TDMS Study 93029-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR LEUKOMALACHITE GREEN DATE: 06/19/03 EXPERIMENT: 93029 TEST: 04 TIME: 07:10:49 TEST TYPE: CHRONIC PAGE: 1 CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93029 PATHOLOGIST: MISSING CAS: 129-73-7 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR LEUKOMALACHITE GREEN DATE: 06/19/03 EXPERIMENT: 93029 TEST: 04 TIME: 07:10:49 TEST TYPE: CHRONIC CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93029 PATHOLOGIST: MISSING CAS: 129-73-7 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF LEUKOMALACHITE GREEN =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Gland: Cortex, Subcapsular Hyperplasia Bone: Femur Fibrous Osteodystrophy Gallbladder: Mucosa Hyperplasia Focal Harderian Gland Hyperplasia Liver Infiltration Cellular Lymphocytic Lymph Node: Mandibular Hyperplasia Lymphoid Lymph Node: Renal Hyperplasia Lymphoid Ovary Cyst Thrombosis Skeletal Muscle Mineralization Spleen Hematopoietic Cell Proliferation Hyperplasia Lymphoid Urinary Bladder Inclusion Body Intracytoplasmic Infiltration Cellular Lymphocytic Vagina: Epithelium Hyperplasia =============================================================== Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/46 (7%) 1/48 (2%) 1/47 (2%) 1/47 (2%) | |POLY-3 RATE (b) | 3/42.55 1/46.24 1/43.97 1/44.65 | |POLY-3 PERCENT (g) | 7.1% 2.2% 2.3% 2.2% | |TERMINAL (d) | 2/37 (5%) 1/41 (2%) 1/39 (3%) 1/39 (3%) | |FIRST INCIDENCE | 639 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.244N P=0.276N P=0.295N P=0.293N | |POLY 3 | P=0.248N P=0.276N P=0.293N P=0.288N | |POLY 1.5 | P=0.247N P=0.278N P=0.293N P=0.288N | |POLY 6 | P=0.249N P=0.275N P=0.295N P=0.289N | |LOGISTIC REGRESSION| P=0.242N P=0.288N P=0.294N P=0.294N | |COCH-ARM / FISHERS | P=0.245N P=0.292N P=0.300N P=0.300N | |ORDER RESTRICTED | P=0.169N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/46 (4%) 0/48 (0%) 2/47 (4%) 0/47 (0%) | |POLY-3 RATE (b) | 2/42.21 0/46.24 2/43.97 0/44.65 | |POLY-3 PERCENT (g) | 4.7% 0.0% 4.6% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 2/39 (5%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.255N P=0.216N P=0.676N P=0.227N | |POLY 3 | P=0.259N P=0.217N P=0.679N P=0.225N | |POLY 1.5 | P=0.258N P=0.219N P=0.680N P=0.225N | |POLY 6 | P=0.260N P=0.216N P=0.679N P=0.224N | |LOGISTIC REGRESSION| P=0.255N (e) P=0.676N (e) | |COCH-ARM / FISHERS | P=0.258N P=0.237N P=0.683N P=0.242N | |ORDER RESTRICTED | P=0.107N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/46 (4%) 2/48 (4%) 2/47 (4%) 0/47 (0%) | |POLY-3 RATE (b) | 2/42.21 2/46.26 2/44.05 0/44.65 | |POLY-3 PERCENT (g) | 4.7% 4.3% 4.5% 0.0% | |TERMINAL (d) | 2/37 (5%) 1/41 (2%) 1/39 (3%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 729 714 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.156N P=0.654N P=0.675N P=0.227N | |POLY 3 | P=0.155N P=0.661N P=0.679N P=0.225N | |POLY 1.5 | P=0.155N P=0.663N P=0.679N P=0.225N | |POLY 6 | P=0.155N P=0.658N P=0.678N P=0.224N | |LOGISTIC REGRESSION| P=0.153N P=0.651N P=0.680N (e) | |COCH-ARM / FISHERS | P=0.159N P=0.675N P=0.683N P=0.242N | |ORDER RESTRICTED | P=0.177N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex, Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 42/46 (91%) 47/48 (98%) 46/47 (98%) 47/47 (100%) | |POLY-3 RATE (b) | 42/43.70 47/47.52 46/47.00 47/47.00 | |POLY-3 PERCENT (g) | 96.1% 98.9% 97.9% 100.0% | |TERMINAL (d) | 36/37 (97%) 41/41 (100%) 38/39 (97%) 39/39 (100%) | |FIRST INCIDENCE | 518 498 193 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.264 P=0.555 P=0.410 P=0.335 | |POLY 3 | P=0.192 P=0.419 P=0.553 P=0.262 | |POLY 1.5 | P=0.137 P=0.383 P=0.463 P=0.192 | |POLY 6 | P=0.255 P=0.415 P=0.623 P=0.324 | |LOGISTIC REGRESSION| P=0.068 P=0.443 P=0.226 P=0.150 | |COCH-ARM / FISHERS | P=0.036 * P=0.168 P=0.174 P=0.056 | |ORDER RESTRICTED | P=0.099 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/46 (9%) 1/48 (2%) 4/47 (9%) 6/46 (13%) | |POLY-3 RATE (b) | 4/43.50 1/46.34 4/45.04 6/45.12 | |POLY-3 PERCENT (g) | 9.2% 2.2% 8.9% 13.3% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 1/39 (3%) 2/39 (5%) | |FIRST INCIDENCE | 688 708 498 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155 P=0.154N P=0.619N P=0.409 | |POLY 3 | P=0.139 P=0.160N P=0.624N P=0.393 | |POLY 1.5 | P=0.137 P=0.161N P=0.626N P=0.387 | |POLY 6 | P=0.144 P=0.159N P=0.621N P=0.402 | |LOGISTIC REGRESSION| P=0.114 P=0.168N P=0.636N P=0.345 | |COCH-ARM / FISHERS | P=0.132 P=0.168N P=0.631N P=0.370 | |ORDER RESTRICTED | P=0.148 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Bone: Femur | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/47 (17%) 2/48 (4%) 5/47 (11%) 3/47 (6%) | |POLY-3 RATE (b) | 8/43.40 2/46.24 5/43.97 3/44.65 | |POLY-3 PERCENT (g) | 18.4% 4.3% 11.4% 6.7% | |TERMINAL (d) | 7/37 (19%) 2/41 (5%) 5/39 (13%) 3/39 (8%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.142N P=0.034N* P=0.246N P=0.087N | |POLY 3 | P=0.152N P=0.035N* P=0.266N P=0.089N | |POLY 1.5 | P=0.151N P=0.036N* P=0.266N P=0.089N | |POLY 6 | P=0.152N P=0.034N* P=0.268N P=0.089N | |LOGISTIC REGRESSION| P=0.142N P=0.036N* P=0.261N P=0.088N | |COCH-ARM / FISHERS | P=0.153N P=0.042N* P=0.276N P=0.099N | |ORDER RESTRICTED | P=0.048N* (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Bone: Sternum | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 3/48 (6%) 1/47 (2%) 5/47 (11%) | |POLY-3 RATE (b) | 1/43.21 3/46.24 1/43.97 5/44.68 | |POLY-3 PERCENT (g) | 2.3% 6.5% 2.3% 11.2% | |TERMINAL (d) | 1/37 (3%) 3/41 (7%) 1/39 (3%) 4/39 (10%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 724 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083 P=0.342 P=0.750N P=0.117 | |POLY 3 | P=0.082 P=0.330 P=0.757N P=0.109 | |POLY 1.5 | P=0.082 P=0.327 P=0.757N P=0.109 | |POLY 6 | P=0.082 P=0.332 P=0.757N P=0.110 | |LOGISTIC REGRESSION| P=0.085 P=0.342 P=0.750N P=0.115 | |COCH-ARM / FISHERS | P=0.079 P=0.316 P=0.753N P=0.102 | |ORDER RESTRICTED | P=0.051 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Bone: Sternum | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/47 (55%) 21/48 (44%) 19/47 (40%) 21/47 (45%) | |POLY-3 RATE (b) | 26/43.35 21/46.26 19/43.97 21/44.65 | |POLY-3 PERCENT (g) | 60.0% 45.4% 43.2% 47.0% | |TERMINAL (d) | 25/37 (68%) 20/41 (49%) 19/39 (49%) 21/39 (54%) | |FIRST INCIDENCE | 695 729 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.167N P=0.082N P=0.053N P=0.117N | |POLY 3 | P=0.200N P=0.119N P=0.084N P=0.155N | |POLY 1.5 | P=0.200N P=0.127N P=0.087N P=0.160N | |POLY 6 | P=0.199N P=0.111N P=0.083N P=0.151N | |LOGISTIC REGRESSION| P=0.145N P=0.079N P=0.066N P=0.100N | |COCH-ARM / FISHERS | P=0.223N P=0.178N P=0.108N P=0.205N | |ORDER RESTRICTED | P=0.126N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Brain: Cerebrum | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/47 (32%) 18/48 (38%) 21/47 (45%) 21/47 (45%) | |POLY-3 RATE (b) | 15/44.05 18/47.50 21/44.32 21/45.49 | |POLY-3 PERCENT (g) | 34.1% 37.9% 47.4% 46.2% | |TERMINAL (d) | 13/37 (35%) 15/41 (37%) 19/39 (49%) 19/39 (49%) | |FIRST INCIDENCE | 518 498 675 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.142 P=0.467 P=0.192 P=0.198 | |POLY 3 | P=0.121 P=0.435 P=0.144 P=0.170 | |POLY 1.5 | P=0.125 P=0.421 P=0.148 P=0.170 | |POLY 6 | P=0.115 P=0.448 P=0.139 P=0.167 | |LOGISTIC REGRESSION| P=0.122 P=0.371 P=0.156 P=0.162 | |COCH-ARM / FISHERS | P=0.113 P=0.361 P=0.144 P=0.144 | |ORDER RESTRICTED | P=0.173 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 44/45 (98%) 46/46 (100%) 41/44 (93%) 45/45 (100%) | |POLY-3 RATE (b) | 44/45.00 46/46.00 41/43.02 45/45.00 | |POLY-3 PERCENT (g) | 97.8% 100.0% 95.3% 100.0% | |TERMINAL (d) | 35/36 (97%) 40/40 (100%) 35/37 (95%) 38/38 (100%) | |FIRST INCIDENCE | 122 590 620 553 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.450N P=0.350N P=0.234N P=0.466N | |POLY 3 | P=0.477 P=0.496 P=0.480N P=0.500 | |POLY 1.5 | P=0.482 P=0.496 P=0.453N P=0.500 | |POLY 6 | P=0.477 P=0.496 P=0.484N P=0.500 | |LOGISTIC REGRESSION| P=0.616 (e) P=0.266N (e) | |COCH-ARM / FISHERS | P=0.518 P=0.495 P=0.300N P=0.500 | |ORDER RESTRICTED | P=0.320 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Eye: Bilateral, Lens | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/47 (9%) 5/48 (10%) 3/47 (6%) 7/47 (15%) | |POLY-3 RATE (b) | 4/44.84 5/46.74 3/44.10 7/46.53 | |POLY-3 PERCENT (g) | 8.9% 10.7% 6.8% 15.0% | |TERMINAL (d) | 0/37 (0%) 3/41 (7%) 2/39 (5%) 3/39 (8%) | |FIRST INCIDENCE | 225 590 700 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.240 P=0.547 P=0.488N P=0.296 | |POLY 3 | P=0.231 P=0.526 P=0.509N P=0.283 | |POLY 1.5 | P=0.228 P=0.525 P=0.504N P=0.279 | |POLY 6 | P=0.234 P=0.526 P=0.514N P=0.287 | |LOGISTIC REGRESSION| P=0.152 P=0.364 P=0.548N P=0.132 | |COCH-ARM / FISHERS | P=0.218 P=0.514 P=0.500N P=0.261 | |ORDER RESTRICTED | P=0.265 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Eye: Lens | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/47 (19%) 9/48 (19%) 7/47 (15%) 11/47 (23%) | |POLY-3 RATE (b) | 9/46.63 9/46.74 7/44.27 11/46.53 | |POLY-3 PERCENT (g) | 19.3% 19.3% 15.8% 23.6% | |TERMINAL (d) | 2/37 (5%) 7/41 (17%) 5/39 (13%) 7/39 (18%) | |FIRST INCIDENCE | 122 590 690 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.380 P=0.526N P=0.375N P=0.450 | |POLY 3 | P=0.346 P=0.600N P=0.437N P=0.399 | |POLY 1.5 | P=0.346 P=0.594N P=0.424N P=0.400 | |POLY 6 | P=0.345 P=0.597 P=0.450N P=0.398 | |LOGISTIC REGRESSION| P=0.275 P=0.443 P=0.453N P=0.246 | |COCH-ARM / FISHERS | P=0.347 P=0.584N P=0.392N P=0.401 | |ORDER RESTRICTED | P=0.401 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Gallbladder: Mucosa | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/44 (0%) 0/47 (0%) 0/44 (0%) 2/46 (4%) | |POLY-3 RATE (b) | 0/42.02 0/45.24 0/41.05 2/44.22 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 0/37 (0%) 0/40 (0%) 0/37 (0%) 2/39 (5%) | |FIRST INCIDENCE | --- --- --- 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.047 * (e) (e) P=0.250 | |POLY 3 | P=0.046 * (e) (e) P=0.249 | |POLY 1.5 | P=0.046 * (e) (e) P=0.249 | |POLY 6 | P=0.046 * (e) (e) P=0.248 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.250 | |COCH-ARM / FISHERS | P=0.047 * (e) (e) P=0.258 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 1/48 (2%) 1/47 (2%) 3/47 (6%) | |POLY-3 RATE (b) | 0/43.21 1/46.24 1/44.05 3/45.28 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.3% 6.6% | |TERMINAL (d) | 0/37 (0%) 1/41 (2%) 0/39 (0%) 1/39 (3%) | |FIRST INCIDENCE | --- 733 (T) 714 553 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062 P=0.520 P=0.510 P=0.137 | |POLY 3 | P=0.057 P=0.514 P=0.504 P=0.127 | |POLY 1.5 | P=0.057 P=0.512 P=0.504 P=0.126 | |POLY 6 | P=0.058 P=0.515 P=0.504 P=0.129 | |LOGISTIC REGRESSION| P=0.048 * P=0.520 P=0.502 P=0.096 | |COCH-ARM / FISHERS | P=0.054 P=0.505 P=0.500 P=0.121 | |ORDER RESTRICTED | P=0.042 * (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/47 (9%) 9/48 (19%) 8/47 (17%) 5/47 (11%) | |POLY-3 RATE (b) | 4/43.21 9/46.63 8/44.88 5/44.65 | |POLY-3 PERCENT (g) | 9.3% 19.3% 17.8% 11.2% | |TERMINAL (d) | 4/37 (11%) 7/41 (17%) 4/39 (10%) 5/39 (13%) | |FIRST INCIDENCE | 733 (T) 675 620 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.498N P=0.163 P=0.208 P=0.533 | |POLY 3 | P=0.496N P=0.146 P=0.195 P=0.521 | |POLY 1.5 | P=0.497N P=0.142 P=0.190 P=0.519 | |POLY 6 | P=0.494N P=0.152 P=0.203 P=0.523 | |LOGISTIC REGRESSION| P=0.509N P=0.142 P=0.181 P=0.533 | |COCH-ARM / FISHERS | P=0.519N P=0.124 P=0.177 P=0.500 | |ORDER RESTRICTED | P=0.289 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Intestine Small: Ileum | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/43 (2%) 1/47 (2%) 3/47 (6%) 1/43 (2%) | |POLY-3 RATE (b) | 1/41.15 1/45.26 3/43.97 1/42.53 | |POLY-3 PERCENT (g) | 2.4% 2.2% 6.8% 2.4% | |TERMINAL (d) | 1/37 (3%) 1/41 (2%) 3/39 (8%) 1/39 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.557 P=0.739N P=0.324 P=0.750N | |POLY 3 | P=0.560 P=0.739N P=0.329 P=0.753N | |POLY 1.5 | P=0.555 P=0.738N P=0.333 P=0.754N | |POLY 6 | P=0.566 P=0.740N P=0.325 P=0.751N | |LOGISTIC REGRESSION| P=0.557 P=0.739N P=0.324 P=0.750N | |COCH-ARM / FISHERS | P=0.542 P=0.730N P=0.343 P=0.753N | |ORDER RESTRICTED | P=0.452 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Intestine Small: Jejunum | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/43 (0%) 0/47 (0%) 2/47 (4%) 1/43 (2%) | |POLY-3 RATE (b) | 0/41.15 0/45.26 2/43.97 1/42.53 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 2.4% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 2/39 (5%) 1/39 (3%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.241 (e) P=0.250 P=0.511 | |POLY 3 | P=0.242 (e) P=0.252 P=0.507 | |POLY 1.5 | P=0.239 (e) P=0.254 P=0.505 | |POLY 6 | P=0.246 (e) P=0.249 P=0.508 | |LOGISTIC REGRESSION| (e) (e) P=0.250 P=0.511 | |COCH-ARM / FISHERS | P=0.229 (e) P=0.270 P=0.500 | |ORDER RESTRICTED | P=0.180 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 0/48 (0%) 1/47 (2%) 1/47 (2%) | |POLY-3 RATE (b) | 2/43.21 0/46.24 1/43.97 1/44.65 | |POLY-3 PERCENT (g) | 4.6% 0.0% 2.3% 2.2% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 1/39 (3%) 1/39 (3%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.508N P=0.216N P=0.482N P=0.482N | |POLY 3 | P=0.521N P=0.222N P=0.494N P=0.489N | |POLY 1.5 | P=0.520N P=0.224N P=0.494N P=0.489N | |POLY 6 | P=0.523N P=0.221N P=0.494N P=0.487N | |LOGISTIC REGRESSION| P=0.508N (e) P=0.482N P=0.482N | |COCH-ARM / FISHERS | P=0.517N P=0.242N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.258N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/47 (19%) 5/48 (10%) 15/47 (32%) 11/47 (23%) | |POLY-3 RATE (b) | 9/43.21 5/46.34 15/44.83 11/44.65 | |POLY-3 PERCENT (g) | 20.8% 10.8% 33.5% 24.6% | |TERMINAL (d) | 9/37 (24%) 4/41 (10%) 13/39 (33%) 11/39 (28%) | |FIRST INCIDENCE | 733 (T) 708 498 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.167 P=0.140N P=0.150 P=0.451 | |POLY 3 | P=0.153 P=0.155N P=0.137 P=0.433 | |POLY 1.5 | P=0.155 P=0.159N P=0.133 P=0.430 | |POLY 6 | P=0.152 P=0.150N P=0.141 P=0.436 | |LOGISTIC REGRESSION| P=0.158 P=0.143N P=0.126 P=0.451 | |COCH-ARM / FISHERS | P=0.149 P=0.181N P=0.118 P=0.401 | |ORDER RESTRICTED | P=0.099 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 2/48 (4%) 3/47 (6%) 1/47 (2%) | |POLY-3 RATE (b) | 1/43.21 2/46.24 3/43.97 1/44.65 | |POLY-3 PERCENT (g) | 2.3% 4.3% 6.8% 2.2% | |TERMINAL (d) | 1/37 (3%) 2/41 (5%) 3/39 (8%) 1/39 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.566N P=0.536 P=0.324 P=0.750N | |POLY 3 | P=0.566N P=0.524 P=0.312 P=0.753N | |POLY 1.5 | P=0.566N P=0.521 P=0.311 P=0.754N | |POLY 6 | P=0.565N P=0.526 P=0.311 P=0.752N | |LOGISTIC REGRESSION| P=0.566N P=0.536 P=0.324 P=0.750N | |COCH-ARM / FISHERS | P=0.577N P=0.508 P=0.308 P=0.753N | |ORDER RESTRICTED | P=0.466N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 1/48 (2%) 0/47 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/43.35 1/46.41 0/43.97 0/44.65 | |POLY-3 PERCENT (g) | 4.6% 2.2% 0.0% 0.0% | |TERMINAL (d) | 1/37 (3%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 695 690 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.098N P=0.464N P=0.231N P=0.226N | |POLY 3 | P=0.102N P=0.476N P=0.234N P=0.231N | |POLY 1.5 | P=0.102N P=0.479N P=0.234N P=0.231N | |POLY 6 | P=0.103N P=0.474N P=0.234N P=0.230N | |LOGISTIC REGRESSION| P=0.102N P=0.497N P=0.235N P=0.234N | |COCH-ARM / FISHERS | P=0.101N P=0.492N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 2/48 (4%) 1/47 (2%) 3/47 (6%) | |POLY-3 RATE (b) | 1/43.34 2/46.41 1/44.10 3/45.55 | |POLY-3 PERCENT (g) | 2.3% 4.3% 2.3% 6.6% | |TERMINAL (d) | 0/37 (0%) 1/41 (2%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 700 690 700 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263 P=0.539 P=0.751N P=0.343 | |POLY 3 | P=0.252 P=0.524 P=0.757N P=0.323 | |POLY 1.5 | P=0.250 P=0.521 P=0.757N P=0.321 | |POLY 6 | P=0.253 P=0.526 P=0.757N P=0.326 | |LOGISTIC REGRESSION| P=0.206 P=0.505 P=0.762 P=0.236 | |COCH-ARM / FISHERS | P=0.238 P=0.508 P=0.753N P=0.308 | |ORDER RESTRICTED | P=0.240 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 2/48 (4%) 0/47 (0%) 3/47 (6%) | |POLY-3 RATE (b) | 1/43.38 2/46.34 0/43.97 3/44.65 | |POLY-3 PERCENT (g) | 2.3% 4.3% 0.0% 6.7% | |TERMINAL (d) | 0/37 (0%) 1/41 (2%) 0/39 (0%) 3/39 (8%) | |FIRST INCIDENCE | 688 709 --- 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.259 P=0.537 P=0.495N P=0.325 | |POLY 3 | P=0.250 P=0.523 P=0.497N P=0.316 | |POLY 1.5 | P=0.251 P=0.521 P=0.497N P=0.316 | |POLY 6 | P=0.250 P=0.525 P=0.498N P=0.316 | |LOGISTIC REGRESSION| P=0.250 P=0.507 P=0.503N P=0.314 | |COCH-ARM / FISHERS | P=0.246 P=0.508 P=0.500N P=0.308 | |ORDER RESTRICTED | P=0.193 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 2/48 (4%) 3/47 (6%) 3/47 (6%) | |POLY-3 RATE (b) | 2/43.35 2/46.56 3/44.53 3/45.52 | |POLY-3 PERCENT (g) | 4.6% 4.3% 6.7% 6.6% | |TERMINAL (d) | 1/37 (3%) 0/41 (0%) 1/39 (3%) 0/39 (0%) | |FIRST INCIDENCE | 695 675 620 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.382 P=0.655N P=0.518 P=0.526 | |POLY 3 | P=0.382 P=0.668N P=0.512 P=0.522 | |POLY 1.5 | P=0.378 P=0.671N P=0.510 P=0.518 | |POLY 6 | P=0.386 P=0.664N P=0.515 P=0.528 | |LOGISTIC REGRESSION| P=0.330 P=0.697 P=0.496 P=0.461 | |COCH-ARM / FISHERS | P=0.364 P=0.684N P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.514 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/47 (17%) 2/48 (4%) 2/47 (4%) 8/47 (17%) | |POLY-3 RATE (b) | 8/43.40 2/46.24 2/43.97 8/44.65 | |POLY-3 PERCENT (g) | 18.4% 4.3% 4.6% 17.9% | |TERMINAL (d) | 7/37 (19%) 2/41 (5%) 2/39 (5%) 8/39 (21%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.368 P=0.034N* P=0.041N* P=0.566N | |POLY 3 | P=0.345 P=0.035N* P=0.042N* P=0.584N | |POLY 1.5 | P=0.347 P=0.036N* P=0.042N* P=0.584N | |POLY 6 | P=0.343 P=0.034N* P=0.042N* P=0.584N | |LOGISTIC REGRESSION| P=0.368 P=0.036N* P=0.044N* P=0.572N | |COCH-ARM / FISHERS | P=0.351 P=0.042N* P=0.045N* P=0.608N | |ORDER RESTRICTED | P=0.116N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Inflammation Focal Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/47 (32%) 13/48 (27%) 16/47 (34%) 11/47 (23%) | |POLY-3 RATE (b) | 15/43.21 13/46.24 16/43.97 11/44.96 | |POLY-3 PERCENT (g) | 34.7% 28.1% 36.4% 24.5% | |TERMINAL (d) | 15/37 (41%) 13/41 (32%) 16/39 (41%) 10/39 (26%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.225N P=0.284N P=0.575 P=0.193N | |POLY 3 | P=0.234N P=0.329N P=0.524 P=0.206N | |POLY 1.5 | P=0.239N P=0.338N P=0.523 P=0.212N | |POLY 6 | P=0.227N P=0.320N P=0.525 P=0.197N | |LOGISTIC REGRESSION| P=0.221N P=0.284N P=0.575 P=0.203N | |COCH-ARM / FISHERS | P=0.262N P=0.385N P=0.500 P=0.245N | |ORDER RESTRICTED | P=0.238N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/47 (21%) 12/48 (25%) 9/47 (19%) 9/47 (19%) | |POLY-3 RATE (b) | 10/43.21 12/46.93 9/43.97 9/44.65 | |POLY-3 PERCENT (g) | 23.1% 25.6% 20.5% 20.2% | |TERMINAL (d) | 10/37 (27%) 11/41 (27%) 9/39 (23%) 9/39 (23%) | |FIRST INCIDENCE | 733 (T) 498 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.327N P=0.511 P=0.448N P=0.448N | |POLY 3 | P=0.344N P=0.491 P=0.483N P=0.468N | |POLY 1.5 | P=0.343N P=0.478 P=0.484N P=0.471N | |POLY 6 | P=0.345N P=0.504 P=0.483N P=0.464N | |LOGISTIC REGRESSION| P=0.340N P=0.464 P=0.448N P=0.448N | |COCH-ARM / FISHERS | P=0.358N P=0.426 P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.502N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 1/48 (2%) 0/47 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/43.21 1/46.34 0/43.97 0/44.65 | |POLY-3 PERCENT (g) | 4.6% 2.2% 0.0% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 708 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.097N P=0.459N P=0.227N P=0.227N | |POLY 3 | P=0.102N P=0.476N P=0.233N P=0.230N | |POLY 1.5 | P=0.102N P=0.478N P=0.233N P=0.230N | |POLY 6 | P=0.103N P=0.473N P=0.233N P=0.229N | |LOGISTIC REGRESSION| P=0.099N P=0.477N (e) (e) | |COCH-ARM / FISHERS | P=0.101N P=0.492N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/47 (6%) 1/48 (2%) 1/47 (2%) 1/47 (2%) | |POLY-3 RATE (b) | 3/43.21 1/46.24 1/43.97 1/44.65 | |POLY-3 PERCENT (g) | 6.9% 2.2% 2.3% 2.2% | |TERMINAL (d) | 3/37 (8%) 1/41 (2%) 1/39 (3%) 1/39 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.241N P=0.269N P=0.286N P=0.286N | |POLY 3 | P=0.252N P=0.281N P=0.299N P=0.294N | |POLY 1.5 | P=0.252N P=0.284N P=0.299N P=0.295N | |POLY 6 | P=0.253N P=0.279N P=0.299N P=0.292N | |LOGISTIC REGRESSION| P=0.241N P=0.269N P=0.286N P=0.286N | |COCH-ARM / FISHERS | P=0.250N P=0.301N P=0.308N P=0.308N | |ORDER RESTRICTED | P=0.174N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 2/48 (4%) 0/47 (0%) 2/47 (4%) | |POLY-3 RATE (b) | 1/43.21 2/46.24 0/43.97 2/44.65 | |POLY-3 PERCENT (g) | 2.3% 4.3% 0.0% 4.5% | |TERMINAL (d) | 1/37 (3%) 2/41 (5%) 0/39 (0%) 2/39 (5%) | |FIRST INCIDENCE | 733 (T) 733 (T) --- 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.486 P=0.536 P=0.489N P=0.518 | |POLY 3 | P=0.485 P=0.524 P=0.496N P=0.511 | |POLY 1.5 | P=0.485 P=0.521 P=0.497N P=0.511 | |POLY 6 | P=0.485 P=0.526 P=0.496N P=0.513 | |LOGISTIC REGRESSION| P=0.486 P=0.536 (e) P=0.518 | |COCH-ARM / FISHERS | P=0.477 P=0.508 P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.421 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/47 (28%) 7/48 (15%) 9/47 (19%) 12/47 (26%) | |POLY-3 RATE (b) | 13/43.89 7/46.34 9/44.53 12/45.02 | |POLY-3 PERCENT (g) | 29.6% 15.1% 20.2% 26.7% | |TERMINAL (d) | 10/37 (27%) 6/41 (15%) 7/39 (18%) 10/39 (26%) | |FIRST INCIDENCE | 639 708 620 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.495 P=0.072N P=0.209N P=0.443N | |POLY 3 | P=0.472 P=0.079N P=0.219N P=0.470N | |POLY 1.5 | P=0.473 P=0.079N P=0.219N P=0.469N | |POLY 6 | P=0.471 P=0.079N P=0.221N P=0.473N | |LOGISTIC REGRESSION| P=0.479 P=0.079N P=0.221N P=0.468N | |COCH-ARM / FISHERS | P=0.463 P=0.095N P=0.233N P=0.500N | |ORDER RESTRICTED | P=0.248N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lung | | Leukocytosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 2/48 (4%) 0/47 (0%) 1/47 (2%) | |POLY-3 RATE (b) | 0/43.21 2/46.94 0/43.97 1/45.14 | |POLY-3 PERCENT (g) | 0.0% 4.3% 0.0% 2.2% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | --- 590 --- 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.555 P=0.255 (e) P=0.504 | |POLY 3 | P=0.575 P=0.256 (e) P=0.509 | |POLY 1.5 | P=0.572 P=0.253 (e) P=0.507 | |POLY 6 | P=0.579 P=0.260 (e) P=0.511 | |LOGISTIC REGRESSION| P=0.490 P=0.170 (e) P=0.419 | |COCH-ARM / FISHERS | P=0.558 P=0.253 (e) P=0.500 | |ORDER RESTRICTED | P=0.333 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/44 (2%) 3/47 (6%) 8/45 (18%) 2/45 (4%) | |POLY-3 RATE (b) | 1/41.50 3/45.24 8/41.97 2/44.00 | |POLY-3 PERCENT (g) | 2.4% 6.6% 19.1% 4.6% | |TERMINAL (d) | 0/36 (0%) 3/40 (8%) 8/37 (22%) 2/39 (5%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.409 P=0.339 P=0.020 * P=0.519 | |POLY 3 | P=0.414 P=0.337 P=0.016 * P=0.520 | |POLY 1.5 | P=0.408 P=0.337 P=0.016 * P=0.518 | |POLY 6 | P=0.421 P=0.337 P=0.015 * P=0.523 | |LOGISTIC REGRESSION| P=0.411 P=0.333 P=0.018 * P=0.506 | |COCH-ARM / FISHERS | P=0.386 P=0.334 P=0.016 * P=0.509 | |ORDER RESTRICTED | P=0.087 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/44 (11%) 2/47 (4%) 3/45 (7%) 6/45 (13%) | |POLY-3 RATE (b) | 5/41.51 2/45.93 3/41.97 6/44.00 | |POLY-3 PERCENT (g) | 12.1% 4.4% 7.2% 13.6% | |TERMINAL (d) | 3/36 (8%) 1/40 (3%) 3/37 (8%) 6/39 (15%) | |FIRST INCIDENCE | 682 498 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309 P=0.189N P=0.347N P=0.547 | |POLY 3 | P=0.291 P=0.177N P=0.350N P=0.541 | |POLY 1.5 | P=0.290 P=0.179N P=0.346N P=0.536 | |POLY 6 | P=0.291 P=0.175N P=0.354N P=0.545 | |LOGISTIC REGRESSION| P=0.284 P=0.211N P=0.347N P=0.548 | |COCH-ARM / FISHERS | P=0.286 P=0.191N P=0.344N P=0.516 | |ORDER RESTRICTED | P=0.278 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/44 (0%) 0/47 (0%) 2/45 (4%) 1/45 (2%) | |POLY-3 RATE (b) | 0/41.31 0/45.24 2/41.97 1/44.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 2.3% | |TERMINAL (d) | 0/36 (0%) 0/40 (0%) 2/37 (5%) 1/39 (3%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.247 (e) P=0.244 P=0.516 | |POLY 3 | P=0.250 (e) P=0.241 P=0.513 | |POLY 1.5 | P=0.247 (e) P=0.242 P=0.511 | |POLY 6 | P=0.254 (e) P=0.240 P=0.515 | |LOGISTIC REGRESSION| (e) (e) P=0.244 P=0.516 | |COCH-ARM / FISHERS | P=0.237 (e) P=0.253 P=0.506 | |ORDER RESTRICTED | P=0.171 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/44 (5%) 0/47 (0%) 0/45 (0%) 0/45 (0%) | |POLY-3 RATE (b) | 2/41.51 0/45.24 0/41.97 0/44.00 | |POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/36 (0%) 0/40 (0%) 0/37 (0%) 0/39 (0%) | |FIRST INCIDENCE | 682 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.124N P=0.227N P=0.239N P=0.237N | |POLY 3 | P=0.123N P=0.218N P=0.234N P=0.224N | |POLY 1.5 | P=0.122N P=0.218N P=0.233N P=0.226N | |POLY 6 | P=0.123N P=0.218N P=0.236N P=0.223N | |LOGISTIC REGRESSION| P=0.122N P=0.226N P=0.232N P=0.237N | |COCH-ARM / FISHERS | P=0.121N P=0.231N P=0.242N P=0.242N | |ORDER RESTRICTED | P=0.025N* (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 2/2 (100%) 1/1 (100%) 3/3 (100%) | |POLY-3 RATE (b) | 1/1.00 2/2.00 1/1.00 3/3.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 1/1 (100%) 1/1 (100%) 1/1 (100%) 3/3 (100%) | |FIRST INCIDENCE | 733 (T) 708 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/46 (2%) 1/48 (2%) 2/47 (4%) 0/44 (0%) | |POLY-3 RATE (b) | 1/43.18 1/46.24 2/43.97 0/43.49 | |POLY-3 PERCENT (g) | 2.3% 2.2% 4.6% 0.0% | |TERMINAL (d) | 1/37 (3%) 1/41 (2%) 2/39 (5%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.361N P=0.739N P=0.518 P=0.489N | |POLY 3 | P=0.368N P=0.745N P=0.506 P=0.499N | |POLY 1.5 | P=0.372N P=0.746N P=0.507 P=0.501N | |POLY 6 | P=0.362N P=0.744N P=0.506 P=0.495N | |LOGISTIC REGRESSION| P=0.361N P=0.739N P=0.518 (e) | |COCH-ARM / FISHERS | P=0.382N P=0.742N P=0.508 P=0.511N | |ORDER RESTRICTED | P=0.281N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 42/46 (91%) 45/48 (94%) 44/47 (94%) 41/44 (93%) | |POLY-3 RATE (b) | 42/44.08 45/47.52 44/45.57 41/43.94 | |POLY-3 PERCENT (g) | 95.3% 94.7% 96.6% 93.3% | |TERMINAL (d) | 37/37 (100%) 39/41 (95%) 39/39 (100%) 37/39 (95%) | |FIRST INCIDENCE | 639 498 498 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.239N P=0.460N P=0.616N P=0.261N | |POLY 3 | P=0.443N P=0.646N P=0.600 P=0.525N | |POLY 1.5 | P=0.511N P=0.678N P=0.564 P=0.593N | |POLY 6 | P=0.363N P=0.610N P=0.660 P=0.447N | |LOGISTIC REGRESSION| P=0.450N P=0.628 P=0.443 P=0.427N | |COCH-ARM / FISHERS | P=0.476 P=0.476 P=0.488 P=0.525 | |ORDER RESTRICTED | P=0.493N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/46 (46%) 19/48 (40%) 19/47 (40%) 13/44 (30%) | |POLY-3 RATE (b) | 21/43.55 19/47.19 19/44.66 13/43.55 | |POLY-3 PERCENT (g) | 48.2% 40.3% 42.5% 29.9% | |TERMINAL (d) | 18/37 (49%) 16/41 (39%) 16/39 (41%) 12/39 (31%) | |FIRST INCIDENCE | 682 498 620 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.049N* P=0.275N P=0.349N P=0.048N* | |POLY 3 | P=0.060N P=0.291N P=0.374N P=0.060N | |POLY 1.5 | P=0.065N P=0.304N P=0.376N P=0.066N | |POLY 6 | P=0.055N P=0.277N P=0.367N P=0.054N | |LOGISTIC REGRESSION| P=0.062N P=0.320N P=0.387N P=0.049N* | |COCH-ARM / FISHERS | P=0.079N P=0.350N P=0.382N P=0.087N | |ORDER RESTRICTED | P=0.061N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/46 (9%) 2/48 (4%) 2/47 (4%) 2/44 (5%) | |POLY-3 RATE (b) | 4/43.37 2/46.24 2/43.97 2/43.49 | |POLY-3 PERCENT (g) | 9.2% 4.3% 4.6% 4.6% | |TERMINAL (d) | 3/37 (8%) 2/41 (5%) 2/39 (5%) 2/39 (5%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.290N P=0.296N P=0.320N P=0.318N | |POLY 3 | P=0.311N P=0.308N P=0.331N P=0.336N | |POLY 1.5 | P=0.314N P=0.309N P=0.329N P=0.342N | |POLY 6 | P=0.306N P=0.307N P=0.333N P=0.329N | |LOGISTIC REGRESSION| P=0.299N P=0.307N P=0.328N P=0.342N | |COCH-ARM / FISHERS | P=0.319N P=0.318N P=0.328N P=0.360N | |ORDER RESTRICTED | P=0.275N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/46 (7%) 0/48 (0%) 0/47 (0%) 0/44 (0%) | |POLY-3 RATE (b) | 3/43.35 0/46.24 0/43.97 0/43.49 | |POLY-3 PERCENT (g) | 6.9% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 688 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.106N P=0.116N P=0.114N | |POLY 3 | P=0.053N P=0.107N P=0.116N P=0.118N | |POLY 1.5 | P=0.053N P=0.108N P=0.115N P=0.120N | |POLY 6 | P=0.053N P=0.107N P=0.116N P=0.115N | |LOGISTIC REGRESSION| P=0.053N P=0.111N P=0.117N P=0.126N | |COCH-ARM / FISHERS | P=0.054N P=0.113N P=0.117N P=0.129N | |ORDER RESTRICTED | P=0.008N** (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Ovary: Bilateral | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/46 (15%) 3/48 (6%) 2/47 (4%) 3/44 (7%) | |POLY-3 RATE (b) | 7/43.37 3/46.24 2/43.97 3/43.49 | |POLY-3 PERCENT (g) | 16.1% 6.5% 4.6% 6.9% | |TERMINAL (d) | 6/37 (16%) 3/41 (7%) 2/39 (5%) 3/39 (8%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.126N P=0.123N P=0.072N P=0.141N | |POLY 3 | P=0.142N P=0.132N P=0.075N P=0.155N | |POLY 1.5 | P=0.144N P=0.133N P=0.074N P=0.161N | |POLY 6 | P=0.139N P=0.131N P=0.075N P=0.150N | |LOGISTIC REGRESSION| P=0.129N P=0.129N P=0.076N P=0.152N | |COCH-ARM / FISHERS | P=0.149N P=0.141N P=0.074N P=0.176N | |ORDER RESTRICTED | P=0.061N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/45 (0%) 2/48 (4%) 0/47 (0%) 0/45 (0%) | |POLY-3 RATE (b) | 0/42.31 2/46.24 0/43.97 0/44.00 | |POLY-3 PERCENT (g) | 0.0% 4.3% 0.0% 0.0% | |TERMINAL (d) | 0/37 (0%) 2/41 (5%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | --- 733 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.372N P=0.261 (e) (e) | |POLY 3 | P=0.370N P=0.257 (e) (e) | |POLY 1.5 | P=0.371N P=0.257 (e) (e) | |POLY 6 | P=0.368N P=0.258 (e) (e) | |LOGISTIC REGRESSION| (e) P=0.261 (e) (e) | |COCH-ARM / FISHERS | P=0.379N P=0.264 (e) (e) | |ORDER RESTRICTED | P=0.257N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/45 (2%) 1/48 (2%) 1/47 (2%) 2/45 (4%) | |POLY-3 RATE (b) | 1/42.31 1/46.24 1/43.97 2/44.00 | |POLY-3 PERCENT (g) | 2.4% 2.2% 2.3% 4.6% | |TERMINAL (d) | 1/37 (3%) 1/41 (2%) 1/39 (3%) 2/39 (5%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.355 P=0.739N P=0.750N P=0.518 | |POLY 3 | P=0.352 P=0.741N P=0.752N P=0.514 | |POLY 1.5 | P=0.350 P=0.741N P=0.751N P=0.511 | |POLY 6 | P=0.355 P=0.740N P=0.753N P=0.517 | |LOGISTIC REGRESSION| P=0.355 P=0.739N P=0.750N P=0.518 | |COCH-ARM / FISHERS | P=0.342 P=0.736N P=0.742N P=0.500 | |ORDER RESTRICTED | P=0.420 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/45 (16%) 9/48 (19%) 4/47 (9%) 6/45 (13%) | |POLY-3 RATE (b) | 7/42.50 9/46.41 4/43.97 6/44.06 | |POLY-3 PERCENT (g) | 16.5% 19.4% 9.1% 13.6% | |TERMINAL (d) | 6/37 (16%) 8/41 (20%) 4/39 (10%) 5/39 (13%) | |FIRST INCIDENCE | 682 690 733 (T) 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.282N P=0.478 P=0.236N P=0.459N | |POLY 3 | P=0.292N P=0.468 P=0.241N P=0.472N | |POLY 1.5 | P=0.296N P=0.465 P=0.238N P=0.478N | |POLY 6 | P=0.289N P=0.470 P=0.244N P=0.466N | |LOGISTIC REGRESSION| P=0.282N P=0.469 P=0.239N P=0.467N | |COCH-ARM / FISHERS | P=0.308N P=0.448 P=0.236N P=0.500N | |ORDER RESTRICTED | P=0.309N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/45 (2%) 2/48 (4%) 1/47 (2%) 2/45 (4%) | |POLY-3 RATE (b) | 1/42.31 2/46.56 1/43.97 2/44.37 | |POLY-3 PERCENT (g) | 2.4% 4.3% 2.3% 4.5% | |TERMINAL (d) | 1/37 (3%) 0/41 (0%) 1/39 (3%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 675 733 (T) 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.462 P=0.536 P=0.750N P=0.523 | |POLY 3 | P=0.459 P=0.533 P=0.752N P=0.517 | |POLY 1.5 | P=0.455 P=0.531 P=0.751N P=0.512 | |POLY 6 | P=0.465 P=0.537 P=0.753N P=0.522 | |LOGISTIC REGRESSION| P=0.428 P=0.513 P=0.750N P=0.477 | |COCH-ARM / FISHERS | P=0.443 P=0.524 P=0.742N P=0.500 | |ORDER RESTRICTED | P=0.465 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/41 (7%) 1/45 (2%) 3/44 (7%) 2/46 (4%) | |POLY-3 RATE (b) | 3/38.35 1/43.24 3/41.14 2/43.65 | |POLY-3 PERCENT (g) | 7.8% 2.3% 7.3% 4.6% | |TERMINAL (d) | 2/32 (6%) 1/38 (3%) 3/37 (8%) 2/38 (5%) | |FIRST INCIDENCE | 688 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.484N P=0.254N P=0.604N P=0.434N | |POLY 3 | P=0.495N P=0.263N P=0.630N P=0.441N | |POLY 1.5 | P=0.494N P=0.264N P=0.629N P=0.441N | |POLY 6 | P=0.496N P=0.261N P=0.630N P=0.440N | |LOGISTIC REGRESSION| P=0.488N P=0.264N P=0.628N P=0.439N | |COCH-ARM / FISHERS | P=0.494N P=0.274N P=0.628N P=0.445N | |ORDER RESTRICTED | P=0.415N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Acinus, Parotid Gland | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 3/48 (6%) 0/47 (0%) 1/47 (2%) | |POLY-3 RATE (b) | 1/43.40 3/46.56 0/43.97 1/44.71 | |POLY-3 PERCENT (g) | 2.3% 6.4% 0.0% 2.2% | |TERMINAL (d) | 0/37 (0%) 1/41 (2%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 682 675 --- 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.380N P=0.341 P=0.505N P=0.747N | |POLY 3 | P=0.381N P=0.331 P=0.497N P=0.754N | |POLY 1.5 | P=0.382N P=0.328 P=0.497N P=0.754N | |POLY 6 | P=0.381N P=0.334 P=0.498N P=0.754N | |LOGISTIC REGRESSION| P=0.395N P=0.297 P=0.505N P=0.761 | |COCH-ARM / FISHERS | P=0.390N P=0.316 P=0.500N P=0.753N | |ORDER RESTRICTED | P=0.277N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Acinus, Parotid Gland | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 3/47 (6%) 2/47 (4%) | |POLY-3 RATE (b) | 0/43.21 0/46.24 3/43.97 2/44.65 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.8% 4.5% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 3/39 (8%) 2/39 (5%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.093 (e) P=0.130 P=0.250 | |POLY 3 | P=0.092 (e) P=0.122 P=0.245 | |POLY 1.5 | P=0.093 (e) P=0.122 P=0.244 | |POLY 6 | P=0.092 (e) P=0.122 P=0.245 | |LOGISTIC REGRESSION| (e) (e) P=0.130 P=0.250 | |COCH-ARM / FISHERS | P=0.090 (e) P=0.121 P=0.247 | |ORDER RESTRICTED | P=0.083 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Parotid Gland | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/47 (19%) 9/48 (19%) 8/47 (17%) 11/47 (23%) | |POLY-3 RATE (b) | 9/43.40 9/46.94 8/43.97 11/45.20 | |POLY-3 PERCENT (g) | 20.7% 19.2% 18.2% 24.3% | |TERMINAL (d) | 8/37 (22%) 7/41 (17%) 8/39 (21%) 9/39 (23%) | |FIRST INCIDENCE | 682 590 733 (T) 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.362 P=0.514N P=0.456N P=0.453 | |POLY 3 | P=0.353 P=0.531N P=0.488N P=0.441 | |POLY 1.5 | P=0.353 P=0.541N P=0.487N P=0.435 | |POLY 6 | P=0.354 P=0.519N P=0.491N P=0.447 | |LOGISTIC REGRESSION| P=0.350 P=0.559N P=0.481N P=0.428 | |COCH-ARM / FISHERS | P=0.336 P=0.584N P=0.500N P=0.401 | |ORDER RESTRICTED | P=0.449 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Parotid Gland | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 0/48 (0%) 1/47 (2%) 0/47 (0%) | |POLY-3 RATE (b) | 2/43.21 0/46.24 1/44.05 0/44.65 | |POLY-3 PERCENT (g) | 4.6% 0.0% 2.3% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) --- 714 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.192N P=0.216N P=0.482N P=0.227N | |POLY 3 | P=0.203N P=0.222N P=0.493N P=0.230N | |POLY 1.5 | P=0.202N P=0.224N P=0.494N P=0.230N | |POLY 6 | P=0.204N P=0.221N P=0.493N P=0.229N | |LOGISTIC REGRESSION| P=0.196N (e) P=0.494N (e) | |COCH-ARM / FISHERS | P=0.200N P=0.242N P=0.500N P=0.247N | |ORDER RESTRICTED | P=0.069N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Sublingual Gland | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 2/47 (4%) 1/47 (2%) | |POLY-3 RATE (b) | 0/43.21 0/46.24 2/43.97 1/44.65 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 2.2% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 2/39 (5%) 1/39 (3%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.241 (e) P=0.250 P=0.511 | |POLY 3 | P=0.242 (e) P=0.241 P=0.507 | |POLY 1.5 | P=0.242 (e) P=0.241 P=0.506 | |POLY 6 | P=0.242 (e) P=0.241 P=0.507 | |LOGISTIC REGRESSION| (e) (e) P=0.250 P=0.511 | |COCH-ARM / FISHERS | P=0.236 (e) P=0.247 P=0.500 | |ORDER RESTRICTED | P=0.171 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Submandibular Gland | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/47 (70%) 30/48 (63%) 35/47 (74%) 31/47 (66%) | |POLY-3 RATE (b) | 33/43.72 30/47.79 35/45.72 31/45.52 | |POLY-3 PERCENT (g) | 75.5% 62.8% 76.6% 68.1% | |TERMINAL (d) | 30/37 (81%) 26/41 (63%) 30/39 (77%) 28/39 (72%) | |FIRST INCIDENCE | 682 498 498 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.424N P=0.142N P=0.558 P=0.275N | |POLY 3 | P=0.449N P=0.137N P=0.552 P=0.294N | |POLY 1.5 | P=0.449N P=0.165N P=0.513 P=0.311N | |POLY 6 | P=0.447N P=0.113N P=0.593 P=0.276N | |LOGISTIC REGRESSION| P=0.452N P=0.192N P=0.459 P=0.326N | |COCH-ARM / FISHERS | P=0.502N P=0.282N P=0.409 P=0.413N | |ORDER RESTRICTED | P=0.356N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Skeletal Muscle | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 0/47 (0%) 2/46 (4%) | |POLY-3 RATE (b) | 0/43.21 0/46.24 0/43.97 2/44.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 0/39 (0%) 0/39 (0%) | |FIRST INCIDENCE | --- --- --- 444 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.050 (e) (e) P=0.258 | |POLY 3 | P=0.043 * (e) (e) P=0.244 | |POLY 1.5 | P=0.043 * (e) (e) P=0.242 | |POLY 6 | P=0.043 * (e) (e) P=0.246 | |LOGISTIC REGRESSION| P=0.021 * (e) (e) P=0.136 | |COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.242 | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Spinal Cord: Thoracic, Axon | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/47 (26%) 11/48 (23%) 9/47 (19%) 14/47 (30%) | |POLY-3 RATE (b) | 12/43.40 11/46.34 9/43.97 14/44.69 | |POLY-3 PERCENT (g) | 27.7% 23.7% 20.5% 31.3% | |TERMINAL (d) | 11/37 (30%) 10/41 (24%) 9/39 (23%) 13/39 (33%) | |FIRST INCIDENCE | 682 708 733 (T) 723 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.365 P=0.390N P=0.264N P=0.469 | |POLY 3 | P=0.345 P=0.428N P=0.297N P=0.443 | |POLY 1.5 | P=0.348 P=0.435N P=0.296N P=0.442 | |POLY 6 | P=0.342 P=0.423N P=0.299N P=0.443 | |LOGISTIC REGRESSION| P=0.366 P=0.411N P=0.287N P=0.465 | |COCH-ARM / FISHERS | P=0.335 P=0.477N P=0.311N P=0.409 | |ORDER RESTRICTED | P=0.342 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/45 (24%) 9/48 (19%) 17/47 (36%) 17/45 (38%) | |POLY-3 RATE (b) | 11/42.84 9/47.22 17/46.42 17/44.90 | |POLY-3 PERCENT (g) | 25.7% 19.1% 36.6% 37.9% | |TERMINAL (d) | 6/37 (16%) 4/41 (10%) 12/39 (31%) 13/39 (33%) | |FIRST INCIDENCE | 639 590 193 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.063 P=0.327N P=0.182 P=0.186 | |POLY 3 | P=0.044 * P=0.310N P=0.189 P=0.161 | |POLY 1.5 | P=0.043 * P=0.310N P=0.188 P=0.156 | |POLY 6 | P=0.045 * P=0.311N P=0.184 P=0.162 | |LOGISTIC REGRESSION| P=0.024 * P=0.349N P=0.150 P=0.128 | |COCH-ARM / FISHERS | P=0.035 * P=0.339N P=0.160 P=0.127 | |ORDER RESTRICTED | P=0.086 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/45 (31%) 4/48 (8%) 8/47 (17%) 9/45 (20%) | |POLY-3 RATE (b) | 14/42.38 4/46.24 8/43.97 9/44.00 | |POLY-3 PERCENT (g) | 33.0% 8.7% 18.2% 20.5% | |TERMINAL (d) | 11/37 (30%) 4/41 (10%) 8/39 (21%) 9/39 (23%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.303N P=0.006N** P=0.094N P=0.142N | |POLY 3 | P=0.317N P=0.004N** P=0.089N P=0.140N | |POLY 1.5 | P=0.320N P=0.004N** P=0.086N P=0.142N | |POLY 6 | P=0.316N P=0.004N** P=0.096N P=0.141N | |LOGISTIC REGRESSION| P=0.295N P=0.005N** P=0.090N P=0.134N | |COCH-ARM / FISHERS | P=0.334N P=0.005N** P=0.090N P=0.167N | |ORDER RESTRICTED | P=0.029N* (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Stomach: Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/45 (0%) 0/48 (0%) 2/47 (4%) 0/46 (0%) | |POLY-3 RATE (b) | 0/42.19 0/46.24 2/43.97 0/44.43 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 2/39 (5%) 0/39 (0%) | |FIRST INCIDENCE | --- --- 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.589 (e) P=0.250 (e) | |POLY 3 | P=0.599 (e) P=0.246 (e) | |POLY 1.5 | P=0.598 (e) P=0.248 (e) | |POLY 6 | P=0.598 (e) P=0.244 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.250 (e) | |COCH-ARM / FISHERS | P=0.585 (e) P=0.258 (e) | |ORDER RESTRICTED | P=0.255 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Stomach: Forestomach, Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/45 (7%) 4/48 (8%) 8/47 (17%) 6/46 (13%) | |POLY-3 RATE (b) | 3/42.19 4/46.24 8/44.35 6/44.43 | |POLY-3 PERCENT (g) | 7.1% 8.7% 18.0% 13.5% | |TERMINAL (d) | 3/37 (8%) 4/41 (10%) 7/39 (18%) 6/39 (15%) | |FIRST INCIDENCE | 733 (T) 733 (T) 627 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.168 P=0.556 P=0.117 P=0.267 | |POLY 3 | P=0.172 P=0.550 P=0.114 P=0.268 | |POLY 1.5 | P=0.172 P=0.551 P=0.116 P=0.268 | |POLY 6 | P=0.170 P=0.548 P=0.112 P=0.266 | |LOGISTIC REGRESSION| P=0.169 P=0.556 P=0.113 P=0.267 | |COCH-ARM / FISHERS | P=0.161 P=0.536 P=0.113 P=0.254 | |ORDER RESTRICTED | P=0.169 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Stomach: Glandular | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/45 (2%) 2/48 (4%) 1/47 (2%) 0/46 (0%) | |POLY-3 RATE (b) | 1/42.19 2/46.24 1/43.97 0/44.43 | |POLY-3 PERCENT (g) | 2.4% 4.3% 2.3% 0.0% | |TERMINAL (d) | 1/37 (3%) 2/41 (5%) 1/39 (3%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.232N P=0.536 P=0.750N P=0.489N | |POLY 3 | P=0.231N P=0.532 P=0.751N P=0.490N | |POLY 1.5 | P=0.230N P=0.532 P=0.750N P=0.490N | |POLY 6 | P=0.231N P=0.531 P=0.754N P=0.490N | |LOGISTIC REGRESSION| P=0.232N P=0.536 P=0.750N (e) | |COCH-ARM / FISHERS | P=0.235N P=0.524 P=0.742N P=0.495N | |ORDER RESTRICTED | P=0.235N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/43 (5%) 2/45 (4%) 1/45 (2%) 0/43 (0%) | |POLY-3 RATE (b) | 2/40.97 2/43.52 1/42.53 0/41.32 | |POLY-3 PERCENT (g) | 4.9% 4.6% 2.4% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/39 (0%) 0/38 (0%) 0/38 (0%) | |FIRST INCIDENCE | 695 690 620 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.121N P=0.654N P=0.485N P=0.223N | |POLY 3 | P=0.123N P=0.672N P=0.487N P=0.235N | |POLY 1.5 | P=0.122N P=0.672N P=0.486N P=0.235N | |POLY 6 | P=0.123N P=0.671N P=0.487N P=0.235N | |LOGISTIC REGRESSION| P=0.125N P=0.684N P=0.483N P=0.237N | |COCH-ARM / FISHERS | P=0.122N P=0.674N P=0.483N P=0.247N | |ORDER RESTRICTED | P=0.153N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/43 (5%) 1/45 (2%) 2/45 (4%) 2/43 (5%) | |POLY-3 RATE (b) | 2/40.97 1/43.34 2/42.14 2/41.32 | |POLY-3 PERCENT (g) | 4.9% 2.3% 4.8% 4.8% | |TERMINAL (d) | 1/35 (3%) 1/39 (3%) 2/38 (5%) 2/38 (5%) | |FIRST INCIDENCE | 695 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.538 P=0.464N P=0.669N P=0.665N | |POLY 3 | P=0.514 P=0.480N P=0.684N P=0.691N | |POLY 1.5 | P=0.514 P=0.480N P=0.681N P=0.690N | |POLY 6 | P=0.515 P=0.481N P=0.686N P=0.690N | |LOGISTIC REGRESSION| P=0.516 P=0.482N P=0.683N P=0.692N | |COCH-ARM / FISHERS | P=0.513 P=0.483N P=0.674N P=0.692N | |ORDER RESTRICTED | P=0.604 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thymus | | Ectopic Parathyroid Gland | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/43 (9%) 7/45 (16%) 4/45 (9%) 7/43 (16%) | |POLY-3 RATE (b) | 4/40.82 7/43.34 4/42.14 7/41.63 | |POLY-3 PERCENT (g) | 9.8% 16.2% 9.5% 16.8% | |TERMINAL (d) | 4/35 (11%) 7/39 (18%) 4/38 (11%) 6/38 (16%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.337 P=0.324 P=0.599N P=0.307 | |POLY 3 | P=0.305 P=0.295 P=0.626N P=0.271 | |POLY 1.5 | P=0.304 P=0.296 P=0.622N P=0.270 | |POLY 6 | P=0.311 P=0.297 P=0.628N P=0.277 | |LOGISTIC REGRESSION| P=0.302 P=0.324 P=0.599N P=0.265 | |COCH-ARM / FISHERS | P=0.296 P=0.288 P=0.617N P=0.260 | |ORDER RESTRICTED | P=0.279 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/43 (5%) 3/45 (7%) 5/45 (11%) 6/43 (14%) | |POLY-3 RATE (b) | 2/41.02 3/43.34 5/42.14 6/41.32 | |POLY-3 PERCENT (g) | 4.9% 6.9% 11.9% 14.5% | |TERMINAL (d) | 0/35 (0%) 3/39 (8%) 5/38 (13%) 6/38 (16%) | |FIRST INCIDENCE | 682 733 (T) 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.088 P=0.540 P=0.244 P=0.160 | |POLY 3 | P=0.073 P=0.525 P=0.226 P=0.134 | |POLY 1.5 | P=0.074 P=0.526 P=0.230 P=0.135 | |POLY 6 | P=0.073 P=0.524 P=0.223 P=0.134 | |LOGISTIC REGRESSION| P=0.076 P=0.526 P=0.228 P=0.136 | |COCH-ARM / FISHERS | P=0.073 P=0.522 P=0.236 P=0.133 | |ORDER RESTRICTED | P=0.106 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland | | Ultimobranchial Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 2/48 (4%) 2/47 (4%) 0/47 (0%) | |POLY-3 RATE (b) | 0/42.21 2/46.24 2/43.97 0/44.65 | |POLY-3 PERCENT (g) | 0.0% 4.3% 4.6% 0.0% | |TERMINAL (d) | 0/36 (0%) 2/41 (5%) 2/39 (5%) 0/39 (0%) | |FIRST INCIDENCE | --- 733 (T) 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.473N P=0.267 P=0.256 (e) | |POLY 3 | P=0.467N P=0.258 P=0.246 (e) | |POLY 1.5 | P=0.469N P=0.256 P=0.246 (e) | |POLY 6 | P=0.465N P=0.260 P=0.246 (e) | |LOGISTIC REGRESSION| (e) P=0.267 P=0.256 (e) | |COCH-ARM / FISHERS | P=0.483N P=0.258 P=0.253 (e) | |ORDER RESTRICTED | P=0.277N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/46 (15%) 10/48 (21%) 6/47 (13%) 9/47 (19%) | |POLY-3 RATE (b) | 7/42.55 10/46.50 6/43.97 9/44.75 | |POLY-3 PERCENT (g) | 16.5% 21.5% 13.6% 20.1% | |TERMINAL (d) | 5/36 (14%) 8/41 (20%) 6/39 (15%) 7/39 (18%) | |FIRST INCIDENCE | 682 690 733 (T) 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.497 P=0.401 P=0.448N P=0.458 | |POLY 3 | P=0.481 P=0.369 P=0.475N P=0.435 | |POLY 1.5 | P=0.484 P=0.364 P=0.473N P=0.435 | |POLY 6 | P=0.478 P=0.374 P=0.479N P=0.434 | |LOGISTIC REGRESSION| P=0.485 P=0.365 P=0.468N P=0.440 | |COCH-ARM / FISHERS | P=0.467 P=0.331 P=0.483N P=0.411 | |ORDER RESTRICTED | P=0.520 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Tongue | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 3/48 (6%) 1/47 (2%) 3/47 (6%) | |POLY-3 RATE (b) | 0/43.21 3/46.72 1/43.97 3/44.65 | |POLY-3 PERCENT (g) | 0.0% 6.4% 2.3% 6.7% | |TERMINAL (d) | 0/37 (0%) 2/41 (5%) 1/39 (3%) 3/39 (8%) | |FIRST INCIDENCE | --- 590 733 (T) 733 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.179 P=0.140 P=0.511 P=0.130 | |POLY 3 | P=0.182 P=0.133 P=0.504 P=0.125 | |POLY 1.5 | P=0.182 P=0.131 P=0.503 P=0.124 | |POLY 6 | P=0.183 P=0.136 P=0.504 P=0.125 | |LOGISTIC REGRESSION| P=0.173 P=0.104 P=0.511 P=0.130 | |COCH-ARM / FISHERS | P=0.173 P=0.125 P=0.500 P=0.121 | |ORDER RESTRICTED | P=0.081 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Tongue: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 2/48 (4%) 2/47 (4%) 0/47 (0%) | |POLY-3 RATE (b) | 1/43.21 2/46.26 2/44.37 0/44.65 | |POLY-3 PERCENT (g) | 2.3% 4.3% 4.5% 0.0% | |TERMINAL (d) | 1/37 (3%) 1/41 (2%) 1/39 (3%) 0/39 (0%) | |FIRST INCIDENCE | 733 (T) 729 620 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.287N P=0.535 P=0.515 P=0.489N | |POLY 3 | P=0.282N P=0.524 P=0.509 P=0.493N | |POLY 1.5 | P=0.283N P=0.521 P=0.508 P=0.494N | |POLY 6 | P=0.281N P=0.526 P=0.511 P=0.493N | |LOGISTIC REGRESSION| P=0.292N P=0.533 P=0.497 (e) | |COCH-ARM / FISHERS | P=0.291N P=0.508 P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.234N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Inclusion Body Intracytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/46 (30%) 33/48 (69%) 44/47 (94%) 44/44 (100%) | |POLY-3 RATE (b) | 14/44.52 33/46.93 44/45.67 44/44.00 | |POLY-3 PERCENT (g) | 31.5% 70.3% 96.3% 100.0% | |TERMINAL (d) | 10/37 (27%) 32/41 (78%) 39/39 (100%) 39/39 (100%) | |FIRST INCIDENCE | 122 498 498 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 36 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Infiltration Cellular Lymphocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/46 (63%) 22/48 (46%) 24/47 (51%) 26/44 (59%) | |POLY-3 RATE (b) | 29/44.19 22/46.82 24/44.10 26/43.19 | |POLY-3 PERCENT (g) | 65.6% 47.0% 54.4% 60.2% | |TERMINAL (d) | 26/37 (70%) 20/41 (49%) 23/39 (59%) 23/39 (59%) | |FIRST INCIDENCE | 518 590 700 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.400N P=0.041N* P=0.127N P=0.239N | |POLY 3 | P=0.531 P=0.054N P=0.193N P=0.380N | |POLY 1.5 | P=0.529 P=0.056N P=0.180N P=0.386N | |POLY 6 | P=0.535 P=0.052N P=0.206N P=0.371N | |LOGISTIC REGRESSION| P=0.499N P=0.056N P=0.168N P=0.346N | |COCH-ARM / FISHERS | P=0.506 P=0.071N P=0.169N P=0.433N | |ORDER RESTRICTED | P=0.204N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Uterus | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 4/48 (8%) 3/47 (6%) 1/46 (2%) | |POLY-3 RATE (b) | 0/43.18 4/46.72 3/43.97 1/44.74 | |POLY-3 PERCENT (g) | 0.0% 8.6% 6.8% 2.2% | |TERMINAL (d) | 0/37 (0%) 3/41 (7%) 3/39 (8%) 0/39 (0%) | |FIRST INCIDENCE | --- 590 733 (T) 647 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.570N P=0.078 P=0.130 P=0.505 | |POLY 3 | P=0.561N P=0.071 P=0.122 P=0.507 | |POLY 1.5 | P=0.566N P=0.070 P=0.122 P=0.506 | |POLY 6 | P=0.554N P=0.072 P=0.121 P=0.509 | |LOGISTIC REGRESSION| P=0.592N P=0.059 P=0.130 P=0.454 | |COCH-ARM / FISHERS | P=0.581N P=0.064 P=0.125 P=0.500 | |ORDER RESTRICTED | P=0.142 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 37 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 42/46 (91%) 46/48 (96%) 47/47 (100%) 43/46 (93%) | |POLY-3 RATE (b) | 42/44.88 46/47.52 47/47.00 43/45.45 | |POLY-3 PERCENT (g) | 93.6% 96.8% 100.0% 94.6% | |TERMINAL (d) | 35/37 (95%) 40/41 (98%) 39/39 (100%) 38/39 (97%) | |FIRST INCIDENCE | 518 498 193 553 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.465N P=0.562N P=0.320 P=0.482N | |POLY 3 | P=0.542 P=0.404 P=0.116 P=0.597 | |POLY 1.5 | P=0.556 P=0.420 P=0.106 P=0.611 | |POLY 6 | P=0.510 P=0.376 P=0.123 P=0.569 | |LOGISTIC REGRESSION| P=0.536 P=0.456 P=0.055 P=0.661 | |COCH-ARM / FISHERS | P=0.440 P=0.318 P=0.056 P=0.500 | |ORDER RESTRICTED | P=0.258 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Uterus | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 1/48 (2%) 3/47 (6%) 0/46 (0%) | |POLY-3 RATE (b) | 0/43.18 1/46.72 3/43.97 0/44.43 | |POLY-3 PERCENT (g) | 0.0% 2.1% 6.8% 0.0% | |TERMINAL (d) | 0/37 (0%) 0/41 (0%) 3/39 (8%) 0/39 (0%) | |FIRST INCIDENCE | --- 590 733 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.630N P=0.513 P=0.130 (e) | |POLY 3 | P=0.627N P=0.516 P=0.122 (e) | |POLY 1.5 | P=0.629N P=0.514 P=0.122 (e) | |POLY 6 | P=0.625N P=0.518 P=0.121 (e) | |LOGISTIC REGRESSION| P=0.619 P=0.423 P=0.130 (e) | |COCH-ARM / FISHERS | P=0.629 P=0.511 P=0.125 (e) | |ORDER RESTRICTED | P=0.224 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93029 TEST: 04 Page 38 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 91 PPM 204 PPM 408 PPM | | | | |=================================================================================================================================| | | |Vagina: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/45 (2%) 0/47 (0%) 0/47 (0%) 3/46 (7%) | |POLY-3 RATE (b) | 1/42.31 0/45.41 0/43.97 3/44.49 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 6.7% | |TERMINAL (d) | 1/37 (3%) 0/41 (0%) 0/39 (0%) 2/39 (5%) | |FIRST INCIDENCE | 733 (T) --- --- 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087 P=0.480N P=0.489N P=0.332 | |POLY 3 | P=0.081 P=0.486N P=0.492N P=0.323 | |POLY 1.5 | P=0.081 P=0.487N P=0.492N P=0.322 | |POLY 6 | P=0.080 P=0.485N P=0.493N P=0.326 | |LOGISTIC REGRESSION| P=0.085 (e) (e) P=0.324 | |COCH-ARM / FISHERS | P=0.082 P=0.489N P=0.489N P=0.317 | |ORDER RESTRICTED | P=0.043 * (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).