TDMS Study 93005-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR MALACHITE GREEN DATE: 06/19/03 EXPERIMENT: 93005 TEST: 04 TIME: 07:25:41 TEST TYPE: CHRONIC PAGE: 1 CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93005 PATHOLOGIST: TROTTER, RONALD CAS: 569-64-2 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR MALACHITE GREEN DATE: 06/19/03 EXPERIMENT: 93005 TEST: 04 TIME: 07:25:41 TEST TYPE: CHRONIC CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93005 PATHOLOGIST: TROTTER, RONALD CAS: 569-64-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF MALACHITE GREEN =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Hypertrophy Focal Bone: Sternum Fibrous Osteodystrophy Clitoral Gland: Duct Cyst Kidney: Glomerulus Amyloid Deposition Kidney: Pelvis Dilatation Kidney: Renal Tubule Accumulation, Hyaline Droplet Liver Infiltration Cellular Lymphocyte Necrosis Lung Proteinosis Ovary Atrophy Pancreas: Acinus Atrophy Salivary Glands: Submandibular Gland Infiltration Cellular Lymphocyte Stomach, Forestomach: Epithelium Hyperplasia Focal Tongue: Artery Inflammation Chronic Urinary Bladder Inclusion Body Intracytoplasmic Infiltration Cellular Lymphocyte =============================================================== Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/47 (0%) 1/45 (2%) 3/47 (6%) | |POLY-3 RATE (b) | 0/44.14 0/46.38 1/42.40 3/44.42 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 6.8% | |TERMINAL (d) | 0/39 (0%) 0/44 (0%) 1/40 (3%) 2/40 (5%) | |FIRST INCIDENCE | --- --- 727 (T) 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.019 * (e) P=0.505 P=0.126 | |POLY 3 | P=0.018 * (e) P=0.492 P=0.120 | |POLY 1.5 | P=0.018 * (e) P=0.491 P=0.118 | |POLY 6 | P=0.019 * (e) P=0.495 P=0.123 | |LOGISTIC REGRESSION| P=0.020 * (e) P=0.505 P=0.121 | |COCH-ARM / FISHERS | P=0.020 * (e) P=0.489 P=0.121 | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 46/47 (98%) 46/47 (98%) 44/45 (98%) 45/47 (96%) | |POLY-3 RATE (b) | 46/46.14 46/47.00 44/45.00 45/45.67 | |POLY-3 PERCENT (g) | 99.7% 97.9% 97.8% 98.5% | |TERMINAL (d) | 39/39 (100%) 43/44 (98%) 39/40 (98%) 40/40 (100%) | |FIRST INCIDENCE | 562 644 226 318 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.494N P=0.104N P=0.306N P=0.379N | |POLY 3 | P=0.538N P=0.559N P=0.550N P=0.753N | |POLY 1.5 | P=0.511N P=0.640N P=0.630N P=0.691N | |POLY 6 | P=0.597N P=0.512N P=0.503N P=0.907N | |LOGISTIC REGRESSION| P=0.601N P=0.459N P=0.710 P=0.791 | |COCH-ARM / FISHERS | P=0.348N P=0.753N P=0.742N P=0.500N | |ORDER RESTRICTED | P=0.396N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Bone: Femur | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 5/48 (10%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 4/45.14 5/46.93 2/43.58 2/45.08 | |POLY-3 PERCENT (g) | 8.9% 10.7% 4.6% 4.4% | |TERMINAL (d) | 4/40 (10%) 5/44 (11%) 2/40 (5%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.560 P=0.337N P=0.325N | |POLY 3 | P=0.178N P=0.524 P=0.353N P=0.338N | |POLY 1.5 | P=0.179N P=0.515 P=0.352N P=0.342N | |POLY 6 | P=0.174N P=0.535 P=0.349N P=0.331N | |LOGISTIC REGRESSION| P=0.173N P=0.560 P=0.337N P=0.325N | |COCH-ARM / FISHERS | P=0.171N P=0.500 P=0.339N P=0.339N | |ORDER RESTRICTED | P=0.261N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Bone: Sternum | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 4/48 (8%) 3/48 (6%) | |POLY-3 RATE (b) | 0/45.14 2/46.93 4/43.58 3/45.08 | |POLY-3 PERCENT (g) | 0.0% 4.3% 9.2% 6.7% | |TERMINAL (d) | 0/40 (0%) 2/44 (5%) 4/40 (10%) 3/41 (7%) | |FIRST INCIDENCE | --- 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.110 P=0.260 P=0.063 P=0.126 | |POLY 3 | P=0.110 P=0.246 P=0.056 P=0.118 | |POLY 1.5 | P=0.109 P=0.243 P=0.056 P=0.117 | |POLY 6 | P=0.113 P=0.250 P=0.057 P=0.121 | |LOGISTIC REGRESSION| (e) P=0.260 P=0.063 P=0.126 | |COCH-ARM / FISHERS | P=0.114 P=0.247 P=0.059 P=0.121 | |ORDER RESTRICTED | P=0.062 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Bone: Sternum | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/48 (25%) 14/48 (29%) 5/48 (10%) 5/48 (10%) | |POLY-3 RATE (b) | 12/45.14 14/46.93 5/43.58 5/45.08 | |POLY-3 PERCENT (g) | 26.6% 29.8% 11.5% 11.1% | |TERMINAL (d) | 12/40 (30%) 14/44 (32%) 5/40 (13%) 5/41 (12%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010N* P=0.522 P=0.052N P=0.046N* | |POLY 3 | P=0.011N* P=0.455 P=0.060N P=0.051N | |POLY 1.5 | P=0.011N* P=0.438 P=0.060N P=0.054N | |POLY 6 | P=0.010N* P=0.474 P=0.057N P=0.048N* | |LOGISTIC REGRESSION| P=0.010N* P=0.522 P=0.052N P=0.046N* | |COCH-ARM / FISHERS | P=0.011N* P=0.409 P=0.053N P=0.053N | |ORDER RESTRICTED | P=0.026N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Brain: Cerebrum | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 25/48 (52%) 18/48 (38%) 17/48 (35%) 17/48 (35%) | |POLY-3 RATE (b) | 25/46.85 18/46.99 17/44.52 17/45.38 | |POLY-3 PERCENT (g) | 53.4% 38.3% 38.2% 37.5% | |TERMINAL (d) | 19/40 (48%) 17/44 (39%) 13/40 (33%) 15/41 (37%) | |FIRST INCIDENCE | 562 711 568 673 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.111N P=0.067N P=0.101N P=0.079N | |POLY 3 | P=0.115N P=0.103N P=0.106N P=0.091N | |POLY 1.5 | P=0.111N P=0.103N P=0.098N P=0.088N | |POLY 6 | P=0.116N P=0.108N P=0.107N P=0.095N | |LOGISTIC REGRESSION| P=0.102N P=0.102N P=0.088N P=0.078N | |COCH-ARM / FISHERS | P=0.090N P=0.109N P=0.075N P=0.075N | |ORDER RESTRICTED | P=0.091N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 44/48 (92%) 47/47 (100%) 45/46 (98%) 44/44 (100%) | |POLY-3 RATE (b) | 44/46.93 47/47.00 45/45.03 44/44.00 | |POLY-3 PERCENT (g) | 93.8% 100.0% 99.9% 100.0% | |TERMINAL (d) | 38/40 (95%) 43/43 (100%) 40/40 (100%) 39/39 (100%) | |FIRST INCIDENCE | 562 596 442 626 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406 P=0.594N P=0.482 P=0.511 | |POLY 3 | P=0.051 P=0.112 P=0.124 P=0.124 | |POLY 1.5 | P=0.039 * P=0.088 P=0.116 P=0.099 | |POLY 6 | P=0.066 P=0.138 P=0.146 P=0.150 | |LOGISTIC REGRESSION| P=0.034 * P=0.131 P=0.068 P=0.148 | |COCH-ARM / FISHERS | P=0.050 P=0.061 P=0.194 P=0.070 | |ORDER RESTRICTED | P=0.007 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Eye: Bilateral, Lens | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 2/48 (4%) 5/47 (11%) 2/48 (4%) | |POLY-3 RATE (b) | 4/46.17 2/47.38 5/45.05 2/45.08 | |POLY-3 PERCENT (g) | 8.7% 4.2% 11.1% 4.4% | |TERMINAL (d) | 1/40 (3%) 1/44 (2%) 1/40 (3%) 2/41 (5%) | |FIRST INCIDENCE | 562 596 444 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.390N P=0.317N P=0.488 P=0.338N | |POLY 3 | P=0.402N P=0.326N P=0.485 P=0.348N | |POLY 1.5 | P=0.399N P=0.330N P=0.482 P=0.347N | |POLY 6 | P=0.404N P=0.322N P=0.491 P=0.349N | |LOGISTIC REGRESSION| P=0.292N P=0.514N P=0.574 P=0.315N | |COCH-ARM / FISHERS | P=0.380N P=0.339N P=0.486 P=0.339N | |ORDER RESTRICTED | P=0.345N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Eye: Lens | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 4/48 (8%) 6/47 (13%) 8/48 (17%) | |POLY-3 RATE (b) | 5/46.17 4/47.38 6/45.05 8/46.27 | |POLY-3 PERCENT (g) | 10.8% 8.4% 13.3% 17.3% | |TERMINAL (d) | 2/40 (5%) 3/44 (7%) 2/40 (5%) 6/41 (15%) | |FIRST INCIDENCE | 562 596 444 161 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.154 P=0.459N P=0.489 P=0.292 | |POLY 3 | P=0.146 P=0.484N P=0.483 P=0.277 | |POLY 1.5 | P=0.147 P=0.489N P=0.480 P=0.276 | |POLY 6 | P=0.147 P=0.479N P=0.489 P=0.279 | |LOGISTIC REGRESSION| P=0.211 P=0.640N P=0.555 P=0.319 | |COCH-ARM / FISHERS | P=0.150 P=0.500N P=0.485 P=0.276 | |ORDER RESTRICTED | P=0.209 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 5/48 (10%) 5/48 (10%) 4/48 (8%) | |POLY-3 RATE (b) | 4/45.14 5/46.93 5/43.58 4/45.08 | |POLY-3 PERCENT (g) | 8.9% 10.7% 11.5% 8.9% | |TERMINAL (d) | 4/40 (10%) 5/44 (11%) 5/40 (13%) 4/41 (10%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.537N P=0.560 P=0.500 P=0.631N | |POLY 3 | P=0.542N P=0.524 P=0.478 P=0.642 | |POLY 1.5 | P=0.544N P=0.515 P=0.480 P=0.638 | |POLY 6 | P=0.535N P=0.535 P=0.483 P=0.636N | |LOGISTIC REGRESSION| P=0.537N P=0.560 P=0.500 P=0.631N | |COCH-ARM / FISHERS | P=0.529N P=0.500 P=0.500 P=0.643N | |ORDER RESTRICTED | P=0.635 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Heart | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/45.14 0/46.93 2/43.79 0/45.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/40 (0%) 0/44 (0%) 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | --- --- 694 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.586 (e) P=0.245 (e) | |POLY 3 | P=0.580 (e) P=0.230 (e) | |POLY 1.5 | P=0.577 (e) P=0.231 (e) | |POLY 6 | P=0.584 (e) P=0.233 (e) | |LOGISTIC REGRESSION| P=0.586 (e) P=0.235 (e) | |COCH-ARM / FISHERS | P=0.584 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.241 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 7/47 (15%) 3/48 (6%) 2/47 (4%) | |POLY-3 RATE (b) | 2/45.14 7/46.38 3/43.66 2/45.07 | |POLY-3 PERCENT (g) | 4.4% 15.1% 6.9% 4.4% | |TERMINAL (d) | 2/40 (5%) 7/44 (16%) 2/40 (5%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) 707 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300N P=0.105 P=0.502 P=0.686N | |POLY 3 | P=0.294N P=0.085 P=0.485 P=0.693 | |POLY 1.5 | P=0.299N P=0.081 P=0.486 P=0.690 | |POLY 6 | P=0.286N P=0.091 P=0.489 P=0.689N | |LOGISTIC REGRESSION| P=0.294N P=0.105 P=0.490 P=0.686N | |COCH-ARM / FISHERS | P=0.302N P=0.074 P=0.500 P=0.684 | |ORDER RESTRICTED | P=0.267N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Kidney: Glomerulus | | Amyloid Deposition | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 2/47 (4%) | |POLY-3 RATE (b) | 0/45.14 0/46.38 0/43.58 2/45.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.4% | |TERMINAL (d) | 0/40 (0%) 0/44 (0%) 0/40 (0%) 1/41 (2%) | |FIRST INCIDENCE | --- --- --- 723 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.046 * (e) (e) P=0.248 | |POLY 3 | P=0.043 * (e) (e) P=0.237 | |POLY 1.5 | P=0.043 * (e) (e) P=0.235 | |POLY 6 | P=0.043 * (e) (e) P=0.240 | |LOGISTIC REGRESSION| P=0.045 * (e) (e) P=0.244 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) P=0.242 | |ORDER RESTRICTED | P=0.029 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 0/48 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/45.43 0/46.38 0/43.58 0/45.07 | |POLY-3 PERCENT (g) | 4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/40 (3%) 0/44 (0%) 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 647 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.126N P=0.227N P=0.245N P=0.239N | |POLY 3 | P=0.128N P=0.233N P=0.247N P=0.239N | |POLY 1.5 | P=0.126N P=0.236N P=0.245N P=0.241N | |POLY 6 | P=0.130N P=0.229N P=0.246N P=0.237N | |LOGISTIC REGRESSION| P=0.119N P=0.278N P=0.229N P=0.244N | |COCH-ARM / FISHERS | P=0.123N P=0.253N P=0.247N P=0.253N | |ORDER RESTRICTED | P=0.030N* (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 0/47 (0%) 1/48 (2%) 1/47 (2%) | |POLY-3 RATE (b) | 4/46.30 0/46.38 1/43.79 1/45.07 | |POLY-3 PERCENT (g) | 8.6% 0.0% 2.3% 2.2% | |TERMINAL (d) | 0/40 (0%) 0/44 (0%) 0/40 (0%) 1/41 (2%) | |FIRST INCIDENCE | 562 --- 673 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.185N P=0.061N P=0.194N P=0.184N | |POLY 3 | P=0.187N P=0.060N P=0.196N P=0.187N | |POLY 1.5 | P=0.185N P=0.061N P=0.192N P=0.187N | |POLY 6 | P=0.188N P=0.059N P=0.198N P=0.188N | |LOGISTIC REGRESSION| P=0.161N P=0.125N P=0.133N P=0.183N | |COCH-ARM / FISHERS | P=0.180N P=0.061N P=0.181N P=0.187N | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 1/48 (2%) 3/46 (7%) 0/48 (0%) | |POLY-3 RATE (b) | 1/45.14 1/46.93 3/43.32 0/45.08 | |POLY-3 PERCENT (g) | 2.2% 2.1% 6.9% 0.0% | |TERMINAL (d) | 1/40 (3%) 1/44 (2%) 3/40 (8%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.417N P=0.740N P=0.305 P=0.495N | |POLY 3 | P=0.422N P=0.752N P=0.291 P=0.500N | |POLY 1.5 | P=0.424N P=0.755N P=0.289 P=0.502N | |POLY 6 | P=0.418N P=0.748N P=0.295 P=0.498N | |LOGISTIC REGRESSION| P=0.417N P=0.740N P=0.305 (e) | |COCH-ARM / FISHERS | P=0.415N P=0.753N P=0.292 P=0.500N | |ORDER RESTRICTED | P=0.224N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 1/48 (2%) 0/46 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 2/45.43 1/46.93 0/43.32 2/45.08 | |POLY-3 PERCENT (g) | 4.4% 2.1% 0.0% 4.4% | |TERMINAL (d) | 1/40 (3%) 1/44 (2%) 0/40 (0%) 2/41 (5%) | |FIRST INCIDENCE | 647 727 (T) --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.581 P=0.475N P=0.245N P=0.689N | |POLY 3 | P=0.577 P=0.489N P=0.248N P=0.691 | |POLY 1.5 | P=0.578 P=0.493N P=0.249N P=0.689 | |POLY 6 | P=0.578 P=0.485N P=0.246N P=0.693N | |LOGISTIC REGRESSION| P=0.583 P=0.531N P=0.240N P=0.694 | |COCH-ARM / FISHERS | P=0.585 P=0.500N P=0.258N P=0.692N | |ORDER RESTRICTED | P=0.411 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 6/48 (13%) 8/46 (17%) 12/48 (25%) | |POLY-3 RATE (b) | 4/45.14 6/46.93 8/43.40 12/45.73 | |POLY-3 PERCENT (g) | 8.9% 12.8% 18.4% 26.2% | |TERMINAL (d) | 4/40 (10%) 6/44 (14%) 7/40 (18%) 8/41 (20%) | |FIRST INCIDENCE | 727 (T) 727 (T) 707 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.014 * P=0.430 P=0.179 P=0.036 * | |POLY 3 | P=0.012 * P=0.394 P=0.157 P=0.027 * | |POLY 1.5 | P=0.012 * P=0.385 P=0.155 P=0.025 * | |POLY 6 | P=0.014 * P=0.405 P=0.164 P=0.030 * | |LOGISTIC REGRESSION| P=0.012 * P=0.430 P=0.172 P=0.027 * | |COCH-ARM / FISHERS | P=0.013 * P=0.370 P=0.157 P=0.026 * | |ORDER RESTRICTED | P=0.016 * (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 9/48 (19%) 8/46 (17%) 4/48 (8%) | |POLY-3 RATE (b) | 5/45.14 9/46.93 8/43.32 4/45.08 | |POLY-3 PERCENT (g) | 11.1% 19.2% 18.5% 8.9% | |TERMINAL (d) | 5/40 (13%) 9/44 (21%) 8/40 (20%) 4/41 (10%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.302N P=0.248 P=0.273 P=0.484N | |POLY 3 | P=0.309N P=0.215 P=0.249 P=0.501N | |POLY 1.5 | P=0.314N P=0.207 P=0.245 P=0.506N | |POLY 6 | P=0.300N P=0.224 P=0.256 P=0.492N | |LOGISTIC REGRESSION| P=0.302N P=0.248 P=0.273 P=0.484N | |COCH-ARM / FISHERS | P=0.301N P=0.193 P=0.249 P=0.500N | |ORDER RESTRICTED | P=0.253N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/46 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 0/45.14 0/46.93 0/43.32 2/45.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.4% | |TERMINAL (d) | 0/40 (0%) 0/44 (0%) 0/40 (0%) 2/41 (5%) | |FIRST INCIDENCE | --- --- --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.044 * (e) (e) P=0.244 | |POLY 3 | P=0.044 * (e) (e) P=0.237 | |POLY 1.5 | P=0.044 * (e) (e) P=0.235 | |POLY 6 | P=0.044 * (e) (e) P=0.240 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.244 | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.029 * (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/48 (21%) 7/48 (15%) 8/46 (17%) 6/48 (13%) | |POLY-3 RATE (b) | 10/45.14 7/46.93 8/43.84 6/45.09 | |POLY-3 PERCENT (g) | 22.2% 14.9% 18.3% 13.3% | |TERMINAL (d) | 10/40 (25%) 7/44 (16%) 7/40 (18%) 5/41 (12%) | |FIRST INCIDENCE | 727 (T) 727 (T) 568 723 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.216N P=0.224N P=0.399N P=0.190N | |POLY 3 | P=0.225N P=0.266N P=0.423N P=0.205N | |POLY 1.5 | P=0.227N P=0.278N P=0.434N P=0.211N | |POLY 6 | P=0.219N P=0.254N P=0.405N P=0.196N | |LOGISTIC REGRESSION| P=0.219N P=0.224N P=0.435N P=0.175N | |COCH-ARM / FISHERS | P=0.213N P=0.297N P=0.436N P=0.206N | |ORDER RESTRICTED | P=0.210N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 2/45.14 3/46.93 2/43.58 0/45.08 | |POLY-3 PERCENT (g) | 4.4% 6.4% 4.6% 0.0% | |TERMINAL (d) | 2/40 (5%) 3/44 (7%) 2/40 (5%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.130N P=0.544 P=0.695 P=0.233N | |POLY 3 | P=0.132N P=0.518 P=0.681 P=0.237N | |POLY 1.5 | P=0.134N P=0.511 P=0.682 P=0.239N | |POLY 6 | P=0.130N P=0.525 P=0.684 P=0.234N | |LOGISTIC REGRESSION| P=0.130N P=0.544 P=0.695 (e) | |COCH-ARM / FISHERS | P=0.129N P=0.500 P=0.692N P=0.247N | |ORDER RESTRICTED | P=0.142N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/48 (13%) 6/48 (13%) 6/48 (13%) 2/48 (4%) | |POLY-3 RATE (b) | 6/45.27 6/46.93 6/44.36 2/45.08 | |POLY-3 PERCENT (g) | 13.3% 12.8% 13.5% 4.4% | |TERMINAL (d) | 5/40 (13%) 6/44 (14%) 5/40 (13%) 2/41 (5%) | |FIRST INCIDENCE | 694 727 (T) 442 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.104N P=0.552N P=0.619N P=0.128N | |POLY 3 | P=0.106N P=0.595N P=0.606 P=0.134N | |POLY 1.5 | P=0.107N P=0.604N P=0.605 P=0.136N | |POLY 6 | P=0.103N P=0.585N P=0.614 P=0.130N | |LOGISTIC REGRESSION| P=0.103N P=0.573N P=0.619 P=0.128N | |COCH-ARM / FISHERS | P=0.100N P=0.621N P=0.621N P=0.134N | |ORDER RESTRICTED | P=0.142N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lung | | Proteinosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/48 (6%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 3/45.14 0/46.93 0/43.58 0/45.08 | |POLY-3 PERCENT (g) | 6.7% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/40 (8%) 0/44 (0%) 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.053N P=0.105N P=0.121N P=0.117N | |POLY 3 | P=0.053N P=0.112N P=0.125N P=0.119N | |POLY 1.5 | P=0.052N P=0.114N P=0.125N P=0.120N | |POLY 6 | P=0.054N P=0.109N P=0.123N P=0.116N | |LOGISTIC REGRESSION| P=0.053N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.052N P=0.121N P=0.121N P=0.121N | |ORDER RESTRICTED | P=0.008N** (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 3/48 (6%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 1/45.14 3/46.93 0/43.58 1/45.08 | |POLY-3 PERCENT (g) | 2.2% 6.4% 0.0% 2.2% | |TERMINAL (d) | 1/40 (3%) 3/44 (7%) 0/40 (0%) 1/41 (2%) | |FIRST INCIDENCE | 727 (T) 727 (T) --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.391N P=0.340 P=0.500N P=0.756N | |POLY 3 | P=0.390N P=0.320 P=0.507N P=0.760 | |POLY 1.5 | P=0.391N P=0.314 P=0.506N P=0.758 | |POLY 6 | P=0.385N P=0.326 P=0.505N P=0.758N | |LOGISTIC REGRESSION| P=0.391N P=0.340 (e) P=0.756N | |COCH-ARM / FISHERS | P=0.387N P=0.308 P=0.500N P=0.753N | |ORDER RESTRICTED | P=0.280N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 1/48 (2%) 2/47 (4%) 1/48 (2%) | |POLY-3 RATE (b) | 2/45.14 1/46.93 2/42.71 1/45.08 | |POLY-3 PERCENT (g) | 4.4% 2.1% 4.7% 2.2% | |TERMINAL (d) | 2/40 (5%) 1/44 (2%) 2/40 (5%) 1/41 (2%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.455N P=0.467N P=0.695 P=0.491N | |POLY 3 | P=0.462N P=0.486N P=0.674 P=0.500N | |POLY 1.5 | P=0.462N P=0.491N P=0.675 P=0.503N | |POLY 6 | P=0.460N P=0.481N P=0.678 P=0.496N | |LOGISTIC REGRESSION| P=0.455N P=0.467N P=0.695 P=0.491N | |COCH-ARM / FISHERS | P=0.452N P=0.500N P=0.684 P=0.500N | |ORDER RESTRICTED | P=0.444N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/45 (18%) 8/46 (17%) 5/44 (11%) 5/46 (11%) | |POLY-3 RATE (b) | 8/43.54 8/45.23 5/41.45 5/44.16 | |POLY-3 PERCENT (g) | 18.4% 17.7% 12.1% 11.3% | |TERMINAL (d) | 8/39 (21%) 7/42 (17%) 5/39 (13%) 4/40 (10%) | |FIRST INCIDENCE | 727 (T) 644 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174N P=0.546N P=0.273N P=0.258N | |POLY 3 | P=0.177N P=0.575N P=0.307N P=0.266N | |POLY 1.5 | P=0.176N P=0.582N P=0.306N P=0.267N | |POLY 6 | P=0.174N P=0.564N P=0.302N P=0.260N | |LOGISTIC REGRESSION| P=0.174N P=0.581N P=0.273N P=0.252N | |COCH-ARM / FISHERS | P=0.167N P=0.589N P=0.290N P=0.261N | |ORDER RESTRICTED | P=0.282N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/13 (31%) 4/13 (31%) 2/6 (33%) 1/9 (11%) | |POLY-3 RATE (b) | 4/12.47 4/12.23 2/5.58 1/6.87 | |POLY-3 PERCENT (g) | 32.1% 32.7% 35.8% 14.6% | |TERMINAL (d) | 4/10 (40%) 4/10 (40%) 2/3 (67%) 1/5 (20%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.379N P=0.672 P=0.442 P=0.426N | |POLY 3 | P=0.314N P=0.650 P=0.643 P=0.389N | |POLY 1.5 | P=0.298N P=0.653 P=0.649 P=0.372N | |POLY 6 | P=0.316N P=0.648 P=0.631 P=0.389N | |LOGISTIC REGRESSION| P=0.379N P=0.672 P=0.442 P=0.426N | |COCH-ARM / FISHERS | P=0.210N P=0.664N P=0.652 P=0.293N | |ORDER RESTRICTED | P=0.346N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/13 (0%) 2/13 (15%) 0/6 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 0/12.47 2/12.23 0/5.58 0/6.87 | |POLY-3 PERCENT (g) | 0.0% 16.4% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 2/10 (20%) 0/3 (0%) 0/5 (0%) | |FIRST INCIDENCE | --- 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.558N P=0.234 (e) (e) | |POLY 3 | P=0.515N P=0.225 (e) (e) | |POLY 1.5 | P=0.507N P=0.227 (e) (e) | |POLY 6 | P=0.521N P=0.223 (e) (e) | |LOGISTIC REGRESSION| (e) P=0.234 (e) (e) | |COCH-ARM / FISHERS | P=0.475N P=0.240 (e) (e) | |ORDER RESTRICTED | P=0.374 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/13 (15%) 1/13 (8%) 2/6 (33%) 1/9 (11%) | |POLY-3 RATE (b) | 2/12.47 1/12.23 2/5.58 1/6.87 | |POLY-3 PERCENT (g) | 16.0% 8.2% 35.8% 14.6% | |TERMINAL (d) | 2/10 (20%) 1/10 (10%) 2/3 (67%) 1/5 (20%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.448 P=0.500N P=0.215 P=0.746 | |POLY 3 | P=0.474 P=0.507N P=0.377 P=0.701N | |POLY 1.5 | P=0.492 P=0.504N P=0.384 P=0.690N | |POLY 6 | P=0.474 P=0.509N P=0.365 P=0.703N | |LOGISTIC REGRESSION| P=0.448 P=0.500N P=0.215 P=0.746 | |COCH-ARM / FISHERS | P=0.596 P=0.500N P=0.373 P=0.642N | |ORDER RESTRICTED | P=0.419 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/2 (100%) 3/5 (60%) 1/1 (100%) 0/0 (0%) | |POLY-3 RATE (b) | 2/2.00 3/5.00 1/1.00 0/0.00 | |POLY-3 PERCENT (g) | 100.0% 60.0% 100.0% 0.0% | |TERMINAL (d) | 2/2 (100%) 3/5 (60%) 1/1 (100%) 0/0 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.861N P=0.451N (e) (e) | |POLY 3 | (e) P=0.451N (e) (e) | |POLY 1.5 | (e) P=0.451N (e) (e) | |POLY 6 | (e) P=0.451N (e) (e) | |LOGISTIC REGRESSION| P=0.861N P=0.451N (e) (e) | |COCH-ARM / FISHERS | P=0.877N P=0.476N (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 28/48 (58%) 33/46 (72%) 36/46 (78%) 36/45 (80%) | |POLY-3 RATE (b) | 28/45.53 33/45.38 36/43.73 36/43.42 | |POLY-3 PERCENT (g) | 61.5% 72.7% 82.3% 82.9% | |TERMINAL (d) | 26/40 (65%) 33/43 (77%) 33/40 (83%) 34/39 (87%) | |FIRST INCIDENCE | 676 727 (T) 673 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * P=0.339 P=0.061 P=0.036 * | |POLY 3 | P=0.012 * P=0.176 P=0.021 * P=0.018 * | |POLY 1.5 | P=0.012 * P=0.157 P=0.021 * P=0.017 * | |POLY 6 | P=0.012 * P=0.198 P=0.025 * P=0.020 * | |LOGISTIC REGRESSION| P=0.014 * P=0.286 P=0.031 * P=0.028 * | |COCH-ARM / FISHERS | P=0.017 * P=0.126 P=0.032 * P=0.021 * | |ORDER RESTRICTED | P=0.011 * (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/48 (40%) 21/46 (46%) 14/46 (30%) 13/45 (29%) | |POLY-3 RATE (b) | 19/45.91 21/45.70 14/43.32 13/43.50 | |POLY-3 PERCENT (g) | 41.4% 46.0% 32.3% 29.9% | |TERMINAL (d) | 16/40 (40%) 19/43 (44%) 14/40 (35%) 11/39 (28%) | |FIRST INCIDENCE | 599 659 727 (T) 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.080N P=0.534 P=0.199N P=0.163N | |POLY 3 | P=0.080N P=0.410 P=0.252N P=0.180N | |POLY 1.5 | P=0.082N P=0.388 P=0.252N P=0.187N | |POLY 6 | P=0.077N P=0.434 P=0.250N P=0.171N | |LOGISTIC REGRESSION| P=0.079N P=0.401 P=0.229N P=0.183N | |COCH-ARM / FISHERS | P=0.081N P=0.350 P=0.238N P=0.193N | |ORDER RESTRICTED | P=0.137N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/48 (6%) 0/46 (0%) 1/46 (2%) 1/45 (2%) | |POLY-3 RATE (b) | 3/45.14 0/45.38 1/43.32 1/43.07 | |POLY-3 PERCENT (g) | 6.7% 0.0% 2.3% 2.3% | |TERMINAL (d) | 3/40 (8%) 0/43 (0%) 1/40 (3%) 1/39 (3%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.327N P=0.109N P=0.305N P=0.314N | |POLY 3 | P=0.338N P=0.118N P=0.320N P=0.322N | |POLY 1.5 | P=0.335N P=0.121N P=0.322N P=0.326N | |POLY 6 | P=0.340N P=0.114N P=0.315N P=0.317N | |LOGISTIC REGRESSION| P=0.327N (e) P=0.305N P=0.314N | |COCH-ARM / FISHERS | P=0.329N P=0.129N P=0.325N P=0.333N | |ORDER RESTRICTED | P=0.111N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Ovary: Bilateral | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 3/46 (7%) 3/46 (7%) 2/45 (4%) | |POLY-3 RATE (b) | 4/45.91 3/45.38 3/43.32 2/43.07 | |POLY-3 PERCENT (g) | 8.7% 6.6% 6.9% 4.6% | |TERMINAL (d) | 1/40 (3%) 3/43 (7%) 3/40 (8%) 2/39 (5%) | |FIRST INCIDENCE | 599 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.294N P=0.466N P=0.505N P=0.343N | |POLY 3 | P=0.307N P=0.506N P=0.532N P=0.367N | |POLY 1.5 | P=0.306N P=0.512N P=0.531N P=0.368N | |POLY 6 | P=0.308N P=0.501N P=0.531N P=0.366N | |LOGISTIC REGRESSION| P=0.298N P=0.602N P=0.518N P=0.370N | |COCH-ARM / FISHERS | P=0.299N P=0.524N P=0.524N P=0.370N | |ORDER RESTRICTED | P=0.356N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Ovary: Germinal Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/46 (0%) 2/46 (4%) 0/45 (0%) | |POLY-3 RATE (b) | 0/45.14 0/45.38 2/43.32 0/43.07 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/40 (0%) 0/43 (0%) 2/40 (5%) 0/39 (0%) | |FIRST INCIDENCE | --- --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.573 (e) P=0.238 (e) | |POLY 3 | P=0.576 (e) P=0.228 (e) | |POLY 1.5 | P=0.574 (e) P=0.227 (e) | |POLY 6 | P=0.579 (e) P=0.231 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.238 (e) | |COCH-ARM / FISHERS | P=0.572 (e) P=0.237 (e) | |ORDER RESTRICTED | P=0.239 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/47 (13%) 4/47 (9%) 2/44 (5%) 3/47 (6%) | |POLY-3 RATE (b) | 6/45.00 4/46.38 2/41.53 3/45.07 | |POLY-3 PERCENT (g) | 13.3% 8.6% 4.8% 6.7% | |TERMINAL (d) | 6/40 (15%) 4/44 (9%) 2/40 (5%) 3/41 (7%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.310N P=0.133N P=0.229N | |POLY 3 | P=0.182N P=0.351N P=0.160N P=0.241N | |POLY 1.5 | P=0.181N P=0.359N P=0.161N P=0.244N | |POLY 6 | P=0.180N P=0.339N P=0.154N P=0.235N | |LOGISTIC REGRESSION| P=0.173N P=0.310N P=0.133N P=0.229N | |COCH-ARM / FISHERS | P=0.176N P=0.370N P=0.156N P=0.243N | |ORDER RESTRICTED | P=0.151N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 0/47 (0%) 0/44 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/45.00 0/46.38 0/41.53 0/45.07 | |POLY-3 PERCENT (g) | 4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/40 (5%) 0/44 (0%) 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.123N P=0.218N P=0.238N P=0.233N | |POLY 3 | P=0.127N P=0.231N P=0.255N P=0.237N | |POLY 1.5 | P=0.126N P=0.234N P=0.256N P=0.238N | |POLY 6 | P=0.129N P=0.226N P=0.252N P=0.234N | |LOGISTIC REGRESSION| P=0.123N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.125N P=0.247N P=0.264N P=0.247N | |ORDER RESTRICTED | P=0.029N* (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 2/47 (4%) 5/46 (11%) 0/45 (0%) | |POLY-3 RATE (b) | 1/45.35 2/45.93 5/41.58 0/42.08 | |POLY-3 PERCENT (g) | 2.2% 4.4% 12.0% 0.0% | |TERMINAL (d) | 0/40 (0%) 2/43 (5%) 5/38 (13%) 0/38 (0%) | |FIRST INCIDENCE | 673 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.437N P=0.519 P=0.095 P=0.500N | |POLY 3 | P=0.442N P=0.504 P=0.082 P=0.515N | |POLY 1.5 | P=0.443N P=0.500 P=0.084 P=0.516N | |POLY 6 | P=0.438N P=0.509 P=0.083 P=0.513N | |LOGISTIC REGRESSION| P=0.440N P=0.481 P=0.086 P=0.501N | |COCH-ARM / FISHERS | P=0.431N P=0.492 P=0.092 P=0.516N | |ORDER RESTRICTED | P=0.135N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Parotid Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 12/48 (25%) 4/48 (8%) 5/48 (10%) | |POLY-3 RATE (b) | 5/45.43 12/46.93 4/44.36 5/45.08 | |POLY-3 PERCENT (g) | 11.0% 25.6% 9.0% 11.1% | |TERMINAL (d) | 4/40 (10%) 12/44 (27%) 3/40 (8%) 5/41 (12%) | |FIRST INCIDENCE | 647 727 (T) 442 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.244N P=0.082 P=0.505N P=0.617N | |POLY 3 | P=0.242N P=0.060 P=0.515N P=0.625 | |POLY 1.5 | P=0.245N P=0.058 P=0.515N P=0.622 | |POLY 6 | P=0.236N P=0.063 P=0.510N P=0.630N | |LOGISTIC REGRESSION| P=0.244N P=0.067 P=0.481N P=0.631N | |COCH-ARM / FISHERS | P=0.235N P=0.053 P=0.500N P=0.630N | |ORDER RESTRICTED | P=0.198N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Salivary Glands: Submandibular Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 35/48 (73%) 28/48 (58%) 28/48 (58%) 28/48 (58%) | |POLY-3 RATE (b) | 35/46.41 28/46.93 28/44.44 28/45.89 | |POLY-3 PERCENT (g) | 75.4% 59.7% 63.0% 61.0% | |TERMINAL (d) | 32/40 (80%) 28/44 (64%) 26/40 (65%) 24/41 (59%) | |FIRST INCIDENCE | 562 727 (T) 442 626 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.154N P=0.024N* P=0.099N P=0.087N | |POLY 3 | P=0.157N P=0.076N P=0.142N P=0.101N | |POLY 1.5 | P=0.163N P=0.082N P=0.133N P=0.108N | |POLY 6 | P=0.138N P=0.072N P=0.140N P=0.085N | |LOGISTIC REGRESSION| P=0.164N P=0.053N P=0.140N P=0.102N | |COCH-ARM / FISHERS | P=0.136N P=0.098N P=0.098N P=0.098N | |ORDER RESTRICTED | P=0.108N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Spinal Cord: Thoracic, Axon | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/48 (27%) 14/48 (29%) 19/48 (40%) 19/48 (40%) | |POLY-3 RATE (b) | 13/45.46 14/47.49 19/43.66 19/45.09 | |POLY-3 PERCENT (g) | 28.6% 29.5% 43.5% 42.1% | |TERMINAL (d) | 11/40 (28%) 12/44 (27%) 18/40 (45%) 18/41 (44%) | |FIRST INCIDENCE | 676 644 707 723 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.080 P=0.569N P=0.142 P=0.163 | |POLY 3 | P=0.064 P=0.553 P=0.105 P=0.128 | |POLY 1.5 | P=0.066 P=0.533 P=0.110 P=0.127 | |POLY 6 | P=0.063 P=0.576 P=0.106 P=0.133 | |LOGISTIC REGRESSION| P=0.074 P=0.530 P=0.119 P=0.153 | |COCH-ARM / FISHERS | P=0.084 P=0.500 P=0.139 P=0.139 | |ORDER RESTRICTED | P=0.120 (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/47 (19%) 8/47 (17%) 3/45 (7%) 5/47 (11%) | |POLY-3 RATE (b) | 9/45.00 8/46.63 3/42.45 5/45.18 | |POLY-3 PERCENT (g) | 20.0% 17.2% 7.1% 11.1% | |TERMINAL (d) | 7/40 (18%) 7/44 (16%) 3/40 (8%) 3/41 (7%) | |FIRST INCIDENCE | 676 659 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.107N P=0.422N P=0.065N P=0.186N | |POLY 3 | P=0.106N P=0.468N P=0.073N P=0.190N | |POLY 1.5 | P=0.105N P=0.480N P=0.073N P=0.192N | |POLY 6 | P=0.106N P=0.455N P=0.071N P=0.187N | |LOGISTIC REGRESSION| P=0.104N P=0.495N P=0.072N P=0.188N | |COCH-ARM / FISHERS | P=0.102N P=0.500N P=0.070N P=0.193N | |ORDER RESTRICTED | P=0.102N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/47 (13%) 6/47 (13%) 7/45 (16%) 2/47 (4%) | |POLY-3 RATE (b) | 6/44.68 6/46.38 7/42.45 2/45.07 | |POLY-3 PERCENT (g) | 13.4% 12.9% 16.5% 4.4% | |TERMINAL (d) | 6/40 (15%) 6/44 (14%) 7/40 (18%) 2/41 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.114N P=0.553N P=0.500 P=0.126N | |POLY 3 | P=0.116N P=0.594N P=0.460 P=0.130N | |POLY 1.5 | P=0.117N P=0.604N P=0.458 P=0.132N | |POLY 6 | P=0.115N P=0.582N P=0.468 P=0.127N | |LOGISTIC REGRESSION| P=0.114N P=0.553N P=0.500 P=0.126N | |COCH-ARM / FISHERS | P=0.115N P=0.621N P=0.466 P=0.134N | |ORDER RESTRICTED | P=0.113N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 3/47 (6%) 2/46 (4%) 1/48 (2%) | |POLY-3 RATE (b) | 2/45.00 3/46.38 2/43.32 1/45.08 | |POLY-3 PERCENT (g) | 4.4% 6.5% 4.6% 2.2% | |TERMINAL (d) | 2/40 (5%) 3/44 (7%) 2/40 (5%) 1/41 (2%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.308N P=0.544 P=0.695 P=0.491N | |POLY 3 | P=0.311N P=0.514 P=0.680 P=0.499N | |POLY 1.5 | P=0.311N P=0.508 P=0.680 P=0.500N | |POLY 6 | P=0.308N P=0.522 P=0.684 P=0.495N | |LOGISTIC REGRESSION| P=0.308N P=0.544 P=0.695 P=0.491N | |COCH-ARM / FISHERS | P=0.299N P=0.500 P=0.683 P=0.492N | |ORDER RESTRICTED | P=0.363N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 2/47 (4%) 1/46 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 2/45.29 2/46.38 1/43.32 0/45.08 | |POLY-3 PERCENT (g) | 4.4% 4.3% 2.3% 0.0% | |TERMINAL (d) | 1/40 (3%) 2/44 (5%) 1/40 (3%) 0/41 (0%) | |FIRST INCIDENCE | 647 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.126N P=0.665N P=0.505N P=0.239N | |POLY 3 | P=0.127N P=0.685N P=0.516N P=0.238N | |POLY 1.5 | P=0.127N P=0.689N P=0.515N P=0.238N | |POLY 6 | P=0.127N P=0.680N P=0.514N P=0.237N | |LOGISTIC REGRESSION| P=0.119N P=0.646 P=0.498N P=0.214N | |COCH-ARM / FISHERS | P=0.121N P=0.692N P=0.508N P=0.242N | |ORDER RESTRICTED | P=0.156N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/47 (23%) 8/47 (17%) 4/46 (9%) 7/48 (15%) | |POLY-3 RATE (b) | 11/45.00 8/46.44 4/43.32 7/45.99 | |POLY-3 PERCENT (g) | 24.5% 17.2% 9.2% 15.2% | |TERMINAL (d) | 11/40 (28%) 7/44 (16%) 4/40 (10%) 6/41 (15%) | |FIRST INCIDENCE | 727 (T) 711 727 (T) 318 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.163N P=0.228N P=0.044N* P=0.200N | |POLY 3 | P=0.155N P=0.278N P=0.051N P=0.200N | |POLY 1.5 | P=0.156N P=0.290N P=0.051N P=0.206N | |POLY 6 | P=0.152N P=0.260N P=0.048N* P=0.191N | |LOGISTIC REGRESSION| P=0.151N P=0.230N P=0.044N* P=0.194N | |COCH-ARM / FISHERS | P=0.148N P=0.304N P=0.049N* P=0.202N | |ORDER RESTRICTED | P=0.090N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/43 (9%) 2/44 (5%) 3/43 (7%) 3/47 (6%) | |POLY-3 RATE (b) | 4/41.73 2/43.38 3/40.21 3/44.42 | |POLY-3 PERCENT (g) | 9.6% 4.6% 7.5% 6.8% | |TERMINAL (d) | 3/37 (8%) 2/41 (5%) 2/37 (5%) 2/40 (5%) | |FIRST INCIDENCE | 599 727 (T) 442 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.496N P=0.298N P=0.509N P=0.470N | |POLY 3 | P=0.484N P=0.319N P=0.520N P=0.466N | |POLY 1.5 | P=0.482N P=0.323N P=0.518N P=0.466N | |POLY 6 | P=0.483N P=0.315N P=0.517N P=0.462N | |LOGISTIC REGRESSION| P=0.417N P=0.395N P=0.422N P=0.431N | |COCH-ARM / FISHERS | P=0.465N P=0.327N P=0.500N P=0.450N | |ORDER RESTRICTED | P=0.432N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Thymus | | Ectopic Parathyroid Gland | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/43 (7%) 1/44 (2%) 2/43 (5%) 3/47 (6%) | |POLY-3 RATE (b) | 3/41.29 1/43.38 2/39.44 3/44.08 | |POLY-3 PERCENT (g) | 7.3% 2.3% 5.1% 6.8% | |TERMINAL (d) | 3/37 (8%) 1/41 (2%) 2/37 (5%) 3/40 (8%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.483 P=0.269N P=0.500N P=0.627N | |POLY 3 | P=0.483 P=0.288N P=0.521N P=0.632N | |POLY 1.5 | P=0.486 P=0.292N P=0.519N P=0.632N | |POLY 6 | P=0.483 P=0.282N P=0.518N P=0.628N | |LOGISTIC REGRESSION| P=0.483 P=0.269N P=0.500N P=0.627N | |COCH-ARM / FISHERS | P=0.503 P=0.299N P=0.500N P=0.618N | |ORDER RESTRICTED | P=0.475N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/43 (7%) 5/44 (11%) 6/43 (14%) 2/47 (4%) | |POLY-3 RATE (b) | 3/41.29 5/43.38 6/39.44 2/44.08 | |POLY-3 PERCENT (g) | 7.3% 11.5% 15.2% 4.5% | |TERMINAL (d) | 3/37 (8%) 5/41 (12%) 6/37 (16%) 2/40 (5%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.332N P=0.413 P=0.240 P=0.464N | |POLY 3 | P=0.333N P=0.384 P=0.218 P=0.470N | |POLY 1.5 | P=0.332N P=0.377 P=0.221 P=0.471N | |POLY 6 | P=0.330N P=0.393 P=0.221 P=0.467N | |LOGISTIC REGRESSION| P=0.332N P=0.413 P=0.240 P=0.464N | |COCH-ARM / FISHERS | P=0.310N P=0.370 P=0.242 P=0.457N | |ORDER RESTRICTED | P=0.225N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland | | Ultimobranchial Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/46 (0%) 2/46 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 0/44.14 0/45.38 2/43.84 2/45.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 4.4% | |TERMINAL (d) | 0/39 (0%) 0/43 (0%) 1/40 (3%) 2/41 (5%) | |FIRST INCIDENCE | --- --- 568 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.084 (e) P=0.238 P=0.249 | |POLY 3 | P=0.083 (e) P=0.236 P=0.242 | |POLY 1.5 | P=0.083 (e) P=0.233 P=0.240 | |POLY 6 | P=0.084 (e) P=0.240 P=0.245 | |LOGISTIC REGRESSION| P=0.094 (e) P=0.251 P=0.249 | |COCH-ARM / FISHERS | P=0.087 (e) P=0.242 P=0.253 | |ORDER RESTRICTED | P=0.115 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 2/46 (4%) 3/46 (7%) 1/48 (2%) | |POLY-3 RATE (b) | 2/44.14 2/45.38 3/43.52 1/45.17 | |POLY-3 PERCENT (g) | 4.5% 4.4% 6.9% 2.2% | |TERMINAL (d) | 2/39 (5%) 2/43 (5%) 2/40 (5%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 673 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399N P=0.659N P=0.507 P=0.480N | |POLY 3 | P=0.402N P=0.684N P=0.494 P=0.492N | |POLY 1.5 | P=0.403N P=0.690N P=0.490 P=0.495N | |POLY 6 | P=0.397N P=0.676N P=0.502 P=0.486N | |LOGISTIC REGRESSION| P=0.400N P=0.659N P=0.490 P=0.492N | |COCH-ARM / FISHERS | P=0.394N P=0.683 P=0.490 P=0.492N | |ORDER RESTRICTED | P=0.389N (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Tongue: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/45.14 0/46.93 0/43.58 0/45.08 | |POLY-3 PERCENT (g) | 4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/40 (5%) 0/44 (0%) 0/40 (0%) 0/41 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.123N P=0.218N P=0.238N P=0.233N | |POLY 3 | P=0.126N P=0.229N P=0.245N P=0.237N | |POLY 1.5 | P=0.125N P=0.232N P=0.244N P=0.239N | |POLY 6 | P=0.128N P=0.225N P=0.243N P=0.234N | |LOGISTIC REGRESSION| P=0.123N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.122N P=0.247N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.029N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Inclusion Body Intracytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/47 (15%) 15/46 (33%) 34/45 (76%) 39/48 (81%) | |POLY-3 RATE (b) | 7/45.00 15/45.38 34/43.09 39/45.08 | |POLY-3 PERCENT (g) | 15.6% 33.1% 78.9% 86.5% | |TERMINAL (d) | 7/40 (18%) 15/43 (35%) 33/39 (85%) 39/41 (95%) | |FIRST INCIDENCE | 727 (T) 727 (T) 442 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.062 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.043 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.040 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.048 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.062 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.038 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/19/03 EXPERIMENT: 93005 TEST: 04 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(C57BL/6NXC3H/HEN MTN-NCTR) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/47 (77%) 34/46 (74%) 33/45 (73%) 25/48 (52%) | |POLY-3 RATE (b) | 36/45.94 34/45.38 33/43.04 25/45.65 | |POLY-3 PERCENT (g) | 78.4% 74.9% 76.7% 54.8% | |TERMINAL (d) | 33/40 (83%) 34/43 (79%) 31/39 (80%) 23/41 (56%) | |FIRST INCIDENCE | 599 727 (T) 568 626 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007N** P=0.194N P=0.397N P=0.012N* | |POLY 3 | P=0.006N** P=0.444N P=0.525N P=0.012N* | |POLY 1.5 | P=0.006N** P=0.457N P=0.520N P=0.013N* | |POLY 6 | P=0.005N** P=0.426N P=0.505N P=0.010N* | |LOGISTIC REGRESSION| P=0.007N** P=0.315N P=0.530N P=0.014N* | |COCH-ARM / FISHERS | P=0.004N** P=0.476N P=0.452N P=0.011N* | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 225 PPM 450 PPM | | | | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 42/48 (88%) 46/48 (96%) 44/47 (94%) 42/48 (88%) | |POLY-3 RATE (b) | 42/45.97 46/47.94 44/46.10 42/45.38 | |POLY-3 PERCENT (g) | 91.4% 96.0% 95.5% 92.6% | |TERMINAL (d) | 39/40 (98%) 43/44 (98%) 39/40 (98%) 40/41 (98%) | |FIRST INCIDENCE | 599 596 226 673 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.459N P=0.635N P=0.362 P=0.498N | |POLY 3 | P=0.584N P=0.298 P=0.342 P=0.576 | |POLY 1.5 | P=0.563N P=0.218 P=0.296 P=0.552 | |POLY 6 | P=0.579N P=0.422 P=0.429 P=0.634 | |LOGISTIC REGRESSION| P=0.567 P=0.301 P=0.152 P=0.586N | |COCH-ARM / FISHERS | P=0.398N P=0.134 P=0.254 P=0.621N | |ORDER RESTRICTED | P=0.382 (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).