 2/43 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 727 (T) --- |733 (T) --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.675 (e) P=0.473 (e) |P=0.251N P=0.213N P=0.669N P=0.238N | |POLY 3 | P=0.675 (e) P=0.497 (e) |P=0.255N P=0.219N P=0.666N P=0.231N | |POLY 1.5 | P=0.684 (e) P=0.498 (e) |P=0.251N P=0.222N P=0.669N P=0.229N | |POLY 6 | P=0.663 (e) P=0.494 (e) |P=0.260N P=0.217N P=0.666N P=0.234N | |LOGISTIC REGRESSION| (e) (e) P=0.473 (e) |P=0.251N (e) P=0.669N (e) | |COCH-ARM / FISHERS | P=0.695 (e) P=0.500 (e) |P=0.247N P=0.247N P=0.691N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 28/50 (56%) 30/50 (60%) 9/50 (18%) |2/50 (4%) 3/50 (6%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 15/48.80 28/47.42 30/48.38 9/47.10 |2/43.96 3/48.03 1/47.49 2/45.29 | |POLY-3 PERCENT (g) | 30.7% 59.1% 62.0% 19.1% |4.6% 6.3% 2.1% 4.4% | |TERMINAL (d) | 15/48 (31%) 23/40 (58%) 27/42 (64%) 6/40 (15%) |2/40 (5%) 2/45 (4%) 1/43 (2%) 2/40 (5%) | |FIRST INCIDENCE | 727 (T) 419 682 456 |733 (T) 698 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.121N P<0.001 ** P<0.001 ** P=0.246N |P=0.514N P=0.551 P=0.475N P=0.695 | |POLY 3 | P=0.039N* P=0.004 ** P<0.001 ** P=0.140N |P=0.491N P=0.540 P=0.473N P=0.683N | |POLY 1.5 | P=0.033N* P=0.004 ** P<0.001 ** P=0.131N |P=0.489N P=0.534 P=0.476N P=0.681N | |POLY 6 | P=0.051N P=0.003 ** P<0.001 ** P=0.154N |P=0.497N P=0.544 P=0.473N P=0.689N | |LOGISTIC REGRESSION| P=0.040N* P=0.005 ** P<0.001 ** P=0.118N |P=0.505N P=0.539 P=0.475N P=0.695 | |COCH-ARM / FISHERS | P=0.036N* P=0.007 ** P=0.002 ** P=0.121N |P=0.500N P=0.500 P=0.500N P=0.691N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 6/50 (12%) 3/50 (6%) |4/50 (8%) 1/50 (2%) 5/50 (10%) 2/50 (4%) | |POLY-3 RATE (b) | 2/48.80 5/45.57 6/48.02 3/46.99 |4/45.11 1/47.89 5/47.55 2/46.61 | |POLY-3 PERCENT (g) | 4.1% 11.0% 12.5% 6.4% |8.9% 2.1% 10.5% 4.3% | |TERMINAL (d) | 2/48 (4%) 4/40 (10%) 5/42 (12%) 1/40 (3%) |2/40 (5%) 1/45 (2%) 4/43 (9%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 601 720 447 |544 733 (T) 717 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.430 P=0.157 P=0.099 P=0.449 |P=0.427N P=0.154N P=0.546 P=0.327N | |POLY 3 | P=0.477 P=0.190 P=0.128 P=0.483 |P=0.419N P=0.161N P=0.533 P=0.322N | |POLY 1.5 | P=0.489 P=0.200 P=0.131 P=0.491 |P=0.412N P=0.162N P=0.534 P=0.318N | |POLY 6 | P=0.458 P=0.179 P=0.124 P=0.471 |P=0.428N P=0.163N P=0.526 P=0.331N | |LOGISTIC REGRESSION| P=0.520 P=0.208 P=0.111 P=0.601 |P=0.484N P=0.208N P=0.488 P=0.446N | |COCH-ARM / FISHERS | P=0.501 P=0.218 P=0.134 P=0.500 |P=0.420N P=0.181N P=0.500 P=0.339N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 3/50 (6%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 3/45.68 0/47.99 1/46.22 |0/43.96 3/47.89 1/47.55 0/45.29 | |POLY-3 PERCENT (g) | 4.1% 6.6% 0.0% 2.2% |0.0% 6.3% 2.1% 0.0% | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 3/45 (7%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 626 --- 608 |--- 733 (T) 717 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.273N P=0.430 P=0.268N P=0.547N |P=0.375N P=0.143 P=0.514 (e) | |POLY 3 | P=0.252N P=0.470 P=0.241N P=0.519N |P=0.344N P=0.135 P=0.516 (e) | |POLY 1.5 | P=0.248N P=0.482 P=0.239N P=0.511N |P=0.343N P=0.133 P=0.514 (e) | |POLY 6 | P=0.258N P=0.458 P=0.245N P=0.529N |P=0.349N P=0.136 P=0.516 (e) | |LOGISTIC REGRESSION| P=0.228N P=0.522 (e) P=0.468N |P=0.368N P=0.143 P=0.512 (e) | |COCH-ARM / FISHERS | P=0.242N P=0.500 P=0.247N P=0.500N |P=0.366N P=0.121 P=0.500 (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 45/50 (90%) 36/50 (72%) 46/50 (92%) 38/50 (76%) |13/50 (26%) 16/50 (32%) 15/50 (30%) 17/50 (34%) | |POLY-3 RATE (b) | 45/48.80 36/45.50 46/49.20 38/46.93 |13/45.61 16/48.59 15/48.27 17/45.75 | |POLY-3 PERCENT (g) | 92.2% 79.1% 93.5% 81.0% |28.5% 32.9% 31.1% 37.2% | |TERMINAL (d) | 45/48 (94%) 35/40 (88%) 39/42 (93%) 34/40 (85%) |10/40 (25%) 14/45 (31%) 13/43 (30%) 16/40 (40%) | |FIRST INCIDENCE | 727 (T) 626 616 626 |243 615 618 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.352 P=0.408N P=0.052 P=0.571 |P=0.229 P=0.468 P=0.503 P=0.264 | |POLY 3 | P=0.158N P=0.049N* P=0.560 P=0.081N |P=0.244 P=0.405 P=0.482 P=0.255 | |POLY 1.5 | P=0.152N P=0.030N* P=0.535 P=0.064N |P=0.262 P=0.394 P=0.475 P=0.270 | |POLY 6 | P=0.174N P=0.090N P=0.592 P=0.111N |P=0.220 P=0.414 P=0.483 P=0.234 | |LOGISTIC REGRESSION| P=0.337N P=0.198N P=0.429 P=0.238N |P=0.271 P=0.344 P=0.423 P=0.280 | |COCH-ARM / FISHERS | P=0.165N P=0.020N* P=0.500 P=0.054N |P=0.258 P=0.330 P=0.412 P=0.257 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 6/50 (12%) 6/50 (12%) 4/50 (8%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 8/48.80 6/46.13 6/48.78 4/45.81 |1/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 16.4% 13.0% 12.3% 8.7% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/48 (17%) 4/40 (10%) 5/42 (12%) 4/40 (10%) |1/40 (3%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 419 427 727 (T) |733 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.220N P=0.518N P=0.484N P=0.277N |P=0.307N P=0.477N P=0.486N P=0.500N | |POLY 3 | P=0.171N P=0.431N P=0.387N P=0.210N |P=0.314N P=0.483N P=0.485N P=0.494N | |POLY 1.5 | P=0.163N P=0.413N P=0.385N P=0.196N |P=0.314N P=0.486N P=0.486N P=0.493N | |POLY 6 | P=0.184N P=0.453N P=0.396N P=0.229N |P=0.313N P=0.482N P=0.485N P=0.497N | |LOGISTIC REGRESSION| P=0.143N P=0.364N P=0.377N P=0.277N |P=0.307N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.152N P=0.387N P=0.387N P=0.178N |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 1/45.14 2/47.99 2/45.98 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 4.1% 2.2% 4.2% 4.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 2/42 (5%) 1/40 (3%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 682 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.471 P=0.564N P=0.646 P=0.629 |(e) (e) (e) (e) | |POLY 3 | P=0.513 P=0.527N P=0.687 P=0.672 |(e) (e) (e) (e) | |POLY 1.5 | P=0.519 P=0.516N P=0.690 P=0.681 |(e) (e) (e) (e) | |POLY 6 | P=0.504 P=0.539N P=0.682 P=0.660 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.504 P=0.564N P=0.646 P=0.684 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.526 P=0.500N P=0.691N P=0.691N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 45/50 (90%) 43/50 (86%) 50/50 (100%) 33/50 (66%) |3/50 (6%) 14/50 (28%) 18/50 (36%) 6/50 (12%) | |POLY-3 RATE (b) | 45/49.64 43/47.76 50/50.00 33/47.01 |3/44.92 14/48.89 18/48.48 6/45.91 | |POLY-3 PERCENT (g) | 90.7% 90.0% 100.0% 70.2% |6.7% 28.6% 37.1% 13.1% | |TERMINAL (d) | 44/48 (92%) 38/40 (95%) 42/42 (100%) 29/40 (73%) |2/40 (5%) 11/45 (24%) 15/43 (35%) 4/40 (10%) | |FIRST INCIDENCE | 397 419 427 608 |243 600 575 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.108N P=0.088 P=0.003 ** P=0.158N |P=0.417 P=0.010 * P<0.001 ** P=0.254 | |POLY 3 | P<0.001N** P=0.599N P=0.035 * P=0.008N** |P=0.456 P=0.005 ** P<0.001 ** P=0.253 | |POLY 1.5 | P<0.001N** P=0.510N P=0.033 * P=0.005N** |P=0.469 P=0.005 ** P<0.001 ** P=0.255 | |POLY 6 | P<0.001N** P=0.601 P=0.040 * P=0.012N* |P=0.437 P=0.006 ** P<0.001 ** P=0.248 | |LOGISTIC REGRESSION| P<0.001N** P=0.557N P=0.032 * P=0.009N** |P=0.441 P=0.003 ** P<0.001 ** P=0.213 | |COCH-ARM / FISHERS | P<0.001N** P=0.380N P=0.028 * P=0.004N** |P=0.443 P=0.003 ** P<0.001 ** P=0.243 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 0/47.99 2/45.81 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 2/40 (5%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- 727 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.199 |(e) (e) (e) (e) | |POLY 3 | P=0.044 * (e) (e) P=0.224 |(e) (e) (e) (e) | |POLY 1.5 | P=0.045 * (e) (e) P=0.229 |(e) (e) (e) (e) | |POLY 6 | P=0.044 * (e) (e) P=0.216 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.199 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 3/50 (6%) 7/50 (14%) 2/50 (4%) |3/50 (6%) 2/50 (4%) 6/50 (12%) 0/50 (0%) | |POLY-3 RATE (b) | 8/48.80 3/45.14 7/47.99 2/45.81 |3/43.96 2/47.89 6/47.49 0/45.29 | |POLY-3 PERCENT (g) | 16.4% 6.7% 14.6% 4.4% |6.8% 4.2% 12.6% 0.0% | |TERMINAL (d) | 8/48 (17%) 3/40 (8%) 7/42 (17%) 2/40 (5%) |3/40 (8%) 2/45 (4%) 6/43 (14%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) |733 (T) 733 (T) 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.118N P=0.167N P=0.611 P=0.085N |P=0.192N P=0.446N P=0.278 P=0.121N | |POLY 3 | P=0.082N P=0.126N P=0.514N P=0.057N |P=0.184N P=0.461N P=0.282 P=0.113N | |POLY 1.5 | P=0.078N P=0.115N P=0.507N P=0.052N |P=0.178N P=0.467N P=0.278 P=0.112N | |POLY 6 | P=0.088N P=0.139N P=0.527N P=0.064N |P=0.192N P=0.458N P=0.281 P=0.116N | |LOGISTIC REGRESSION| P=0.118N P=0.167N P=0.611 P=0.085N |P=0.192N P=0.446N P=0.278 (e) | |COCH-ARM / FISHERS | P=0.076N P=0.100N P=0.500N P=0.046N* |P=0.186N P=0.500N P=0.243 P=0.121N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 5/50 (10%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/48.80 2/45.14 5/47.99 1/45.81 |0/43.96 1/47.89 0/47.49 1/45.29 | |POLY-3 PERCENT (g) | 6.2% 4.4% 10.4% 2.2% |0.0% 2.1% 0.0% 2.2% | |TERMINAL (d) | 3/48 (6%) 2/40 (5%) 5/42 (12%) 1/40 (3%) |0/40 (0%) 1/45 (2%) 0/43 (0%) 1/40 (3%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) |--- 733 (T) --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386N P=0.583N P=0.286 P=0.373N |P=0.397 P=0.523 (e) P=0.500 | |POLY 3 | P=0.340N P=0.535N P=0.348 P=0.329N |P=0.415 P=0.517 (e) P=0.506 | |POLY 1.5 | P=0.330N P=0.521N P=0.352 P=0.319N |P=0.417 P=0.514 (e) P=0.507 | |POLY 6 | P=0.356N P=0.551N P=0.340 P=0.342N |P=0.411 P=0.518 (e) P=0.503 | |LOGISTIC REGRESSION| P=0.386N P=0.583N P=0.286 P=0.373N |(e) P=0.523 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.318N P=0.500N P=0.357 P=0.309N |P=0.405 P=0.500 (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.80 2/45.50 0/47.99 0/45.81 |1/44.05 0/47.89 3/47.49 0/45.29 | |POLY-3 PERCENT (g) | 2.1% 4.4% 0.0% 0.0% |2.3% 0.0% 6.3% 0.0% | |TERMINAL (d) | 1/48 (2%) 1/40 (3%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 3/43 (7%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 626 --- --- |709 --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.209N P=0.446 P=0.527N P=0.536N |P=0.512N P=0.486N P=0.333 P=0.510N | |POLY 3 | P=0.197N P=0.476 P=0.503N P=0.513N |P=0.506N P=0.483N P=0.333 P=0.494N | |POLY 1.5 | P=0.193N P=0.485 P=0.502N P=0.507N |P=0.500N P=0.486N P=0.330 P=0.493N | |POLY 6 | P=0.203N P=0.465 P=0.506N P=0.520N |P=0.515N P=0.482N P=0.332 P=0.498N | |LOGISTIC REGRESSION| P=0.183N P=0.524 (e) (e) |P=0.501N P=0.493N P=0.332 P=0.495N | |COCH-ARM / FISHERS | P=0.188N P=0.500 P=0.500N P=0.500N |P=0.500N P=0.500N P=0.309 P=0.500N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 5/50 (10%) 4/50 (8%) |16/50 (32%) 12/50 (24%) 27/50 (54%) 25/50 (50%) | |POLY-3 RATE (b) | 2/48.80 4/45.14 5/48.16 4/45.81 |16/43.96 12/47.89 27/47.58 25/45.29 | |POLY-3 PERCENT (g) | 4.1% 8.9% 10.4% 8.7% |36.4% 25.1% 56.8% 55.2% | |TERMINAL (d) | 2/48 (4%) 4/40 (10%) 4/42 (10%) 4/40 (10%) |16/40 (40%) 12/45 (27%) 26/43 (61%) 25/40 (63%) | |FIRST INCIDENCE | 727 (T) 727 (T) 682 727 (T) |733 (T) 733 (T) 709 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.239 P=0.257 P=0.175 P=0.257 |P=0.003 ** P=0.143N P=0.036 * P=0.038 * | |POLY 3 | P=0.279 P=0.302 P=0.212 P=0.309 |P=0.005 ** P=0.170N P=0.038 * P=0.054 | |POLY 1.5 | P=0.293 P=0.316 P=0.214 P=0.321 |P=0.006 ** P=0.183N P=0.036 * P=0.061 | |POLY 6 | P=0.259 P=0.287 P=0.207 P=0.293 |P=0.003 ** P=0.164N P=0.037 * P=0.045 * | |LOGISTIC REGRESSION| P=0.263 P=0.257 P=0.212 P=0.257 |P=0.002 ** P=0.143N P=0.033 * P=0.038 * | |COCH-ARM / FISHERS | P=0.309 P=0.339 P=0.218 P=0.339 |P=0.007 ** P=0.252N P=0.021 * P=0.052 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 12/50 (24%) 12/50 (24%) 7/50 (14%) |20/50 (40%) 20/50 (40%) 16/50 (32%) 11/50 (22%) | |POLY-3 RATE (b) | 9/48.80 12/45.64 12/48.14 7/46.48 |20/45.02 20/48.30 16/47.87 11/45.80 | |POLY-3 PERCENT (g) | 18.4% 26.3% 24.9% 15.1% |44.4% 41.4% 33.4% 24.0% | |TERMINAL (d) | 9/48 (19%) 11/40 (28%) 11/42 (26%) 6/40 (15%) |18/40 (45%) 19/45 (42%) 15/43 (35%) 10/40 (25%) | |FIRST INCIDENCE | 727 (T) 576 689 500 |242 615 625 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.407N P=0.172 P=0.206 P=0.541N |P=0.024N* P=0.397N P=0.186N P=0.042N* | |POLY 3 | P=0.309N P=0.253 P=0.299 P=0.434N |P=0.017N* P=0.466N P=0.190N P=0.031N* | |POLY 1.5 | P=0.293N P=0.275 P=0.306 P=0.416N |P=0.016N* P=0.486N P=0.200N P=0.030N* | |POLY 6 | P=0.336N P=0.228 P=0.288 P=0.460N |P=0.019N* P=0.452N P=0.188N P=0.033N* | |LOGISTIC REGRESSION| P=0.304N P=0.237 P=0.270 P=0.407N |P=0.016N* P=0.482N P=0.198N P=0.033N* | |COCH-ARM / FISHERS | P=0.275N P=0.312 P=0.312 P=0.393N |P=0.020N* P=0.581N P=0.266N P=0.041N* | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 8/50 (16%) 9/50 (18%) 7/50 (14%) |4/50 (8%) 1/50 (2%) 4/50 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 9/48.80 8/45.50 9/47.99 7/45.81 |4/43.96 1/47.89 4/47.49 3/45.75 | |POLY-3 PERCENT (g) | 18.4% 17.6% 18.8% 15.3% |9.1% 2.1% 8.4% 6.6% | |TERMINAL (d) | 9/48 (19%) 7/40 (18%) 9/42 (21%) 7/40 (18%) |4/40 (10%) 1/45 (2%) 4/43 (9%) 2/40 (5%) | |FIRST INCIDENCE | 727 (T) 626 727 (T) 727 (T) |733 (T) 733 (T) 733 (T) 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.490N P=0.552 P=0.479 P=0.550N |P=0.566 P=0.146N P=0.604N P=0.496N | |POLY 3 | P=0.400N P=0.563N P=0.587 P=0.447N |P=0.577 P=0.154N P=0.600N P=0.478N | |POLY 1.5 | P=0.382N P=0.538N P=0.595 P=0.423N |P=0.578N P=0.158N P=0.605N P=0.477N | |POLY 6 | P=0.426N P=0.589N P=0.573 P=0.478N |P=0.570 P=0.152N P=0.601N P=0.483N | |LOGISTIC REGRESSION| P=0.438N P=0.585N P=0.479 P=0.550N |P=0.576N P=0.146N P=0.604N P=0.485N | |COCH-ARM / FISHERS | P=0.362N P=0.500N P=0.602N P=0.393N |P=0.580 P=0.181N P=0.643N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 5/50 (10%) 1/50 (2%) |2/50 (4%) 2/50 (4%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 3/48.80 4/45.97 5/48.34 1/45.81 |2/45.89 2/47.89 3/48.63 0/45.29 | |POLY-3 PERCENT (g) | 6.2% 8.7% 10.3% 2.2% |4.4% 4.2% 6.2% 0.0% | |TERMINAL (d) | 3/48 (6%) 2/40 (5%) 3/42 (7%) 1/40 (3%) |0/40 (0%) 2/45 (4%) 1/43 (2%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 511 650 727 (T) |242 733 (T) 469 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.292N P=0.417 P=0.301 P=0.373N |P=0.198N P=0.664N P=0.531 P=0.231N | |POLY 3 | P=0.261N P=0.468 P=0.352 P=0.329N |P=0.207N P=0.678N P=0.526 P=0.240N | |POLY 1.5 | P=0.249N P=0.480 P=0.355 P=0.319N |P=0.202N P=0.680N P=0.522 P=0.237N | |POLY 6 | P=0.279N P=0.453 P=0.347 P=0.342N |P=0.214N P=0.677N P=0.529 P=0.244N | |LOGISTIC REGRESSION| P=0.225N P=0.548 P=0.357 P=0.373N |P=0.358N P=0.405 P=0.117 P=0.573N | |COCH-ARM / FISHERS | P=0.233N P=0.500 P=0.357 P=0.309N |P=0.199N P=0.691N P=0.500 P=0.247N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 7/50 (14%) 4/50 (8%) 4/50 (8%) |4/50 (8%) 5/50 (10%) 3/50 (6%) 5/50 (10%) | |POLY-3 RATE (b) | 6/48.80 7/45.14 4/48.16 4/45.81 |4/44.92 5/47.89 3/47.49 5/45.91 | |POLY-3 PERCENT (g) | 12.3% 15.5% 8.3% 8.7% |8.9% 10.4% 6.3% 10.9% | |TERMINAL (d) | 6/48 (13%) 7/40 (18%) 3/42 (7%) 4/40 (10%) |3/40 (8%) 5/45 (11%) 3/43 (7%) 3/40 (8%) | |FIRST INCIDENCE | 727 (T) 727 (T) 682 727 (T) |242 733 (T) 733 (T) 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.315N P=0.361 P=0.449N P=0.488N |P=0.466 P=0.566 P=0.465N P=0.504 | |POLY 3 | P=0.253N P=0.440 P=0.378N P=0.410N |P=0.489 P=0.540 P=0.470N P=0.514 | |POLY 1.5 | P=0.243N P=0.464 P=0.374N P=0.393N |P=0.493 P=0.534 P=0.472N P=0.516 | |POLY 6 | P=0.269N P=0.413 P=0.386N P=0.434N |P=0.483 P=0.543 P=0.471N P=0.508 | |LOGISTIC REGRESSION| P=0.284N P=0.361 P=0.381N P=0.488N |P=0.471 P=0.461 P=0.561N P=0.466 | |COCH-ARM / FISHERS | P=0.230N P=0.500 P=0.370N P=0.370N |P=0.483 P=0.500 P=0.500N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/49.64 1/45.83 0/47.99 0/45.81 |1/43.96 1/48.03 1/47.81 2/46.12 | |POLY-3 PERCENT (g) | 2.0% 2.2% 0.0% 0.0% |2.3% 2.1% 2.1% 4.3% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |1/40 (3%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 397 491 --- --- |733 (T) 698 645 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.238N P=0.758 P=0.500N P=0.500N |P=0.346 P=0.737N P=0.745N P=0.508 | |POLY 3 | P=0.241N P=0.742 P=0.507N P=0.516N |P=0.359 P=0.740N P=0.742N P=0.517 | |POLY 1.5 | P=0.239N P=0.749 P=0.504N P=0.510N |P=0.360 P=0.744N P=0.744N P=0.516 | |POLY 6 | P=0.243N P=0.735 P=0.510N P=0.524N |P=0.357 P=0.738N P=0.741N P=0.515 | |LOGISTIC REGRESSION| P=0.243N P=0.633N (e) (e) |P=0.318 P=0.752N P=0.762 P=0.477 | |COCH-ARM / FISHERS | P=0.236N P=0.753N P=0.500N P=0.500N |P=0.351 P=0.753N P=0.753N P=0.500 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 6/50 (12%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 6/45.57 2/47.99 0/45.81 |1/44.92 2/48.18 1/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 13.2% 4.2% 0.0% |2.2% 4.2% 2.1% 0.0% | |TERMINAL (d) | 0/48 (0%) 5/40 (13%) 2/42 (5%) 0/40 (0%) |0/40 (0%) 1/45 (2%) 1/43 (2%) 0/40 (0%) | |FIRST INCIDENCE | --- 601 727 (T) --- |243 653 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.277N P=0.011 * P=0.210 (e) |P=0.249N P=0.531 P=0.745N P=0.488N | |POLY 3 | P=0.264N P=0.012 * P=0.234 (e) |P=0.245N P=0.524 P=0.748N P=0.498N | |POLY 1.5 | P=0.248N P=0.013 * P=0.236 (e) |P=0.243N P=0.520 P=0.749N P=0.496N | |POLY 6 | P=0.287N P=0.011 * P=0.230 (e) |P=0.249N P=0.528 P=0.749N P=0.502N | |LOGISTIC REGRESSION| P=0.235N P=0.016 * P=0.210 (e) |P=0.332N P=0.304 P=0.608 P=0.811N | |COCH-ARM / FISHERS | P=0.232N P=0.013 * P=0.247 (e) |P=0.247N P=0.500 P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/50 (2%) 2/50 (4%) 3/50 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 1/47.99 1/45.81 |1/43.96 2/47.89 3/47.49 2/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.1% 2.2% |2.3% 4.2% 6.3% 4.4% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 1/42 (2%) 1/40 (3%) |1/40 (3%) 2/45 (4%) 3/43 (7%) 2/40 (5%) | |FIRST INCIDENCE | --- --- 727 (T) 727 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.214 (e) P=0.473 P=0.464 |P=0.388 P=0.541 P=0.331 P=0.500 | |POLY 3 | P=0.226 (e) P=0.497 P=0.487 |P=0.410 P=0.530 P=0.334 P=0.510 | |POLY 1.5 | P=0.231 (e) P=0.498 P=0.493 |P=0.416 P=0.525 P=0.331 P=0.513 | |POLY 6 | P=0.219 (e) P=0.494 P=0.480 |P=0.400 P=0.532 P=0.333 P=0.505 | |LOGISTIC REGRESSION| (e) (e) P=0.473 P=0.464 |P=0.388 P=0.541 P=0.331 P=0.500 | |COCH-ARM / FISHERS | P=0.236 (e) P=0.500 P=0.500 |P=0.404 P=0.500 P=0.309 P=0.500 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 4/50 (8%) 2/50 (4%) |2/50 (4%) 3/50 (6%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 2/48.80 1/45.14 4/48.38 2/45.81 |2/43.96 3/47.89 2/47.49 2/45.29 | |POLY-3 PERCENT (g) | 4.1% 2.2% 8.3% 4.4% |4.6% 6.3% 4.2% 4.4% | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 3/42 (7%) 2/40 (5%) |2/40 (5%) 3/45 (7%) 2/43 (5%) 2/40 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) 616 727 (T) |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.419 P=0.564N P=0.289 P=0.627 |P=0.539N P=0.554 P=0.669N P=0.695 | |POLY 3 | P=0.455 P=0.527N P=0.334 P=0.671 |P=0.515N P=0.539 P=0.666N P=0.683N | |POLY 1.5 | P=0.466 P=0.516N P=0.336 P=0.681 |P=0.511N P=0.533 P=0.669N P=0.681N | |POLY 6 | P=0.440 P=0.539N P=0.329 P=0.657 |P=0.522N P=0.542 P=0.666N P=0.689N | |LOGISTIC REGRESSION| P=0.466 P=0.564N P=0.341 P=0.627 |P=0.539N P=0.554 P=0.669N P=0.695 | |COCH-ARM / FISHERS | P=0.477 P=0.500N P=0.339 P=0.691N |P=0.523N P=0.500 P=0.691N P=0.691N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lung: Serosa | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 0/45.14 1/47.99 0/45.81 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 4.1% 0.0% 2.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 0/40 (0%) 1/42 (2%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215N P=0.280N P=0.547N P=0.280N |(e) (e) (e) (e) | |POLY 3 | P=0.185N P=0.255N P=0.506N P=0.252N |(e) (e) (e) (e) | |POLY 1.5 | P=0.186N P=0.248N P=0.503N P=0.246N |(e) (e) (e) (e) | |POLY 6 | P=0.185N P=0.264N P=0.511N P=0.260N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.215N (e) P=0.547N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.188N P=0.247N P=0.500N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/49 (0%) 1/48 (2%) 0/50 (0%) |3/49 (6%) 1/48 (2%) 2/50 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 1/46.80 0/44.14 1/46.78 0/45.81 |3/43.55 1/46.48 2/47.49 1/44.57 | |POLY-3 PERCENT (g) | 2.1% 0.0% 2.1% 0.0% |6.9% 2.2% 4.2% 2.2% | |TERMINAL (d) | 1/46 (2%) 0/39 (0%) 1/41 (2%) 0/40 (0%) |3/40 (8%) 1/45 (2%) 2/43 (5%) 1/40 (3%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) --- |733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.427N P=0.533N P=0.736 P=0.528N |P=0.286N P=0.264N P=0.467N P=0.305N | |POLY 3 | P=0.398N P=0.512N P=0.760 P=0.504N |P=0.283N P=0.283N P=0.461N P=0.297N | |POLY 1.5 | P=0.398N P=0.505N P=0.760N P=0.499N |P=0.279N P=0.287N P=0.462N P=0.294N | |POLY 6 | P=0.399N P=0.519N P=0.758 P=0.511N |P=0.290N P=0.280N P=0.463N P=0.303N | |LOGISTIC REGRESSION| P=0.427N (e) P=0.736 (e) |P=0.286N P=0.264N P=0.467N P=0.305N | |COCH-ARM / FISHERS | P=0.399N P=0.495N P=0.753N P=0.490N |P=0.276N P=0.316N P=0.490N P=0.309N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/6 (50%) 1/2 (50%) 0/3 (0%) 1/3 (33%) |1/5 (20%) 0/1 (0%) 1/6 (17%) 0/2 (0%) | |POLY-3 RATE (b) | 3/5.64 1/2.00 0/3.00 1/3.00 |1/4.07 0/1.00 1/6.00 0/1.54 | |POLY-3 PERCENT (g) | 53.2% 50.0% 0.0% 33.3% |24.6% 0.0% 16.7% 0.0% | |TERMINAL (d) | 3/5 (60%) 1/2 (50%) 0/3 (0%) 1/3 (33%) |1/2 (50%) 0/1 (0%) 1/6 (17%) 0/1 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) --- 727 (T) |733 (T) --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.275N P=0.712N P=0.189N P=0.500N |P=0.393N P=0.638N P=0.500N P=0.638N | |POLY 3 | P=0.331N P=0.748N P=0.195N P=0.558N |P=0.480N P=0.780N P=0.672N P=0.688N | |POLY 1.5 | P=0.340N P=0.754N P=0.207N P=0.570N |P=0.490N P=0.786N P=0.694N P=0.681N | |POLY 6 | P=0.319N P=0.736N P=0.177N P=0.539N |P=0.464N P=0.767N P=0.637N P=0.697N | |LOGISTIC REGRESSION| P=0.275N P=0.712N (e) P=0.500N |P=0.393N (e) P=0.500N (e) | |COCH-ARM / FISHERS | P=0.341N P=0.786N P=0.238N P=0.595N |P=0.500N P=0.833N P=0.727N P=0.714N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/6 (17%) 0/2 (0%) 2/3 (67%) 1/3 (33%) |3/5 (60%) 1/1 (100%) 2/6 (33%) 1/2 (50%) | |POLY-3 RATE (b) | 1/5.64 0/2.00 2/3.00 1/3.00 |3/4.73 1/1.00 2/6.00 1/2.00 | |POLY-3 PERCENT (g) | 17.7% 0.0% 66.7% 33.3% |63.4% 100.0% 33.3% 50.0% | |TERMINAL (d) | 1/5 (20%) 0/2 (0%) 2/3 (67%) 1/3 (33%) |1/2 (50%) 1/1 (100%) 2/6 (33%) 0/1 (0%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) 727 (T) |557 733 (T) 733 (T) 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.377 P=0.682N P=0.298 P=0.653 |P=0.259N P=0.399N P=0.205N P=0.368N | |POLY 3 | P=0.341 P=0.701N P=0.240 P=0.618 |P=0.403N P=0.668 P=0.364N P=0.681N | |POLY 1.5 | P=0.330 P=0.704N P=0.232 P=0.610 |P=0.415N P=0.650 P=0.380N P=0.689N | |POLY 6 | P=0.358 P=0.695N P=0.254 P=0.629 |P=0.383N P=0.698 P=0.339N P=0.667N | |LOGISTIC REGRESSION| P=0.377 (e) P=0.298 P=0.653 |P=0.447N P=0.625 P=0.592N P=0.709N | |COCH-ARM / FISHERS | P=0.312 P=0.750N P=0.226 P=0.583 |P=0.422N P=0.667 P=0.392N P=0.714N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Oral Mucosa | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 16/50 (32%) 21/50 (42%) 21/50 (42%) |20/50 (40%) 32/50 (64%) 35/50 (70%) 32/50 (64%) | |POLY-3 RATE (b) | 6/48.80 16/46.21 21/49.00 21/46.34 |20/45.11 32/48.43 35/49.44 32/46.50 | |POLY-3 PERCENT (g) | 12.3% 34.6% 42.9% 45.3% |44.3% 66.1% 70.8% 68.8% | |TERMINAL (d) | 6/48 (13%) 13/40 (33%) 18/42 (43%) 19/40 (48%) |18/40 (45%) 30/45 (67%) 31/43 (72%) 29/40 (73%) | |FIRST INCIDENCE | 727 (T) 511 427 652 |545 615 469 557 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** |P=0.014 * P=0.055 P=0.010 * P=0.014 * | |POLY 3 | P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** |P=0.022 * P=0.026 * P=0.007 ** P=0.013 * | |POLY 1.5 | P<0.001 ** P=0.010 * P<0.001 ** P<0.001 ** |P=0.026 * P=0.024 * P=0.006 ** P=0.015 * | |POLY 6 | P<0.001 ** P=0.007 ** P<0.001 ** P<0.001 ** |P=0.017 * P=0.026 * P=0.007 ** P=0.010 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** |P=0.024 * P=0.032 * P=0.005 ** P=0.018 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.014 * P<0.001 ** P<0.001 ** |P=0.022 * P=0.014 * P=0.002 ** P=0.014 * | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Oral Mucosa | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 8/50 (16%) 12/50 (24%) 10/50 (20%) |6/50 (12%) 15/50 (30%) 22/50 (44%) 15/50 (30%) | |POLY-3 RATE (b) | 4/48.80 8/45.86 12/49.00 10/46.06 |6/44.55 15/48.30 22/48.70 15/45.66 | |POLY-3 PERCENT (g) | 8.2% 17.5% 24.5% 21.7% |13.5% 31.1% 45.2% 32.9% | |TERMINAL (d) | 4/48 (8%) 6/40 (15%) 9/42 (21%) 9/40 (23%) |5/40 (13%) 14/45 (31%) 19/43 (44%) 14/40 (35%) | |FIRST INCIDENCE | 727 (T) 511 427 661 |545 615 575 628 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.041 * P=0.112 P=0.018 * P=0.037 * |P=0.032 * P=0.049 * P<0.001 ** P=0.026 * | |POLY 3 | P=0.054 P=0.149 P=0.027 * P=0.057 |P=0.039 * P=0.036 * P<0.001 ** P=0.025 * | |POLY 1.5 | P=0.061 P=0.160 P=0.027 * P=0.064 |P=0.044 * P=0.034 * P<0.001 ** P=0.027 * | |POLY 6 | P=0.046 * P=0.136 P=0.025 * P=0.050 |P=0.033 * P=0.037 * P<0.001 ** P=0.022 * | |LOGISTIC REGRESSION| P=0.071 P=0.171 P=0.029 * P=0.049 * |P=0.043 * P=0.035 * P<0.001 ** P=0.028 * | |COCH-ARM / FISHERS | P=0.072 P=0.178 P=0.027 * P=0.074 |P=0.041 * P=0.024 * P<0.001 ** P=0.024 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | |0/43.96 0/47.89 2/46.49 0/45.29 | |POLY-3 PERCENT (g) | |0.0% 0.0% 4.3% 0.0% | |TERMINAL (d) | |0/40 (0%) 0/45 (0%) 2/42 (5%) 0/40 (0%) | |FIRST INCIDENCE | |--- --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.590 (e) P=0.249 (e) | |POLY 3 | |P=0.594 (e) P=0.250 (e) | |POLY 1.5 | |P=0.601 (e) P=0.248 (e) | |POLY 6 | |P=0.584 (e) P=0.250 (e) | |LOGISTIC REGRESSION| |(e) (e) P=0.249 (e) | |COCH-ARM / FISHERS | |P=0.595 (e) P=0.242 (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |19/50 (38%) 23/50 (46%) 16/49 (33%) 17/50 (34%) | |POLY-3 RATE (b) | |19/43.96 23/48.18 16/46.49 17/47.21 | |POLY-3 PERCENT (g) | |43.2% 47.7% 34.4% 36.0% | |TERMINAL (d) | |19/40 (48%) 22/45 (49%) 16/42 (38%) 13/40 (33%) | |FIRST INCIDENCE | |733 (T) 653 733 (T) 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.274N P=0.454 P=0.263N P=0.412N | |POLY 3 | |P=0.173N P=0.411 P=0.260N P=0.312N | |POLY 1.5 | |P=0.178N P=0.385 P=0.272N P=0.323N | |POLY 6 | |P=0.176N P=0.429 P=0.260N P=0.311N | |LOGISTIC REGRESSION| |P=0.221N P=0.413 P=0.263N P=0.374N | |COCH-ARM / FISHERS | |P=0.240N P=0.272 P=0.365N P=0.418N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 2/50 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | |0/43.96 2/48.03 0/46.49 0/45.29 | |POLY-3 PERCENT (g) | |0.0% 4.2% 0.0% 0.0% | |TERMINAL (d) | |0/40 (0%) 1/45 (2%) 0/42 (0%) 0/40 (0%) | |FIRST INCIDENCE | |--- 698 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.410N P=0.263 (e) (e) | |POLY 3 | |P=0.384N P=0.258 (e) (e) | |POLY 1.5 | |P=0.385N P=0.254 (e) (e) | |POLY 6 | |P=0.385N P=0.260 (e) (e) | |LOGISTIC REGRESSION| |P=0.403N P=0.248 (e) (e) | |COCH-ARM / FISHERS | |P=0.406N P=0.247 (e) (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 0/47.99 0/45.81 |1/44.05 0/47.89 0/47.49 2/45.85 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 0.0% 0.0% 4.4% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |709 --- --- 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.236 P=0.486N P=0.486N P=0.497 | |POLY 3 | (e) (e) (e) (e) |P=0.242 P=0.483N P=0.485N P=0.514 | |POLY 1.5 | (e) (e) (e) (e) |P=0.243 P=0.486N P=0.487N P=0.515 | |POLY 6 | (e) (e) (e) (e) |P=0.240 P=0.482N P=0.486N P=0.511 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.230 P=0.493N P=0.493N P=0.489 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.245 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Acinus | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 0/47.99 0/45.81 |1/43.96 0/47.89 2/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |1/40 (3%) 0/45 (0%) 2/43 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |733 (T) --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.468N P=0.477N P=0.525 P=0.500N | |POLY 3 | (e) (e) (e) (e) |P=0.467N P=0.483N P=0.527 P=0.494N | |POLY 1.5 | (e) (e) (e) (e) |P=0.462N P=0.486N P=0.524 P=0.493N | |POLY 6 | (e) (e) (e) (e) |P=0.473N P=0.482N P=0.527 P=0.497N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.468N (e) P=0.525 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.500N P=0.500 P=0.500N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pancreas: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 0/47.99 0/45.81 |2/44.05 1/48.03 0/47.49 1/45.75 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.5% 2.1% 0.0% 2.2% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |1/40 (3%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |709 698 --- 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.373N P=0.468N P=0.224N P=0.500N | |POLY 3 | (e) (e) (e) (e) |P=0.369N P=0.470N P=0.221N P=0.487N | |POLY 1.5 | (e) (e) (e) (e) |P=0.368N P=0.475N P=0.223N P=0.486N | |POLY 6 | (e) (e) (e) (e) |P=0.370N P=0.468N P=0.221N P=0.491N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.379N P=0.483N P=0.222N P=0.505N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.367N P=0.500N P=0.247N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Parathyroid Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/43 (0%) 0/39 (0%) 0/44 (0%) 2/37 (5%) |0/43 (0%) 0/35 (0%) 0/40 (0%) 0/43 (0%) | |POLY-3 RATE (b) | 0/42.64 0/34.20 0/42.27 2/34.24 |0/38.11 0/34.14 0/38.00 0/38.92 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/42 (0%) 0/30 (0%) 0/37 (0%) 2/30 (7%) |0/35 (0%) 0/33 (0%) 0/34 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 727 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033 * (e) (e) P=0.168 |(e) (e) (e) (e) | |POLY 3 | P=0.036 * (e) (e) P=0.190 |(e) (e) (e) (e) | |POLY 1.5 | P=0.036 * (e) (e) P=0.195 |(e) (e) (e) (e) | |POLY 6 | P=0.036 * (e) (e) P=0.184 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.168 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.038 * (e) (e) P=0.211 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Peripheral Nerve: Axon | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 2/2 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 1/1.00 0/0.00 |0/0.00 0/0.00 0/0.00 2/2.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 100.0% 0.0% |0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 616 --- |--- --- --- 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 0/47 (0%) 3/50 (6%) |7/49 (14%) 7/50 (14%) 10/49 (20%) 9/49 (18%) | |POLY-3 RATE (b) | 0/48.80 1/44.95 0/45.31 3/45.81 |7/43.05 7/47.89 10/47.40 9/44.92 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 6.6% |16.3% 14.6% 21.1% 20.0% | |TERMINAL (d) | 0/48 (0%) 1/40 (3%) 0/41 (0%) 3/40 (8%) |6/39 (15%) 7/45 (16%) 8/42 (19%) 9/40 (23%) | |FIRST INCIDENCE | --- 727 (T) --- 727 (T) |709 733 (T) 575 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.035 * P=0.464 (e) P=0.091 |P=0.277 P=0.504N P=0.365 P=0.410 | |POLY 3 | P=0.041 * P=0.484 (e) P=0.108 |P=0.301 P=0.529N P=0.376 P=0.428 | |POLY 1.5 | P=0.043 * P=0.489 (e) P=0.113 |P=0.307 P=0.539N P=0.362 P=0.430 | |POLY 6 | P=0.040 * P=0.477 (e) P=0.102 |P=0.289 P=0.525N P=0.383 P=0.417 | |LOGISTIC REGRESSION| (e) P=0.464 (e) P=0.091 |P=0.300 P=0.520N P=0.342 P=0.407 | |COCH-ARM / FISHERS | P=0.045 * P=0.495 (e) P=0.121 |P=0.286 P=0.597N P=0.297 P=0.393 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 19/50 (38%) 18/50 (36%) 12/50 (24%) | | |POLY-3 RATE (b) | 17/49.16 19/46.80 18/48.35 12/45.99 | | |POLY-3 PERCENT (g) | 34.6% 40.6% 37.2% 26.1% | | |TERMINAL (d) | 16/48 (33%) 15/40 (38%) 15/42 (36%) 11/40 (28%) | | |FIRST INCIDENCE | 626 491 682 681 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.258N P=0.210 P=0.331 P=0.375N | | |POLY 3 | P=0.168N P=0.346 P=0.476 P=0.250N | | |POLY 1.5 | P=0.145N P=0.374 P=0.488 P=0.223N | | |POLY 6 | P=0.202N P=0.318 P=0.456 P=0.290N | | |LOGISTIC REGRESSION| P=0.142N P=0.387 P=0.482 P=0.268N | | |COCH-ARM / FISHERS | P=0.121N P=0.418 P=0.500 P=0.189N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 4/50 (8%) | | |POLY-3 RATE (b) | 2/48.80 2/45.49 1/47.99 4/45.99 | | |POLY-3 PERCENT (g) | 4.1% 4.4% 2.1% 8.7% | | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 1/42 (2%) 3/40 (8%) | | |FIRST INCIDENCE | 727 (T) 629 727 (T) 681 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188 P=0.633 P=0.547N P=0.262 | | |POLY 3 | P=0.217 P=0.668 P=0.506N P=0.311 | | |POLY 1.5 | P=0.222 P=0.678 P=0.503N P=0.322 | | |POLY 6 | P=0.210 P=0.657 P=0.511N P=0.296 | | |LOGISTIC REGRESSION| P=0.222 P=0.690N P=0.547N P=0.305 | | |COCH-ARM / FISHERS | P=0.227 P=0.691N P=0.500N P=0.339 | | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 1/50 (2%) | | |POLY-3 RATE (b) | 0/48.80 1/45.14 2/47.99 1/45.81 | | |POLY-3 PERCENT (g) | 0.0% 2.2% 4.2% 2.2% | | |TERMINAL (d) | 0/48 (0%) 1/40 (3%) 2/42 (5%) 1/40 (3%) | | |FIRST INCIDENCE | --- 727 (T) 727 (T) 727 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.328 P=0.464 P=0.210 P=0.464 | | |POLY 3 | P=0.342 P=0.484 P=0.234 P=0.487 | | |POLY 1.5 | P=0.353 P=0.491 P=0.236 P=0.493 | | |POLY 6 | P=0.327 P=0.477 P=0.230 P=0.480 | | |LOGISTIC REGRESSION| (e) P=0.464 P=0.210 P=0.464 | | |COCH-ARM / FISHERS | P=0.367 P=0.500 P=0.247 P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Seminal Vesicle | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 0/50 (0%) | | |POLY-3 RATE (b) | 0/48.80 1/45.14 3/48.14 0/45.81 | | |POLY-3 PERCENT (g) | 0.0% 2.2% 6.2% 0.0% | | |TERMINAL (d) | 0/48 (0%) 1/40 (3%) 2/42 (5%) 0/40 (0%) | | |FIRST INCIDENCE | --- 727 (T) 689 --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.593 P=0.464 P=0.106 (e) | | |POLY 3 | P=0.602 P=0.484 P=0.117 (e) | | |POLY 1.5 | P=0.617 P=0.491 P=0.118 (e) | | |POLY 6 | P=0.581 P=0.477 P=0.114 (e) | | |LOGISTIC REGRESSION| P=0.624 P=0.464 P=0.121 (e) | | |COCH-ARM / FISHERS | P=0.633N P=0.500 P=0.121 (e) | | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 1/45.14 0/47.99 0/45.81 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 4.1% 2.2% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.119N P=0.564N P=0.268N P=0.280N |(e) (e) (e) (e) | |POLY 3 | P=0.100N P=0.527N P=0.241N P=0.252N |(e) (e) (e) (e) | |POLY 1.5 | P=0.100N P=0.516N P=0.239N P=0.246N |(e) (e) (e) (e) | |POLY 6 | P=0.100N P=0.539N P=0.245N P=0.260N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.119N P=0.564N (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.101N P=0.500N P=0.247N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 18/49 (37%) 13/50 (26%) 11/50 (22%) |17/50 (34%) 19/50 (38%) 10/49 (20%) 19/50 (38%) | |POLY-3 RATE (b) | 17/49.64 18/47.53 13/48.32 11/48.20 |17/45.93 19/49.18 10/47.37 19/48.11 | |POLY-3 PERCENT (g) | 34.3% 37.9% 26.9% 22.8% |37.0% 38.6% 21.1% 39.5% | |TERMINAL (d) | 16/48 (33%) 13/40 (33%) 10/42 (24%) 6/40 (15%) |12/40 (30%) 15/45 (33%) 7/43 (16%) 13/40 (33%) | |FIRST INCIDENCE | 397 418 689 447 |9 600 618 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.156N P=0.292 P=0.403N P=0.273N |P=0.454 P=0.573 P=0.073N P=0.432 | |POLY 3 | P=0.076N P=0.437 P=0.286N P=0.152N |P=0.527 P=0.519 P=0.070N P=0.486 | |POLY 1.5 | P=0.071N P=0.451 P=0.275N P=0.144N |P=0.527 P=0.497 P=0.074N P=0.480 | |POLY 6 | P=0.081N P=0.416 P=0.298N P=0.163N |P=0.513 P=0.534 P=0.070N P=0.476 | |LOGISTIC REGRESSION| P=0.040N* P=0.555N P=0.250N P=0.061N |P=0.460 P=0.403 P=0.106N P=0.388 | |COCH-ARM / FISHERS | P=0.065N P=0.470 P=0.257N P=0.133N |P=0.486 P=0.418 P=0.098N P=0.418 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/49 (10%) 3/50 (6%) 6/50 (12%) |8/50 (16%) 7/50 (14%) 2/49 (4%) 4/50 (8%) | |POLY-3 RATE (b) | 3/49.64 5/46.71 3/48.69 6/47.38 |8/47.58 7/49.55 2/46.87 4/47.42 | |POLY-3 PERCENT (g) | 6.0% 10.7% 6.2% 12.7% |16.8% 14.1% 4.3% 8.4% | |TERMINAL (d) | 2/48 (4%) 1/40 (3%) 0/42 (0%) 2/40 (5%) |2/40 (5%) 3/45 (7%) 1/43 (2%) 0/40 (0%) | |FIRST INCIDENCE | 397 419 616 456 |242 413 717 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.208 P=0.307 P=0.630 P=0.199 |P=0.097N P=0.432N P=0.046N* P=0.184N | |POLY 3 | P=0.219 P=0.324 P=0.653 P=0.220 |P=0.090N P=0.466N P=0.048N* P=0.179N | |POLY 1.5 | P=0.226 P=0.333 P=0.656 P=0.229 |P=0.087N P=0.473N P=0.047N* P=0.174N | |POLY 6 | P=0.210 P=0.315 P=0.649 P=0.211 |P=0.094N P=0.458N P=0.049N* P=0.185N | |LOGISTIC REGRESSION| P=0.320 P=0.618 P=0.662N P=0.399 |P=0.159N P=0.405 P=0.157N P=0.342N | |COCH-ARM / FISHERS | P=0.237 P=0.346 P=0.661N P=0.243 |P=0.088N P=0.500N P=0.049N* P=0.178N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 3/49 (6%) 3/50 (6%) 5/50 (10%) |8/50 (16%) 7/50 (14%) 12/49 (24%) 13/50 (26%) | |POLY-3 RATE (b) | 6/48.80 3/44.79 3/48.06 5/45.81 |8/43.96 7/47.89 12/47.19 13/45.29 | |POLY-3 PERCENT (g) | 12.3% 6.7% 6.2% 10.9% |18.2% 14.6% 25.4% 28.7% | |TERMINAL (d) | 6/48 (13%) 3/40 (8%) 2/42 (5%) 5/40 (13%) |8/40 (20%) 7/45 (16%) 11/43 (26%) 13/40 (33%) | |FIRST INCIDENCE | 727 (T) 727 (T) 710 727 (T) |733 (T) 733 (T) 625 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.527 P=0.339N P=0.311N P=0.626 |P=0.058 P=0.401N P=0.284 P=0.156 | |POLY 3 | P=0.527N P=0.287N P=0.250N P=0.544N |P=0.074 P=0.429N P=0.282 P=0.178 | |POLY 1.5 | P=0.520N P=0.273N P=0.247N P=0.525N |P=0.079 P=0.440N P=0.270 P=0.184 | |POLY 6 | P=0.538N P=0.303N P=0.257N P=0.569N |P=0.067 P=0.423N P=0.289 P=0.166 | |LOGISTIC REGRESSION| P=0.543 P=0.339N P=0.263N P=0.626 |P=0.063 P=0.401N P=0.276 P=0.156 | |COCH-ARM / FISHERS | P=0.513N P=0.254N P=0.243N P=0.500N |P=0.075 P=0.500N P=0.212 P=0.163 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 0/44.79 0/47.99 2/45.98 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 1/40 (3%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- 682 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.203 |(e) (e) (e) (e) | |POLY 3 | P=0.045 * (e) (e) P=0.224 |(e) (e) (e) (e) | |POLY 1.5 | P=0.045 * (e) (e) P=0.230 |(e) (e) (e) (e) | |POLY 6 | P=0.044 * (e) (e) P=0.217 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.047 * (e) (e) P=0.240 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.047 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/49.64 0/44.79 2/48.66 0/45.81 |1/43.96 1/47.89 0/47.49 2/46.38 | |POLY-3 PERCENT (g) | 2.0% 0.0% 4.1% 0.0% |2.3% 2.1% 0.0% 4.3% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |1/40 (3%) 1/45 (2%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 397 --- 616 --- |733 (T) 733 (T) --- 523 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.467N P=0.500N P=0.500 P=0.500N |P=0.363 P=0.735N P=0.486N P=0.510 | |POLY 3 | P=0.472N P=0.520N P=0.493 P=0.516N |P=0.374 P=0.741N P=0.485N P=0.519 | |POLY 1.5 | P=0.466N P=0.514N P=0.496 P=0.510N |P=0.374 P=0.744N P=0.486N P=0.518 | |POLY 6 | P=0.480N P=0.527N P=0.490 P=0.524N |P=0.372 P=0.740N P=0.485N P=0.517 | |LOGISTIC REGRESSION| P=0.431N (e) P=0.500 (e) |P=0.325 P=0.735N (e) P=0.449 | |COCH-ARM / FISHERS | P=0.459N P=0.505N P=0.500 P=0.500N |P=0.366 P=0.753N P=0.500N P=0.500 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperkeratosis Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.80 0/44.79 0/47.99 2/47.25 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 2.1% 0.0% 0.0% 4.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/48 (2%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- --- 447 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.240 P=0.536N P=0.527N P=0.479 |(e) (e) (e) (e) | |POLY 3 | P=0.250 P=0.517N P=0.503N P=0.489 |(e) (e) (e) (e) | |POLY 1.5 | P=0.250 P=0.512N P=0.502N P=0.494 |(e) (e) (e) (e) | |POLY 6 | P=0.250 P=0.523N P=0.506N P=0.480 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.257 (e) (e) P=0.658 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.247 P=0.505N P=0.500N P=0.500 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.80 0/44.79 2/48.27 0/45.81 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 2.1% 0.0% 4.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/48 (2%) 0/40 (0%) 1/42 (2%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- 650 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.489N P=0.536N P=0.469 P=0.536N |(e) (e) (e) (e) | |POLY 3 | P=0.469N P=0.517N P=0.496 P=0.513N |(e) (e) (e) (e) | |POLY 1.5 | P=0.464N P=0.512N P=0.498 P=0.507N |(e) (e) (e) (e) | |POLY 6 | P=0.476N P=0.523N P=0.493 P=0.520N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.454N (e) P=0.504 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.459N P=0.505N P=0.500 P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 2/50 (4%) 2/50 (4%) |3/50 (6%) 3/50 (6%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/48.80 0/44.79 2/48.38 2/45.98 |3/44.00 3/47.89 1/47.49 2/46.38 | |POLY-3 PERCENT (g) | 2.1% 0.0% 4.1% 4.4% |6.8% 6.3% 2.1% 4.3% | |TERMINAL (d) | 1/48 (2%) 0/40 (0%) 1/42 (2%) 1/40 (3%) |2/40 (5%) 3/45 (7%) 1/43 (2%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- 616 682 |722 733 (T) 733 (T) 523 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.218 P=0.536N P=0.469 P=0.440 |P=0.353N P=0.608N P=0.284N P=0.494N | |POLY 3 | P=0.239 P=0.517N P=0.497 P=0.479 |P=0.333N P=0.622N P=0.279N P=0.476N | |POLY 1.5 | P=0.243 P=0.512N P=0.499 P=0.488 |P=0.333N P=0.628N P=0.282N P=0.477N | |POLY 6 | P=0.232 P=0.523N P=0.494 P=0.468 |P=0.335N P=0.620N P=0.279N P=0.478N | |LOGISTIC REGRESSION| P=0.257 (e) P=0.504 P=0.495 |P=0.352N P=0.619N P=0.279N P=0.522N | |COCH-ARM / FISHERS | P=0.248 P=0.505N P=0.500 P=0.500 |P=0.344N P=0.661N P=0.309N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 2/48.50 0/45.81 |1/44.92 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.1% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 616 --- |243 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.578 (e) P=0.233 (e) |P=0.300N P=0.488N P=0.488N P=0.488N | |POLY 3 | P=0.570 (e) P=0.236 (e) |P=0.311N P=0.487N P=0.489N P=0.498N | |POLY 1.5 | P=0.582 (e) P=0.237 (e) |P=0.311N P=0.489N P=0.490N P=0.496N | |POLY 6 | P=0.554 (e) P=0.234 (e) |P=0.309N P=0.486N P=0.489N P=0.502N | |LOGISTIC REGRESSION| P=0.610 (e) P=0.233 (e) |P=0.594N P=0.915N P=0.924N P=0.811N | |COCH-ARM / FISHERS | P=0.596 (e) P=0.247 (e) |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Stomach, Glandular: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/48.80 0/45.14 0/47.99 1/45.81 |0/43.96 0/47.89 0/47.49 0/45.29 | |POLY-3 PERCENT (g) | 4.1% 0.0% 0.0% 2.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/48 (4%) 0/40 (0%) 0/42 (0%) 1/40 (3%) |0/40 (0%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 727 (T) --- --- 727 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.499N P=0.280N P=0.268N P=0.564N |(e) (e) (e) (e) | |POLY 3 | P=0.448N P=0.255N P=0.241N P=0.522N |(e) (e) (e) (e) | |POLY 1.5 | P=0.453N P=0.248N P=0.239N P=0.513N |(e) (e) (e) (e) | |POLY 6 | P=0.443N P=0.264N P=0.245N P=0.535N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.499N (e) (e) P=0.564N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.462N P=0.247N P=0.247N P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) 4/50 (8%) 4/50 (8%) | | |POLY-3 RATE (b) | 4/48.80 0/45.14 4/48.53 4/46.06 | | |POLY-3 PERCENT (g) | 8.2% 0.0% 8.2% 8.7% | | |TERMINAL (d) | 4/48 (8%) 0/40 (0%) 2/42 (5%) 3/40 (8%) | | |FIRST INCIDENCE | 727 (T) --- 616 661 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.286 P=0.089N P=0.583 P=0.545 | | |POLY 3 | P=0.338 P=0.071N P=0.640 P=0.611 | | |POLY 1.5 | P=0.341 P=0.067N P=0.641 P=0.624 | | |POLY 6 | P=0.332 P=0.077N P=0.636 P=0.593 | | |LOGISTIC REGRESSION| P=0.340 (e) P=0.639N P=0.612 | | |COCH-ARM / FISHERS | P=0.344 P=0.059N P=0.643N P=0.643N | | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 41/50 (82%) 39/48 (81%) 32/48 (67%) 41/46 (89%) |26/47 (55%) 33/49 (67%) 24/48 (50%) 19/50 (38%) | |POLY-3 RATE (b) | 41/49.16 39/48.00 32/48.00 41/44.38 |26/46.00 33/49.00 24/45.96 19/49.72 | |POLY-3 PERCENT (g) | 83.4% 81.3% 66.7% 92.4% |56.5% 67.4% 52.2% 38.2% | |TERMINAL (d) | 40/48 (83%) 30/39 (77%) 24/40 (60%) 36/37 (97%) |19/39 (49%) 29/45 (64%) 21/41 (51%) 10/40 (25%) | |FIRST INCIDENCE | 626 418 427 447 |242 413 645 264 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.078 P=0.172 P=0.347N P=0.008 ** |P=0.046N* P=0.353 P=0.336N P=0.130N | |POLY 3 | P=0.209 P=0.496N P=0.045N* P=0.149 |P=0.009N** P=0.192 P=0.419N P=0.055N | |POLY 1.5 | P=0.243 P=0.516N P=0.050N P=0.192 |P=0.008N** P=0.192 P=0.385N P=0.054N | |POLY 6 | P=0.162 P=0.484N P=0.043N* P=0.094 |P=0.010N* P=0.192 P=0.460N P=0.057N | |LOGISTIC REGRESSION| P=0.282 P=0.559N P=0.067N P=0.122 |P=0.012N* P=0.127 P=0.385N P=0.073N | |COCH-ARM / FISHERS | P=0.286 P=0.565N P=0.065N P=0.243 |P=0.012N* P=0.159 P=0.377N P=0.066N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/48 (2%) 0/48 (0%) 0/46 (0%) |11/47 (23%) 5/49 (10%) 16/48 (33%) 14/50 (28%) | |POLY-3 RATE (b) | 0/48.80 1/43.50 0/45.99 0/42.56 |11/42.19 5/47.03 16/46.27 14/45.29 | |POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 0.0% |26.1% 10.6% 34.6% 30.9% | |TERMINAL (d) | 0/48 (0%) 1/39 (3%) 0/40 (0%) 0/37 (0%) |11/39 (28%) 5/45 (11%) 14/41 (34%) 14/40 (35%) | |FIRST INCIDENCE | --- 727 (T) --- --- |733 (T) 733 (T) 618 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.600N P=0.459 (e) (e) |P=0.081 P=0.044N* P=0.228 P=0.343 | |POLY 3 | P=0.589N P=0.477 (e) (e) |P=0.104 P=0.051N P=0.263 P=0.396 | |POLY 1.5 | P=0.585N P=0.483 (e) (e) |P=0.115 P=0.054N P=0.254 P=0.410 | |POLY 6 | P=0.594N P=0.471 (e) (e) |P=0.091 P=0.050N P=0.267 P=0.373 | |LOGISTIC REGRESSION| (e) P=0.459 (e) (e) |P=0.101 P=0.044N* P=0.244 P=0.343 | |COCH-ARM / FISHERS | P=0.579N P=0.490 (e) (e) |P=0.123 P=0.071N P=0.199 P=0.388 | |=================================================================================================================================| Date: 07/06/01 EXPERIMENT: 56348 TEST: 04 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - CITRAL Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Thyroid Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/48 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/48.80 0/45.14 0/47.99 0/45.81 |2/43.11 0/47.89 0/47.49 0/44.92 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/48 (0%) 0/40 (0%) 0/42 (0%) 0/40 (0%) |2/40 (5%) 0/45 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |733 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.114N P=0.213N P=0.223N P=0.238N | |POLY 3 | (e) (e) (e) (e) |P=0.116N P=0.214N P=0.216N P=0.228N | |POLY 1.5 | (e) (e) (e) (e) |P=0.116N P=0.215N P=0.216N P=0.226N | |POLY 6 | (e) (e) (e) (e) |P=0.115N P=0.215N P=0.219N P=0.233N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.114N (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.113N P=0.237N P=0.237N P=0.242N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | UNTREAT 500 PPM 1000 PPM 2000 PPM |UNTREAT 500 PPM 1000 PPM 2000 PPM | | | CONTROL |CONTROL | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |43/50 (86%) 43/50 (86%) 44/50 (88%) 35/50 (70%) | |POLY-3 RATE (b) | |43/45.55 43/49.14 44/48.43 35/46.26 | |POLY-3 PERCENT (g) | |94.4% 87.5% 90.9% 75.7% | |TERMINAL (d) | |38/40 (95%) 40/45 (89%) 40/43 (93%) 33/40 (83%) | |FIRST INCIDENCE | |544 413 618 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.038N* P=0.152N P=0.379N P=0.035N* | |POLY 3 | |P=0.005N** P=0.200N P=0.390N P=0.008N** | |POLY 1.5 | |P=0.004N** P=0.246N P=0.414N P=0.008N** | |POLY 6 | |P=0.009N** P=0.202N P=0.429N P=0.013N* | |LOGISTIC REGRESSION| |P=0.005N** P=0.209N P=0.266N P=0.008N** | |COCH-ARM / FISHERS | |P=0.017N* P=0.613N P=0.500 P=0.045N* | |=================================================================================================================================| (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). --multipart-boundary Content-type: text/plain Range: bytes 283383-283383/283383 --multipart-boundary--