TDMS Study 93005-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR MALACHITE GREEN DATE: 05/05/03 EXPERIMENT: 93005 TEST: 03 TIME: 15:11:48 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93005 PATHOLOGIST: MELLICK, PAUL CAS: 569-64-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF MALACHITE GREEN =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Angiectasis Atrophy Bone Marrow: Myeloid Cell Hyperplasia Bone: Turbinate Osteopetrosis Brain: Hypothalamus Compression Clitoral Gland Inflammation Eye Cataract Eye: Retina Degeneration Heart Cardiomyopathy Liver Eosinophilic Focus Infiltration Cellular Lymphocyte Liver: Centrilobular Necrosis Lung Foreign Body Hemorrhage Inflammation Chronic Focal Lymph Node, Mesenteric Hyperplasia Lymphoid Lymph Node: Lumbar Ectasia Mammary Gland: Duct Dilatation Nose: Nasolacrimal Duct Inflammation Ovary Atrophy Cyst Pituitary Gland: Pars Distalis Hyperplasia Skin Hyperkeratosis Spleen Hematopoietic Cell Proliferation Thyroid Gland: Follicle Cyst Vagina Prolapse =============================================================== Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/48 (21%) 11/48 (23%) 17/48 (35%) 16/48 (33%) | |POLY-3 RATE (b) | 10/40.15 11/38.79 17/44.28 16/38.40 | |POLY-3 PERCENT (g) | 24.9% 28.4% 38.4% 41.7% | |TERMINAL (d) | 9/29 (31%) 9/23 (39%) 14/32 (44%) 11/25 (44%) | |FIRST INCIDENCE | 704 591 627 619 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.043 * P=0.283 P=0.146 P=0.056 | |POLY 3 | P=0.048 * P=0.463 P=0.134 P=0.085 | |POLY 1.5 | P=0.049 * P=0.481 P=0.112 P=0.094 | |POLY 6 | P=0.051 P=0.434 P=0.164 P=0.080 | |LOGISTIC REGRESSION| P=0.037 * P=0.378 P=0.152 P=0.058 | |COCH-ARM / FISHERS | P=0.066 P=0.500 P=0.086 P=0.125 | |ORDER RESTRICTED | P=0.086 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 0/43.37 2/37.30 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | --- --- --- 697 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.037 * (e) (e) P=0.206 | |POLY 3 | P=0.042 * (e) (e) P=0.221 | |POLY 1.5 | P=0.042 * (e) (e) P=0.225 | |POLY 6 | P=0.043 * (e) (e) P=0.216 | |LOGISTIC REGRESSION| P=0.038 * (e) (e) P=0.213 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.024 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 4/48 (8%) 1/48 (2%) 4/48 (8%) | |POLY-3 RATE (b) | 1/40.06 4/38.24 1/43.37 4/37.56 | |POLY-3 PERCENT (g) | 2.5% 10.5% 2.3% 10.7% | |TERMINAL (d) | 1/29 (3%) 4/23 (17%) 1/32 (3%) 3/25 (12%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 619 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.243 P=0.113 P=0.740N P=0.142 | |POLY 3 | P=0.248 P=0.163 P=0.743N P=0.158 | |POLY 1.5 | P=0.250 P=0.171 P=0.750N P=0.164 | |POLY 6 | P=0.246 P=0.152 P=0.736N P=0.152 | |LOGISTIC REGRESSION| P=0.233 P=0.113 P=0.740N P=0.151 | |COCH-ARM / FISHERS | P=0.262 P=0.181 P=0.753N P=0.181 | |ORDER RESTRICTED | P=0.108 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/48 (13%) 5/48 (10%) 2/48 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 6/40.41 5/39.42 2/43.58 3/37.31 | |POLY-3 PERCENT (g) | 14.9% 12.7% 4.6% 8.0% | |TERMINAL (d) | 3/29 (10%) 2/23 (9%) 1/32 (3%) 2/25 (8%) | |FIRST INCIDENCE | 667 485 673 694 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.160N P=0.609N P=0.110N P=0.328N | |POLY 3 | P=0.145N P=0.518N P=0.108N P=0.280N | |POLY 1.5 | P=0.146N P=0.508N P=0.118N P=0.269N | |POLY 6 | P=0.143N P=0.534N P=0.100N P=0.295N | |LOGISTIC REGRESSION| P=0.148N P=0.519N P=0.104N P=0.296N | |COCH-ARM / FISHERS | P=0.139N P=0.500N P=0.134N P=0.243N | |ORDER RESTRICTED | P=0.161N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 3/47 (6%) 1/48 (2%) 1/48 (2%) | |POLY-3 RATE (b) | 1/39.06 3/37.78 1/43.37 1/37.18 | |POLY-3 PERCENT (g) | 2.6% 7.9% 2.3% 2.7% | |TERMINAL (d) | 1/28 (4%) 2/23 (9%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 728 (T) 718 728 (T) 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.400N P=0.243 P=0.732N P=0.737 | |POLY 3 | P=0.395N P=0.292 P=0.737N P=0.750 | |POLY 1.5 | P=0.394N P=0.299 P=0.744N P=0.754 | |POLY 6 | P=0.396N P=0.283 P=0.729N P=0.745 | |LOGISTIC REGRESSION| P=0.409N P=0.262 P=0.732N P=0.737 | |COCH-ARM / FISHERS | P=0.384N P=0.308 P=0.747N P=0.747N | |ORDER RESTRICTED | P=0.429N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone Marrow | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 3/48 (6%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 1/40.06 3/38.79 2/43.37 2/38.29 | |POLY-3 PERCENT (g) | 2.5% 7.7% 4.6% 5.2% | |TERMINAL (d) | 1/29 (3%) 1/23 (4%) 2/32 (6%) 0/25 (0%) | |FIRST INCIDENCE | 728 (T) 574 728 (T) 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.511 P=0.256 P=0.535 P=0.464 | |POLY 3 | P=0.516 P=0.293 P=0.528 P=0.484 | |POLY 1.5 | P=0.517 P=0.299 P=0.517 P=0.487 | |POLY 6 | P=0.515 P=0.284 P=0.539 P=0.481 | |LOGISTIC REGRESSION| P=0.546 P=0.294 P=0.535 P=0.560 | |COCH-ARM / FISHERS | P=0.531 P=0.308 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.402 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone Marrow | | Myelofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 2/43.58 0/37.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 673 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.555 (e) P=0.270 (e) | |POLY 3 | P=0.515 (e) P=0.256 (e) | |POLY 1.5 | P=0.528 (e) P=0.249 (e) | |POLY 6 | P=0.502 (e) P=0.265 (e) | |LOGISTIC REGRESSION| P=0.554 (e) P=0.248 (e) | |COCH-ARM / FISHERS | P=0.562 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.265 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 0/48 (0%) 5/48 (10%) 4/48 (8%) | |POLY-3 RATE (b) | 5/40.83 0/38.24 5/44.08 4/38.06 | |POLY-3 PERCENT (g) | 12.3% 0.0% 11.3% 10.5% | |TERMINAL (d) | 4/29 (14%) 0/23 (0%) 4/32 (13%) 2/25 (8%) | |FIRST INCIDENCE | 443 --- 484 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.354 P=0.051N P=0.576N P=0.578N | |POLY 3 | P=0.370 P=0.035N* P=0.582N P=0.544N | |POLY 1.5 | P=0.367 P=0.033N* P=0.601N P=0.532N | |POLY 6 | P=0.377 P=0.039N* P=0.562N P=0.557N | |LOGISTIC REGRESSION| P=0.386 P=0.033N* P=0.594 P=0.501N | |COCH-ARM / FISHERS | P=0.381 P=0.028N* P=0.630N P=0.500N | |ORDER RESTRICTED | P=0.361N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone: Femur | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 1/48 (2%) 0/48 (0%) 3/48 (6%) | |POLY-3 RATE (b) | 1/40.06 1/38.65 0/43.37 3/37.99 | |POLY-3 PERCENT (g) | 2.5% 2.6% 0.0% 7.9% | |TERMINAL (d) | 1/29 (3%) 0/23 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | 728 (T) 610 --- 589 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.153 P=0.722 P=0.480N P=0.268 | |POLY 3 | P=0.161 P=0.753 P=0.484N P=0.286 | |POLY 1.5 | P=0.159 P=0.757 P=0.490N P=0.290 | |POLY 6 | P=0.164 P=0.747 P=0.478N P=0.282 | |LOGISTIC REGRESSION| P=0.171 P=0.762N (e) P=0.297 | |COCH-ARM / FISHERS | P=0.161 P=0.753N P=0.500N P=0.308 | |ORDER RESTRICTED | P=0.088 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/48 (17%) 3/48 (6%) 3/48 (6%) 3/48 (6%) | |POLY-3 RATE (b) | 8/40.99 3/38.69 3/43.43 3/37.72 | |POLY-3 PERCENT (g) | 19.5% 7.8% 6.9% 8.0% | |TERMINAL (d) | 5/29 (17%) 2/23 (9%) 2/32 (6%) 2/25 (8%) | |FIRST INCIDENCE | 529 596 715 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.122N P=0.172N P=0.078N P=0.150N | |POLY 3 | P=0.110N P=0.114N P=0.079N P=0.123N | |POLY 1.5 | P=0.113N P=0.106N P=0.086N P=0.116N | |POLY 6 | P=0.106N P=0.127N P=0.073N P=0.133N | |LOGISTIC REGRESSION| P=0.118N P=0.110N P=0.081N P=0.116N | |COCH-ARM / FISHERS | P=0.111N P=0.099N P=0.099N P=0.099N | |ORDER RESTRICTED | P=0.060N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone: Sternum | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/48 (17%) 3/48 (6%) 3/48 (6%) 3/48 (6%) | |POLY-3 RATE (b) | 8/40.99 3/38.69 3/43.43 3/37.72 | |POLY-3 PERCENT (g) | 19.5% 7.8% 6.9% 8.0% | |TERMINAL (d) | 5/29 (17%) 2/23 (9%) 2/32 (6%) 2/25 (8%) | |FIRST INCIDENCE | 529 596 715 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.122N P=0.172N P=0.078N P=0.150N | |POLY 3 | P=0.110N P=0.114N P=0.079N P=0.123N | |POLY 1.5 | P=0.113N P=0.106N P=0.086N P=0.116N | |POLY 6 | P=0.106N P=0.127N P=0.073N P=0.133N | |LOGISTIC REGRESSION| P=0.118N P=0.110N P=0.081N P=0.116N | |COCH-ARM / FISHERS | P=0.111N P=0.099N P=0.099N P=0.099N | |ORDER RESTRICTED | P=0.060N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Bone: Turbinate | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/48 (15%) 2/48 (4%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 7/40.99 2/38.69 2/43.43 2/37.72 | |POLY-3 PERCENT (g) | 17.1% 5.2% 4.6% 5.3% | |TERMINAL (d) | 4/29 (14%) 1/23 (4%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 529 596 715 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.092N P=0.134N P=0.065N P=0.119N | |POLY 3 | P=0.080N P=0.091N P=0.064N P=0.098N | |POLY 1.5 | P=0.083N P=0.085N P=0.070N P=0.092N | |POLY 6 | P=0.076N P=0.101N P=0.060N P=0.105N | |LOGISTIC REGRESSION| P=0.086N P=0.084N P=0.071N P=0.088N | |COCH-ARM / FISHERS | P=0.084N P=0.079N P=0.079N P=0.079N | |ORDER RESTRICTED | P=0.033N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Brain: Hypothalamus | | Compression | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 14/48 (29%) 10/48 (21%) 7/48 (15%) | |POLY-3 RATE (b) | 5/40.94 14/41.88 10/45.35 7/37.48 | |POLY-3 PERCENT (g) | 12.2% 33.4% 22.1% 18.7% | |TERMINAL (d) | 1/29 (3%) 4/23 (17%) 2/32 (6%) 5/25 (20%) | |FIRST INCIDENCE | 606 485 603 685 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.463N P=0.015 * P=0.213 P=0.289 | |POLY 3 | P=0.499N P=0.018 * P=0.179 P=0.316 | |POLY 1.5 | P=0.478N P=0.018 * P=0.158 P=0.336 | |POLY 6 | P=0.521N P=0.018 * P=0.206 P=0.292 | |LOGISTIC REGRESSION| P=0.422N P=0.022 * P=0.101 P=0.321 | |COCH-ARM / FISHERS | P=0.420N P=0.019 * P=0.130 P=0.379 | |ORDER RESTRICTED | P=0.140 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 4/48 (8%) 2/47 (4%) 6/47 (13%) | |POLY-3 RATE (b) | 5/40.12 4/38.77 2/42.50 6/36.99 | |POLY-3 PERCENT (g) | 12.5% 10.3% 4.7% 16.2% | |TERMINAL (d) | 4/29 (14%) 2/23 (9%) 1/31 (3%) 5/25 (20%) | |FIRST INCIDENCE | 711 598 697 605 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.378 P=0.618N P=0.189N P=0.396 | |POLY 3 | P=0.389 P=0.522N P=0.192N P=0.442 | |POLY 1.5 | P=0.386 P=0.511N P=0.205N P=0.452 | |POLY 6 | P=0.395 P=0.538N P=0.180N P=0.432 | |LOGISTIC REGRESSION| P=0.370 P=0.553N P=0.176N P=0.413 | |COCH-ARM / FISHERS | P=0.397 P=0.500N P=0.226N P=0.485 | |ORDER RESTRICTED | P=0.250 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/48 (44%) 30/48 (63%) 23/47 (49%) 26/47 (55%) | |POLY-3 RATE (b) | 21/43.51 30/43.08 23/44.45 26/39.79 | |POLY-3 PERCENT (g) | 48.3% 69.6% 51.8% 65.3% | |TERMINAL (d) | 12/29 (41%) 17/23 (74%) 15/31 (48%) 17/25 (68%) | |FIRST INCIDENCE | 443 494 508 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.344 P=0.019 * P=0.565 P=0.105 | |POLY 3 | P=0.232 P=0.029 * P=0.454 P=0.081 | |POLY 1.5 | P=0.260 P=0.036 * P=0.426 P=0.103 | |POLY 6 | P=0.211 P=0.023 * P=0.482 P=0.063 | |LOGISTIC REGRESSION| P=0.301 P=0.043 * P=0.400 P=0.120 | |COCH-ARM / FISHERS | P=0.361 P=0.051 P=0.382 P=0.178 | |ORDER RESTRICTED | P=0.078 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/48 (13%) 5/48 (10%) 7/47 (15%) 6/47 (13%) | |POLY-3 RATE (b) | 6/40.98 5/39.93 7/43.61 6/37.61 | |POLY-3 PERCENT (g) | 14.6% 12.5% 16.1% 16.0% | |TERMINAL (d) | 4/29 (14%) 1/23 (4%) 3/31 (10%) 3/25 (12%) | |FIRST INCIDENCE | 533 540 603 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.453 P=0.600N P=0.575 P=0.528 | |POLY 3 | P=0.426 P=0.518N P=0.548 P=0.560 | |POLY 1.5 | P=0.431 P=0.510N P=0.523 P=0.571 | |POLY 6 | P=0.426 P=0.531N P=0.577 P=0.550 | |LOGISTIC REGRESSION| P=0.469 P=0.487N P=0.456 P=0.581 | |COCH-ARM / FISHERS | P=0.462 P=0.500N P=0.483 P=0.605 | |ORDER RESTRICTED | P=0.599 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/47 (17%) 3/48 (6%) 2/48 (4%) 9/48 (19%) | |POLY-3 RATE (b) | 8/40.16 3/38.82 2/43.43 9/38.66 | |POLY-3 PERCENT (g) | 19.9% 7.7% 4.6% 23.3% | |TERMINAL (d) | 6/29 (21%) 1/23 (4%) 1/32 (3%) 5/25 (20%) | |FIRST INCIDENCE | 589 577 715 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.231 P=0.171N P=0.035N* P=0.383 | |POLY 3 | P=0.270 P=0.105N P=0.032N* P=0.465 | |POLY 1.5 | P=0.263 P=0.099N P=0.035N* P=0.478 | |POLY 6 | P=0.279 P=0.117N P=0.029N* P=0.449 | |LOGISTIC REGRESSION| P=0.243 P=0.111N P=0.031N* P=0.455 | |COCH-ARM / FISHERS | P=0.269 P=0.093N P=0.042N* P=0.519 | |ORDER RESTRICTED | P=0.074 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Eye | | Phthisis Bulbi | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/39.62 0/38.24 2/43.58 0/37.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 673 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.555 (e) P=0.270 (e) | |POLY 3 | P=0.515 (e) P=0.259 (e) | |POLY 1.5 | P=0.530 (e) P=0.252 (e) | |POLY 6 | P=0.499 (e) P=0.266 (e) | |LOGISTIC REGRESSION| P=0.556 (e) P=0.251 (e) | |COCH-ARM / FISHERS | P=0.565 (e) P=0.253 (e) | |ORDER RESTRICTED | P=0.268 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Eye: Bilateral | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 1/48 (2%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 1/39.62 1/38.32 2/43.43 2/37.76 | |POLY-3 PERCENT (g) | 2.5% 2.6% 4.6% 5.3% | |TERMINAL (d) | 1/29 (3%) 0/23 (0%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | 728 (T) 707 715 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.305 P=0.723 P=0.537 P=0.468 | |POLY 3 | P=0.313 P=0.754 P=0.532 P=0.483 | |POLY 1.5 | P=0.316 P=0.759 P=0.523 P=0.490 | |POLY 6 | P=0.311 P=0.745 P=0.541 P=0.476 | |LOGISTIC REGRESSION| P=0.315 P=0.740 P=0.543 P=0.504 | |COCH-ARM / FISHERS | P=0.330 P=0.747N P=0.508 P=0.508 | |ORDER RESTRICTED | P=0.420 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Eye: Bilateral, Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/46 (28%) 14/44 (32%) 20/48 (42%) 18/46 (39%) | |POLY-3 RATE (b) | 13/39.47 14/37.26 20/45.62 18/37.73 | |POLY-3 PERCENT (g) | 32.9% 37.6% 43.8% 47.7% | |TERMINAL (d) | 10/29 (35%) 8/22 (36%) 12/32 (38%) 14/25 (56%) | |FIRST INCIDENCE | 626 598 508 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.099 P=0.253 P=0.202 P=0.082 | |POLY 3 | P=0.098 P=0.426 P=0.208 P=0.132 | |POLY 1.5 | P=0.104 P=0.437 P=0.172 P=0.147 | |POLY 6 | P=0.090 P=0.407 P=0.255 P=0.111 | |LOGISTIC REGRESSION| P=0.103 P=0.378 P=0.166 P=0.115 | |COCH-ARM / FISHERS | P=0.132 P=0.445 P=0.126 P=0.189 | |ORDER RESTRICTED | P=0.144 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Eye: Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/46 (46%) 22/44 (50%) 29/48 (60%) 27/46 (59%) | |POLY-3 RATE (b) | 21/40.43 22/38.22 29/45.96 27/39.07 | |POLY-3 PERCENT (g) | 51.9% 57.6% 63.1% 69.1% | |TERMINAL (d) | 16/29 (55%) 13/22 (59%) 19/32 (59%) 19/25 (76%) | |FIRST INCIDENCE | 535 591 508 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.073 P=0.179 P=0.216 P=0.048 * | |POLY 3 | P=0.060 P=0.389 P=0.198 P=0.080 | |POLY 1.5 | P=0.066 P=0.406 P=0.157 P=0.096 | |POLY 6 | P=0.056 P=0.365 P=0.252 P=0.064 | |LOGISTIC REGRESSION| P=0.066 P=0.342 P=0.173 P=0.076 | |COCH-ARM / FISHERS | P=0.100 P=0.420 P=0.110 P=0.148 | |ORDER RESTRICTED | P=0.081 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/47 (72%) 37/48 (77%) 36/48 (75%) 32/48 (67%) | |POLY-3 RATE (b) | 34/44.20 37/44.54 36/45.93 32/42.56 | |POLY-3 PERCENT (g) | 76.9% 83.1% 78.4% 75.2% | |TERMINAL (d) | 23/29 (79%) 19/23 (83%) 28/32 (88%) 20/25 (80%) | |FIRST INCIDENCE | 443 494 484 111 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.405N P=0.089 P=0.453N P=0.413 | |POLY 3 | P=0.345N P=0.314 P=0.537 P=0.526N | |POLY 1.5 | P=0.298N P=0.343 P=0.520 P=0.460N | |POLY 6 | P=0.405N P=0.289 P=0.534 P=0.599N | |LOGISTIC REGRESSION| P=0.306N P=0.325 P=0.589 P=0.458N | |COCH-ARM / FISHERS | P=0.221N P=0.384 P=0.475 P=0.353N | |ORDER RESTRICTED | P=0.448N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/48 (27%) 22/48 (46%) 19/48 (40%) 14/48 (29%) | |POLY-3 RATE (b) | 13/42.79 22/41.64 19/44.70 14/39.34 | |POLY-3 PERCENT (g) | 30.4% 52.8% 42.5% 35.6% | |TERMINAL (d) | 8/29 (28%) 11/23 (48%) 16/32 (50%) 9/25 (36%) | |FIRST INCIDENCE | 443 485 508 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.420N P=0.021 * P=0.235 P=0.361 | |POLY 3 | P=0.468N P=0.026 * P=0.167 P=0.394 | |POLY 1.5 | P=0.441N P=0.032 * P=0.157 P=0.424 | |POLY 6 | P=0.491N P=0.020 * P=0.175 P=0.367 | |LOGISTIC REGRESSION| P=0.394N P=0.043 * P=0.136 P=0.473 | |COCH-ARM / FISHERS | P=0.359N P=0.045 * P=0.139 P=0.500 | |ORDER RESTRICTED | P=0.164 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/48 (69%) 31/48 (65%) 30/48 (63%) 30/48 (63%) | |POLY-3 RATE (b) | 33/48.00 31/47.89 30/47.64 30/46.78 | |POLY-3 PERCENT (g) | 68.8% 64.7% 63.0% 64.1% | |TERMINAL (d) | 14/29 (48%) 9/23 (39%) 15/32 (47%) 9/25 (36%) | |FIRST INCIDENCE | 401 443 484 323 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.444N P=0.441 P=0.224N P=0.526 | |POLY 3 | P=0.376N P=0.421N P=0.353N P=0.399N | |POLY 1.5 | P=0.368N P=0.418N P=0.345N P=0.390N | |POLY 6 | P=0.385N P=0.426N P=0.365N P=0.408N | |LOGISTIC REGRESSION| P=0.224N P=0.158N P=0.501N P=0.210N | |COCH-ARM / FISHERS | P=0.311N P=0.414N P=0.334N P=0.334N | |ORDER RESTRICTED | P=0.471N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 39/48 (81%) 38/48 (79%) 41/48 (85%) 40/48 (83%) | |POLY-3 RATE (b) | 39/43.94 38/43.96 41/46.27 40/42.50 | |POLY-3 PERCENT (g) | 88.8% 86.5% 88.6% 94.1% | |TERMINAL (d) | 27/29 (93%) 23/23 (100%) 28/32 (88%) 25/25 (100%) | |FIRST INCIDENCE | 526 485 603 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.285 P=0.175 P=0.405N P=0.163 | |POLY 3 | P=0.164 P=0.497N P=0.632N P=0.267 | |POLY 1.5 | P=0.192 P=0.488N P=0.539 P=0.321 | |POLY 6 | P=0.171 P=0.542N P=0.521N P=0.238 | |LOGISTIC REGRESSION| P=0.168 P=0.608 P=0.476N P=0.193 | |COCH-ARM / FISHERS | P=0.355 P=0.500N P=0.392 P=0.500 | |ORDER RESTRICTED | P=0.206 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lacrimal Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/18 (11%) 2/14 (14%) 2/15 (13%) 3/9 (33%) | |POLY-3 RATE (b) | 2/16.29 2/12.59 2/13.08 3/8.31 | |POLY-3 PERCENT (g) | 12.3% 15.9% 15.3% 36.1% | |TERMINAL (d) | 1/12 (8%) 2/8 (25%) 2/8 (25%) 3/7 (43%) | |FIRST INCIDENCE | 722 728 (T) 728 (T) 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.199 P=0.556 P=0.590 P=0.286 | |POLY 3 | P=0.135 P=0.602 P=0.617 P=0.193 | |POLY 1.5 | P=0.137 P=0.602 P=0.623 P=0.191 | |POLY 6 | P=0.133 P=0.601 P=0.603 P=0.195 | |LOGISTIC REGRESSION| P=0.148 P=0.578 P=0.540 P=0.213 | |COCH-ARM / FISHERS | P=0.135 P=0.597 P=0.626 P=0.189 | |ORDER RESTRICTED | P=0.152 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lacrimal Gland | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/18 (100%) 14/14 (100%) 15/15 (100%) 9/9 (100%) | |POLY-3 RATE (b) | 18/18.00 14/14.00 15/15.00 9/9.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 12/12 (100%) 8/8 (100%) 8/8 (100%) 7/7 (100%) | |FIRST INCIDENCE | 626 574 603 630 | |-------------------| | |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 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/48 (44%) 17/48 (35%) 20/48 (42%) 15/48 (31%) | |POLY-3 RATE (b) | 21/41.30 17/39.60 20/44.91 15/38.70 | |POLY-3 PERCENT (g) | 50.9% 42.9% 44.5% 38.8% | |TERMINAL (d) | 19/29 (66%) 14/23 (61%) 16/32 (50%) 10/25 (40%) | |FIRST INCIDENCE | 443 494 484 570 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.213N P=0.590N P=0.333N P=0.290N | |POLY 3 | P=0.199N P=0.306N P=0.353N P=0.187N | |POLY 1.5 | P=0.209N P=0.284N P=0.412N P=0.181N | |POLY 6 | P=0.172N P=0.347N P=0.287N P=0.185N | |LOGISTIC REGRESSION| P=0.217N P=0.352N P=0.360N P=0.220N | |COCH-ARM / FISHERS | P=0.182N P=0.266N P=0.500N P=0.146N | |ORDER RESTRICTED | P=0.213N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 1/48 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 0/40.06 2/38.24 1/43.37 0/37.18 | |POLY-3 PERCENT (g) | 0.0% 5.2% 2.3% 0.0% | |TERMINAL (d) | 0/29 (0%) 2/23 (9%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407N P=0.188 P=0.520 (e) | |POLY 3 | P=0.418N P=0.226 P=0.516 (e) | |POLY 1.5 | P=0.413N P=0.232 P=0.510 (e) | |POLY 6 | P=0.425N P=0.218 P=0.522 (e) | |LOGISTIC REGRESSION| (e) P=0.188 P=0.520 (e) | |COCH-ARM / FISHERS | P=0.400N P=0.247 P=0.500 (e) | |ORDER RESTRICTED | P=0.330N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Developmental Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 7/48 (15%) 2/48 (4%) 5/48 (10%) | |POLY-3 RATE (b) | 4/40.69 7/38.94 2/43.66 5/38.35 | |POLY-3 PERCENT (g) | 9.8% 18.0% 4.6% 13.0% | |TERMINAL (d) | 2/29 (7%) 4/23 (17%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | 552 539 666 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.513N P=0.180 P=0.292N P=0.428 | |POLY 3 | P=0.488N P=0.233 P=0.305N P=0.463 | |POLY 1.5 | P=0.490N P=0.246 P=0.317N P=0.471 | |POLY 6 | P=0.484N P=0.213 P=0.292N P=0.454 | |LOGISTIC REGRESSION| P=0.491N P=0.239 P=0.344N P=0.492 | |COCH-ARM / FISHERS | P=0.478N P=0.262 P=0.339N P=0.500 | |ORDER RESTRICTED | P=0.364N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 10/48 (21%) 13/48 (27%) 14/48 (29%) | |POLY-3 RATE (b) | 5/40.06 10/39.98 13/44.47 14/38.08 | |POLY-3 PERCENT (g) | 12.5% 25.0% 29.2% 36.8% | |TERMINAL (d) | 5/29 (17%) 6/23 (26%) 8/32 (25%) 11/25 (44%) | |FIRST INCIDENCE | 728 (T) 556 626 605 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017 * P=0.067 P=0.063 P=0.007 ** | |POLY 3 | P=0.013 * P=0.122 P=0.051 P=0.010 * | |POLY 1.5 | P=0.014 * P=0.126 P=0.042 * P=0.012 * | |POLY 6 | P=0.012 * P=0.118 P=0.064 P=0.009 ** | |LOGISTIC REGRESSION| P=0.013 * P=0.110 P=0.053 P=0.008 ** | |COCH-ARM / FISHERS | P=0.022 * P=0.130 P=0.033 * P=0.019 * | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 4/48 (8%) 5/48 (10%) | |POLY-3 RATE (b) | 2/41.66 3/38.60 4/44.32 5/38.12 | |POLY-3 PERCENT (g) | 4.8% 7.8% 9.0% 13.1% | |TERMINAL (d) | 0/29 (0%) 1/23 (4%) 2/32 (6%) 2/25 (8%) | |FIRST INCIDENCE | 401 641 508 619 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.140 P=0.458 P=0.378 P=0.188 | |POLY 3 | P=0.131 P=0.465 P=0.366 P=0.180 | |POLY 1.5 | P=0.135 P=0.480 P=0.354 P=0.189 | |POLY 6 | P=0.131 P=0.448 P=0.380 P=0.173 | |LOGISTIC REGRESSION| P=0.193 P=0.525 P=0.094 P=0.277 | |COCH-ARM / FISHERS | P=0.152 P=0.500 P=0.339 P=0.218 | |ORDER RESTRICTED | P=0.148 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/48 (6%) 6/48 (13%) 2/48 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 3/40.06 6/40.64 2/43.66 3/37.18 | |POLY-3 PERCENT (g) | 7.5% 14.8% 4.6% 8.1% | |TERMINAL (d) | 3/29 (10%) 2/23 (9%) 1/32 (3%) 3/25 (12%) | |FIRST INCIDENCE | 728 (T) 485 652 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.354N P=0.188 P=0.442N P=0.594 | |POLY 3 | P=0.353N P=0.247 P=0.461N P=0.628 | |POLY 1.5 | P=0.351N P=0.246 P=0.476N P=0.638 | |POLY 6 | P=0.354N P=0.245 P=0.444N P=0.617 | |LOGISTIC REGRESSION| P=0.328N P=0.258 P=0.452N P=0.594 | |COCH-ARM / FISHERS | P=0.336N P=0.243 P=0.500N P=0.661N | |ORDER RESTRICTED | P=0.356N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 3/48 (6%) 8/48 (17%) | |POLY-3 RATE (b) | 2/40.48 3/38.68 3/43.37 8/38.61 | |POLY-3 PERCENT (g) | 4.9% 7.8% 6.9% 20.7% | |TERMINAL (d) | 1/29 (3%) 2/23 (9%) 3/32 (9%) 5/25 (20%) | |FIRST INCIDENCE | 606 598 728 (T) 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.014 * P=0.419 P=0.546 P=0.033 * | |POLY 3 | P=0.015 * P=0.479 P=0.531 P=0.035 * | |POLY 1.5 | P=0.015 * P=0.489 P=0.520 P=0.038 * | |POLY 6 | P=0.015 * P=0.464 P=0.542 P=0.033 * | |LOGISTIC REGRESSION| P=0.015 * P=0.495 P=0.532 P=0.044 * | |COCH-ARM / FISHERS | P=0.018 * P=0.500 P=0.500 P=0.045 * | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 2/48 (4%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.06 2/38.24 0/43.37 0/37.18 | |POLY-3 PERCENT (g) | 2.5% 5.2% 0.0% 0.0% | |TERMINAL (d) | 1/29 (3%) 2/23 (9%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155N P=0.419 P=0.480N P=0.530N | |POLY 3 | P=0.154N P=0.484 P=0.484N P=0.515N | |POLY 1.5 | P=0.155N P=0.492 P=0.490N P=0.511N | |POLY 6 | P=0.153N P=0.472 P=0.478N P=0.520N | |LOGISTIC REGRESSION| P=0.155N P=0.419 (e) (e) | |COCH-ARM / FISHERS | P=0.155N P=0.500 P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.172N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Inflammation Focal Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/48 (38%) 15/48 (31%) 23/48 (48%) 19/48 (40%) | |POLY-3 RATE (b) | 18/40.40 15/39.44 23/44.82 19/38.83 | |POLY-3 PERCENT (g) | 44.6% 38.0% 51.3% 48.9% | |TERMINAL (d) | 17/29 (59%) 13/23 (57%) 19/32 (59%) 14/25 (56%) | |FIRST INCIDENCE | 631 512 484 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206 P=0.547 P=0.335 P=0.279 | |POLY 3 | P=0.239 P=0.354N P=0.339 P=0.432 | |POLY 1.5 | P=0.237 P=0.341N P=0.280 P=0.444 | |POLY 6 | P=0.255 P=0.384N P=0.411 P=0.426 | |LOGISTIC REGRESSION| P=0.205 P=0.455N P=0.363 P=0.334 | |COCH-ARM / FISHERS | P=0.281 P=0.334N P=0.205 P=0.500 | |ORDER RESTRICTED | P=0.334 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 0/40.06 2/38.32 0/43.37 1/37.29 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 2.7% | |TERMINAL (d) | 0/29 (0%) 1/23 (4%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 708 --- 699 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.576 P=0.200 (e) P=0.459 | |POLY 3 | P=0.583 P=0.227 (e) P=0.486 | |POLY 1.5 | P=0.587 P=0.232 (e) P=0.490 | |POLY 6 | P=0.577 P=0.219 (e) P=0.481 | |LOGISTIC REGRESSION| P=0.590 P=0.212 (e) P=0.484 | |COCH-ARM / FISHERS | P=0.600 P=0.247 (e) P=0.500 | |ORDER RESTRICTED | P=0.311 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 2/48 (4%) 1/48 (2%) | |POLY-3 RATE (b) | 0/40.06 2/38.24 2/43.81 1/37.45 | |POLY-3 PERCENT (g) | 0.0% 5.2% 4.6% 2.7% | |TERMINAL (d) | 0/29 (0%) 2/23 (9%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- 728 (T) 603 654 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.493 P=0.188 P=0.266 P=0.488 | |POLY 3 | P=0.466 P=0.226 P=0.257 P=0.487 | |POLY 1.5 | P=0.474 P=0.232 P=0.249 P=0.490 | |POLY 6 | P=0.459 P=0.218 P=0.266 P=0.483 | |LOGISTIC REGRESSION| P=0.490 P=0.188 P=0.208 P=0.504 | |COCH-ARM / FISHERS | P=0.500 P=0.247 P=0.247 P=0.500 | |ORDER RESTRICTED | P=0.237 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/48 (8%) 4/48 (8%) 1/48 (2%) 6/48 (13%) | |POLY-3 RATE (b) | 4/41.39 4/38.98 1/43.63 6/38.64 | |POLY-3 PERCENT (g) | 9.7% 10.3% 2.3% 15.5% | |TERMINAL (d) | 1/29 (3%) 1/23 (4%) 0/32 (0%) 4/25 (16%) | |FIRST INCIDENCE | 529 613 659 111 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.301 P=0.549 P=0.152N P=0.306 | |POLY 3 | P=0.312 P=0.611 P=0.162N P=0.325 | |POLY 1.5 | P=0.313 P=0.626 P=0.168N P=0.343 | |POLY 6 | P=0.309 P=0.589 P=0.157N P=0.303 | |LOGISTIC REGRESSION| P=0.392 P=0.631N P=0.257N P=0.451 | |COCH-ARM / FISHERS | P=0.319 P=0.643N P=0.181N P=0.370 | |ORDER RESTRICTED | P=0.156 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/48 (21%) 10/48 (21%) 9/48 (19%) 5/48 (10%) | |POLY-3 RATE (b) | 10/40.44 10/38.87 9/44.04 5/37.29 | |POLY-3 PERCENT (g) | 24.7% 25.7% 20.4% 13.4% | |TERMINAL (d) | 8/29 (28%) 8/23 (35%) 7/32 (22%) 4/25 (16%) | |FIRST INCIDENCE | 641 539 603 699 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.097N P=0.394 P=0.398N P=0.211N | |POLY 3 | P=0.101N P=0.562 P=0.417N P=0.163N | |POLY 1.5 | P=0.100N P=0.581 P=0.449N P=0.153N | |POLY 6 | P=0.101N P=0.529 P=0.383N P=0.176N | |LOGISTIC REGRESSION| P=0.095N P=0.508 P=0.396N P=0.185N | |COCH-ARM / FISHERS | P=0.087N P=0.599N P=0.500N P=0.130N | |ORDER RESTRICTED | P=0.160N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/48 (0%) 4/48 (8%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 0/43.37 4/38.99 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 10.3% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- 378 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) P=0.056 | |POLY 3 | P=0.002 ** (e) (e) P=0.056 | |POLY 1.5 | P=0.002 ** (e) (e) P=0.057 | |POLY 6 | P=0.003 ** (e) (e) P=0.055 | |LOGISTIC REGRESSION| P=0.007 ** (e) (e) P=0.088 | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) P=0.059 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lung | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) 4/48 (8%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 1/43.37 4/38.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 10.5% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 2/25 (8%) | |FIRST INCIDENCE | --- --- 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** (e) P=0.520 P=0.054 | |POLY 3 | P=0.004 ** (e) P=0.516 P=0.053 | |POLY 1.5 | P=0.004 ** (e) P=0.510 P=0.055 | |POLY 6 | P=0.004 ** (e) P=0.522 P=0.051 | |LOGISTIC REGRESSION| P=0.005 ** (e) P=0.520 P=0.065 | |COCH-ARM / FISHERS | P=0.005 ** (e) P=0.500 P=0.059 | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 0/43.37 2/38.17 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.2% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | --- --- --- 111 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.042 * (e) (e) P=0.223 | |POLY 3 | P=0.043 * (e) (e) P=0.226 | |POLY 1.5 | P=0.043 * (e) (e) P=0.230 | |POLY 6 | P=0.043 * (e) (e) P=0.221 | |LOGISTIC REGRESSION| P=0.154 (e) (e) P=0.423 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.025 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lung | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 3/48 (6%) 4/48 (8%) 8/48 (17%) | |POLY-3 RATE (b) | 1/40.06 3/38.79 4/43.37 8/38.16 | |POLY-3 PERCENT (g) | 2.5% 7.7% 9.2% 21.0% | |TERMINAL (d) | 1/29 (3%) 2/23 (9%) 4/32 (13%) 6/25 (24%) | |FIRST INCIDENCE | 728 (T) 556 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005 ** P=0.248 P=0.208 P=0.011 * | |POLY 3 | P=0.005 ** P=0.293 P=0.203 P=0.011 * | |POLY 1.5 | P=0.006 ** P=0.299 P=0.194 P=0.013 * | |POLY 6 | P=0.005 ** P=0.283 P=0.213 P=0.010 * | |LOGISTIC REGRESSION| P=0.005 ** P=0.295 P=0.208 P=0.013 * | |COCH-ARM / FISHERS | P=0.007 ** P=0.308 P=0.181 P=0.015 * | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 1/48 (2%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.06 1/38.40 2/43.37 0/37.18 | |POLY-3 PERCENT (g) | 2.5% 2.6% 4.6% 0.0% | |TERMINAL (d) | 1/29 (3%) 0/23 (0%) 2/32 (6%) 0/25 (0%) | |FIRST INCIDENCE | 728 (T) 686 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.382N P=0.727 P=0.535 P=0.530N | |POLY 3 | P=0.390N P=0.752 P=0.528 P=0.515N | |POLY 1.5 | P=0.386N P=0.756 P=0.517 P=0.511N | |POLY 6 | P=0.393N P=0.745 P=0.539 P=0.520N | |LOGISTIC REGRESSION| P=0.382N P=0.746 P=0.535 (e) | |COCH-ARM / FISHERS | P=0.370N P=0.753N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.292N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 0/46 (0%) 2/47 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/39.12 0/37.27 2/42.58 0/37.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.7% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/31 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 673 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.554 (e) P=0.266 (e) | |POLY 3 | P=0.520 (e) P=0.256 (e) | |POLY 1.5 | P=0.534 (e) P=0.249 (e) | |POLY 6 | P=0.504 (e) P=0.264 (e) | |LOGISTIC REGRESSION| P=0.559 (e) P=0.249 (e) | |COCH-ARM / FISHERS | P=0.568 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.265 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/47 (2%) 3/46 (7%) 2/47 (4%) 5/48 (10%) | |POLY-3 RATE (b) | 1/39.12 3/37.48 2/42.37 5/39.70 | |POLY-3 PERCENT (g) | 2.6% 8.0% 4.7% 12.6% | |TERMINAL (d) | 1/29 (3%) 1/23 (4%) 2/31 (7%) 1/25 (4%) | |FIRST INCIDENCE | 728 (T) 687 728 (T) 111 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.081 P=0.248 P=0.523 P=0.095 | |POLY 3 | P=0.096 P=0.289 P=0.528 P=0.103 | |POLY 1.5 | P=0.095 P=0.293 P=0.517 P=0.103 | |POLY 6 | P=0.098 P=0.282 P=0.538 P=0.103 | |LOGISTIC REGRESSION| P=0.138 P=0.273 P=0.523 P=0.180 | |COCH-ARM / FISHERS | P=0.095 P=0.300 P=0.500 P=0.107 | |ORDER RESTRICTED | P=0.058 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/47 (11%) 5/46 (11%) 5/47 (11%) 7/48 (15%) | |POLY-3 RATE (b) | 5/39.82 5/37.59 5/42.67 7/39.17 | |POLY-3 PERCENT (g) | 12.6% 13.3% 11.7% 17.9% | |TERMINAL (d) | 2/29 (7%) 4/23 (17%) 2/31 (7%) 3/25 (12%) | |FIRST INCIDENCE | 631 641 692 323 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.267 P=0.501 P=0.565N P=0.308 | |POLY 3 | P=0.305 P=0.595 P=0.587N P=0.365 | |POLY 1.5 | P=0.304 P=0.606 P=0.603N P=0.372 | |POLY 6 | P=0.307 P=0.576 P=0.572N P=0.356 | |LOGISTIC REGRESSION| P=0.302 P=0.597 P=0.592N P=0.408 | |COCH-ARM / FISHERS | P=0.314 P=0.616 P=0.630N P=0.395 | |ORDER RESTRICTED | P=0.390 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/47 (4%) 0/47 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/39.37 0/38.01 0/43.37 0/37.18 | |POLY-3 PERCENT (g) | 5.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/28 (4%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 641 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138N P=0.275N P=0.209N P=0.269N | |POLY 3 | P=0.124N P=0.244N P=0.216N P=0.250N | |POLY 1.5 | P=0.129N P=0.240N P=0.222N P=0.245N | |POLY 6 | P=0.117N P=0.252N P=0.210N P=0.256N | |LOGISTIC REGRESSION| P=0.136N P=0.240N P=0.232N P=0.243N | |COCH-ARM / FISHERS | P=0.136N P=0.247N P=0.242N P=0.242N | |ORDER RESTRICTED | P=0.034N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/7 (0%) 0/7 (0%) 2/5 (40%) | |POLY-3 RATE (b) | 0/8.22 0/5.22 0/6.13 2/4.15 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 48.2% | |TERMINAL (d) | 0/4 (0%) 0/2 (0%) 0/4 (0%) 1/2 (50%) | |FIRST INCIDENCE | --- --- --- 694 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.027 * (e) (e) P=0.150 | |POLY 3 | P=0.005 ** (e) (e) P=0.060 | |POLY 1.5 | P=0.005 ** (e) (e) P=0.062 | |POLY 6 | P=0.005 ** (e) (e) P=0.058 | |LOGISTIC REGRESSION| P=0.012 * (e) (e) P=0.075 | |COCH-ARM / FISHERS | P=0.013 * (e) (e) P=0.095 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/7 (0%) 0/7 (0%) 1/5 (20%) | |POLY-3 RATE (b) | 2/8.29 0/5.22 0/6.13 1/4.01 | |POLY-3 PERCENT (g) | 24.1% 0.0% 0.0% 24.9% | |TERMINAL (d) | 1/4 (25%) 0/2 (0%) 0/4 (0%) 1/2 (50%) | |FIRST INCIDENCE | 711 --- --- 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.585N P=0.336N P=0.230N P=0.691N | |POLY 3 | P=0.636N P=0.336N P=0.294N P=0.739 | |POLY 1.5 | P=0.647N P=0.328N P=0.302N P=0.739 | |POLY 6 | P=0.621N P=0.345N P=0.283N P=0.737 | |LOGISTIC REGRESSION| P=0.674N P=0.340N P=0.265N P=0.739 | |COCH-ARM / FISHERS | P=0.665N P=0.331N P=0.331N P=0.736 | |ORDER RESTRICTED | P=0.342N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 1/7 (14%) 3/7 (43%) 0/5 (0%) | |POLY-3 RATE (b) | 1/8.22 1/5.60 3/6.56 0/4.01 | |POLY-3 PERCENT (g) | 12.2% 17.9% 45.7% 0.0% | |TERMINAL (d) | 1/4 (25%) 0/2 (0%) 2/4 (50%) 0/2 (0%) | |FIRST INCIDENCE | 728 (T) 624 603 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.505N P=0.665 P=0.300 P=0.638N | |POLY 3 | P=0.614 P=0.677 P=0.190 P=0.642N | |POLY 1.5 | P=0.626 P=0.675 P=0.174 P=0.639N | |POLY 6 | P=0.592 P=0.686 P=0.216 P=0.646N | |LOGISTIC REGRESSION| P=0.629N P=0.679 P=0.176 (e) | |COCH-ARM / FISHERS | P=0.634N P=0.669 P=0.162 P=0.667N | |ORDER RESTRICTED | P=0.292N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/7 (0%) 0/7 (0%) 0/5 (0%) | |POLY-3 RATE (b) | 2/8.64 0/5.22 0/6.13 0/4.01 | |POLY-3 PERCENT (g) | 23.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/4 (25%) 0/2 (0%) 0/4 (0%) 0/2 (0%) | |FIRST INCIDENCE | 606 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.153N P=0.339N P=0.227N P=0.327N | |POLY 3 | P=0.174N P=0.349N P=0.306N P=0.415N | |POLY 1.5 | P=0.183N P=0.334N P=0.308N P=0.407N | |POLY 6 | P=0.162N P=0.365N P=0.303N P=0.430N | |LOGISTIC REGRESSION| P=0.198N P=0.311N P=0.327N P=0.391N | |COCH-ARM / FISHERS | P=0.197N P=0.331N P=0.331N P=0.429N | |ORDER RESTRICTED | P=0.158N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/7 (0%) 1/7 (14%) 0/5 (0%) | |POLY-3 RATE (b) | 2/8.24 0/5.22 1/6.13 0/4.01 | |POLY-3 PERCENT (g) | 24.3% 0.0% 16.3% 0.0% | |TERMINAL (d) | 1/4 (25%) 0/2 (0%) 1/4 (25%) 0/2 (0%) | |FIRST INCIDENCE | 722 --- 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.265N P=0.348N P=0.492N P=0.337N | |POLY 3 | P=0.319N P=0.335N P=0.610N P=0.402N | |POLY 1.5 | P=0.327N P=0.327N P=0.617N P=0.399N | |POLY 6 | P=0.311N P=0.341N P=0.598N P=0.406N | |LOGISTIC REGRESSION| P=0.319N P=0.353N P=0.555N P=0.434N | |COCH-ARM / FISHERS | P=0.335N P=0.331N P=0.640N P=0.429N | |ORDER RESTRICTED | P=0.224N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Galactocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/46 (9%) 8/48 (17%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 4/38.49 8/39.99 2/43.65 2/37.52 | |POLY-3 PERCENT (g) | 10.4% 20.0% 4.6% 5.3% | |TERMINAL (d) | 2/27 (7%) 4/23 (17%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | 626 485 666 633 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.085N P=0.130 P=0.282N P=0.392N | |POLY 3 | P=0.073N P=0.191 P=0.280N P=0.348N | |POLY 1.5 | P=0.073N P=0.196 P=0.295N P=0.340N | |POLY 6 | P=0.072N P=0.181 P=0.266N P=0.357N | |LOGISTIC REGRESSION| P=0.070N P=0.197 P=0.294N P=0.344N | |COCH-ARM / FISHERS | P=0.070N P=0.199 P=0.318N P=0.318N | |ORDER RESTRICTED | P=0.104N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 28/46 (61%) 33/48 (69%) 29/48 (60%) 35/48 (73%) | |POLY-3 RATE (b) | 28/42.54 33/43.96 29/46.60 35/42.66 | |POLY-3 PERCENT (g) | 65.8% 75.1% 62.2% 82.1% | |TERMINAL (d) | 15/27 (56%) 16/23 (70%) 16/32 (50%) 19/25 (76%) | |FIRST INCIDENCE | 526 443 603 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201 P=0.110 P=0.352N P=0.084 | |POLY 3 | P=0.122 P=0.232 P=0.448N P=0.064 | |POLY 1.5 | P=0.127 P=0.257 P=0.491N P=0.076 | |POLY 6 | P=0.132 P=0.193 P=0.410N P=0.061 | |LOGISTIC REGRESSION| P=0.146 P=0.254 P=0.533N P=0.082 | |COCH-ARM / FISHERS | P=0.198 P=0.280 P=0.566N P=0.153 | |ORDER RESTRICTED | P=0.067 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Mammary Gland: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/46 (26%) 22/48 (46%) 18/48 (38%) 11/48 (23%) | |POLY-3 RATE (b) | 12/40.03 22/41.36 18/45.47 11/38.63 | |POLY-3 PERCENT (g) | 30.0% 53.2% 39.6% 28.5% | |TERMINAL (d) | 6/27 (22%) 12/23 (52%) 9/32 (28%) 5/25 (20%) | |FIRST INCIDENCE | 443 485 619 589 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.212N P=0.016 * P=0.300 P=0.572 | |POLY 3 | P=0.195N P=0.024 * P=0.241 P=0.541N | |POLY 1.5 | P=0.186N P=0.029 * P=0.208 P=0.517N | |POLY 6 | P=0.196N P=0.019 * P=0.287 P=0.561N | |LOGISTIC REGRESSION| P=0.166N P=0.032 * P=0.170 P=0.503N | |COCH-ARM / FISHERS | P=0.146N P=0.037 * P=0.167 P=0.453N | |ORDER RESTRICTED | P=0.172N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/9 (78%) 4/5 (80%) 2/2 (100%) 3/4 (75%) | |POLY-3 RATE (b) | 7/8.03 4/4.60 2/2.00 3/3.53 | |POLY-3 PERCENT (g) | 87.2% 87.0% 100.0% 85.0% | |TERMINAL (d) | 6/6 (100%) 1/1 (100%) 0/0 (0%) 2/2 (100%) | |FIRST INCIDENCE | 704 512 484 630 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.456N P=0.276 P=0.520 P=0.733 | |POLY 3 | P=0.692 P=0.846N P=0.831 P=0.839N | |POLY 1.5 | P=0.659 P=0.780 P=0.714 P=0.769N | |POLY 6 | P=0.778 P=0.945N P=0.981 P=0.961N | |LOGISTIC REGRESSION| P=0.605 P=0.363 P=0.231 (e) | |COCH-ARM / FISHERS | P=0.642 P=0.769N P=0.655 P=0.706N | |ORDER RESTRICTED | P=0.639N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 1/43.37 2/38.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 5.2% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059 (e) P=0.520 P=0.228 | |POLY 3 | P=0.061 (e) P=0.516 P=0.226 | |POLY 1.5 | P=0.061 (e) P=0.510 P=0.228 | |POLY 6 | P=0.061 (e) P=0.522 P=0.223 | |LOGISTIC REGRESSION| P=0.084 (e) P=0.520 P=0.294 | |COCH-ARM / FISHERS | P=0.064 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.067 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 1/43.37 2/38.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 5.2% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059 (e) P=0.520 P=0.228 | |POLY 3 | P=0.061 (e) P=0.516 P=0.226 | |POLY 1.5 | P=0.061 (e) P=0.510 P=0.228 | |POLY 6 | P=0.061 (e) P=0.522 P=0.223 | |LOGISTIC REGRESSION| P=0.084 (e) P=0.520 P=0.294 | |COCH-ARM / FISHERS | P=0.064 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.067 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/48 (40%) 10/48 (21%) 11/48 (23%) 13/48 (27%) | |POLY-3 RATE (b) | 19/42.93 10/39.71 11/43.63 13/39.70 | |POLY-3 PERCENT (g) | 44.3% 25.2% 25.2% 32.7% | |TERMINAL (d) | 10/29 (35%) 6/23 (26%) 10/32 (31%) 6/25 (24%) | |FIRST INCIDENCE | 535 485 659 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.291N P=0.134N P=0.039N* P=0.285N | |POLY 3 | P=0.251N P=0.052N P=0.047N* P=0.195N | |POLY 1.5 | P=0.256N P=0.042N* P=0.050N P=0.178N | |POLY 6 | P=0.243N P=0.073N P=0.049N* P=0.218N | |LOGISTIC REGRESSION| P=0.269N P=0.043N* P=0.043N* P=0.169N | |COCH-ARM / FISHERS | P=0.241N P=0.037N* P=0.061N P=0.139N | |ORDER RESTRICTED | P=0.075N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 3/48 (6%) 6/48 (13%) 1/48 (2%) | |POLY-3 RATE (b) | 2/40.06 3/38.24 6/43.37 1/37.18 | |POLY-3 PERCENT (g) | 5.0% 7.9% 13.8% 2.7% | |TERMINAL (d) | 2/29 (7%) 3/23 (13%) 6/32 (19%) 1/25 (4%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.440N P=0.393 P=0.163 P=0.552N | |POLY 3 | P=0.466N P=0.479 P=0.159 P=0.526N | |POLY 1.5 | P=0.456N P=0.489 P=0.149 P=0.519N | |POLY 6 | P=0.475N P=0.463 P=0.169 P=0.535N | |LOGISTIC REGRESSION| P=0.440N P=0.393 P=0.163 P=0.552N | |COCH-ARM / FISHERS | P=0.423N P=0.500 P=0.134 P=0.500N | |ORDER RESTRICTED | P=0.235N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium, Respiratory Epithelium | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 0/48 (0%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.06 0/38.24 2/43.37 0/37.18 | |POLY-3 PERCENT (g) | 2.5% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/29 (3%) 0/23 (0%) 2/32 (6%) 0/25 (0%) | |FIRST INCIDENCE | 728 (T) --- 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.510N P=0.546N P=0.535 P=0.530N | |POLY 3 | P=0.515N P=0.509N P=0.528 P=0.515N | |POLY 1.5 | P=0.513N P=0.505N P=0.517 P=0.511N | |POLY 6 | P=0.516N P=0.516N P=0.539 P=0.520N | |LOGISTIC REGRESSION| P=0.510N (e) P=0.535 (e) | |COCH-ARM / FISHERS | P=0.500N P=0.500N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.339N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/48 (38%) 14/48 (29%) 11/47 (23%) 10/48 (21%) | |POLY-3 RATE (b) | 18/42.33 14/41.35 11/43.73 10/37.74 | |POLY-3 PERCENT (g) | 42.5% 33.9% 25.2% 26.5% | |TERMINAL (d) | 10/29 (35%) 6/23 (26%) 6/32 (19%) 8/25 (32%) | |FIRST INCIDENCE | 533 539 627 634 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.069N P=0.474N P=0.063N P=0.141N | |POLY 3 | P=0.067N P=0.275N P=0.067N P=0.098N | |POLY 1.5 | P=0.061N P=0.265N P=0.078N P=0.081N | |POLY 6 | P=0.076N P=0.296N P=0.058N P=0.128N | |LOGISTIC REGRESSION| P=0.054N P=0.272N P=0.081N P=0.086N | |COCH-ARM / FISHERS | P=0.047N* P=0.258N P=0.102N P=0.058N | |ORDER RESTRICTED | P=0.083N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 4/48 (8%) 7/47 (15%) 11/48 (23%) | |POLY-3 RATE (b) | 5/40.75 4/38.65 7/43.60 11/38.56 | |POLY-3 PERCENT (g) | 12.3% 10.4% 16.1% 28.5% | |TERMINAL (d) | 2/29 (7%) 3/23 (13%) 5/32 (16%) 8/25 (32%) | |FIRST INCIDENCE | 626 610 484 508 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.018 * P=0.614N P=0.455 P=0.053 | |POLY 3 | P=0.019 * P=0.533N P=0.427 P=0.061 | |POLY 1.5 | P=0.019 * P=0.517N P=0.403 P=0.067 | |POLY 6 | P=0.019 * P=0.560N P=0.450 P=0.054 | |LOGISTIC REGRESSION| P=0.018 * P=0.528N P=0.356 P=0.065 | |COCH-ARM / FISHERS | P=0.023 * P=0.500N P=0.364 P=0.085 | |ORDER RESTRICTED | P=0.027 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 1/43.37 2/37.70 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 5.3% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 1/25 (4%) | |FIRST INCIDENCE | --- --- 728 (T) 570 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059 (e) P=0.520 P=0.221 | |POLY 3 | P=0.060 (e) P=0.516 P=0.223 | |POLY 1.5 | P=0.060 (e) P=0.510 P=0.227 | |POLY 6 | P=0.060 (e) P=0.522 P=0.220 | |LOGISTIC REGRESSION| P=0.062 (e) P=0.520 P=0.242 | |COCH-ARM / FISHERS | P=0.064 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.066 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/48 (27%) 14/48 (29%) 12/48 (25%) 7/48 (15%) | |POLY-3 RATE (b) | 13/42.71 14/40.14 12/44.51 7/38.16 | |POLY-3 PERCENT (g) | 30.4% 34.9% 27.0% 18.3% | |TERMINAL (d) | 6/29 (21%) 7/23 (30%) 8/32 (25%) 4/25 (16%) | |FIRST INCIDENCE | 529 577 508 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.080N P=0.330 P=0.388N P=0.187N | |POLY 3 | P=0.081N P=0.422 P=0.451N P=0.157N | |POLY 1.5 | P=0.074N P=0.458 P=0.467N P=0.137N | |POLY 6 | P=0.092N P=0.373 P=0.443N P=0.185N | |LOGISTIC REGRESSION| P=0.063N P=0.484 P=0.530N P=0.116N | |COCH-ARM / FISHERS | P=0.056N P=0.500 P=0.500N P=0.104N | |ORDER RESTRICTED | P=0.118N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 2/47 (4%) 2/46 (4%) 2/45 (4%) | |POLY-3 RATE (b) | 5/40.75 2/38.76 2/42.41 2/35.73 | |POLY-3 PERCENT (g) | 12.3% 5.2% 4.7% 5.6% | |TERMINAL (d) | 3/29 (10%) 0/23 (0%) 1/32 (3%) 2/25 (8%) | |FIRST INCIDENCE | 535 540 673 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.225N P=0.275N P=0.184N P=0.280N | |POLY 3 | P=0.232N P=0.235N P=0.199N P=0.271N | |POLY 1.5 | P=0.235N P=0.229N P=0.212N P=0.264N | |POLY 6 | P=0.226N P=0.246N P=0.186N P=0.280N | |LOGISTIC REGRESSION| P=0.233N P=0.222N P=0.230N P=0.262N | |COCH-ARM / FISHERS | P=0.231N P=0.226N P=0.235N P=0.245N | |ORDER RESTRICTED | P=0.178N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/48 (17%) 5/47 (11%) 9/46 (20%) 9/45 (20%) | |POLY-3 RATE (b) | 8/41.50 5/38.72 9/42.92 9/38.48 | |POLY-3 PERCENT (g) | 19.3% 12.9% 21.0% 23.4% | |TERMINAL (d) | 5/29 (17%) 2/23 (9%) 7/32 (22%) 3/25 (12%) | |FIRST INCIDENCE | 443 591 508 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.245 P=0.394N P=0.583 P=0.397 | |POLY 3 | P=0.241 P=0.319N P=0.531 P=0.431 | |POLY 1.5 | P=0.227 P=0.305N P=0.505 P=0.425 | |POLY 6 | P=0.263 P=0.342N P=0.555 P=0.440 | |LOGISTIC REGRESSION| P=0.235 P=0.291N P=0.442 P=0.471 | |COCH-ARM / FISHERS | P=0.227 P=0.290N P=0.461 P=0.441 | |ORDER RESTRICTED | P=0.330 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/48 (10%) 0/47 (0%) 11/46 (24%) 6/45 (13%) | |POLY-3 RATE (b) | 5/40.37 0/38.01 11/43.23 6/37.98 | |POLY-3 PERCENT (g) | 12.4% 0.0% 25.5% 15.8% | |TERMINAL (d) | 4/29 (14%) 0/23 (0%) 9/32 (28%) 2/25 (8%) | |FIRST INCIDENCE | 641 --- 508 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.094 P=0.054N P=0.125 P=0.417 | |POLY 3 | P=0.089 P=0.035N* P=0.106 P=0.457 | |POLY 1.5 | P=0.080 P=0.033N* P=0.091 P=0.449 | |POLY 6 | P=0.105 P=0.038N* P=0.123 P=0.466 | |LOGISTIC REGRESSION| P=0.086 P=0.040N* P=0.092 P=0.472 | |COCH-ARM / FISHERS | P=0.087 P=0.030N* P=0.071 P=0.454 | |ORDER RESTRICTED | P=0.040 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/47 (4%) 1/48 (2%) 1/48 (2%) | |POLY-3 RATE (b) | 0/40.06 2/38.29 1/43.37 1/37.65 | |POLY-3 PERCENT (g) | 0.0% 5.2% 2.3% 2.7% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- 648 728 (T) 589 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.534 P=0.226 P=0.520 P=0.485 | |POLY 3 | P=0.522 P=0.227 P=0.516 P=0.488 | |POLY 1.5 | P=0.528 P=0.229 P=0.510 P=0.491 | |POLY 6 | P=0.517 P=0.222 P=0.522 P=0.484 | |LOGISTIC REGRESSION| P=0.555 P=0.234 P=0.520 P=0.543 | |COCH-ARM / FISHERS | P=0.547 P=0.242 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.280 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Skin | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/40.42 0/38.24 0/43.37 0/37.18 | |POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 647 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.139N P=0.270N P=0.207N P=0.274N | |POLY 3 | P=0.124N P=0.249N P=0.221N P=0.256N | |POLY 1.5 | P=0.130N P=0.243N P=0.227N P=0.250N | |POLY 6 | P=0.116N P=0.259N P=0.216N P=0.263N | |LOGISTIC REGRESSION| P=0.139N P=0.240N P=0.243N P=0.245N | |COCH-ARM / FISHERS | P=0.139N P=0.247N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Skin: Epidermis | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/40.06 2/38.32 0/43.37 0/37.18 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 0.0% | |TERMINAL (d) | 0/29 (0%) 1/23 (4%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 708 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.333N P=0.200 (e) (e) | |POLY 3 | P=0.324N P=0.227 (e) (e) | |POLY 1.5 | P=0.323N P=0.232 (e) (e) | |POLY 6 | P=0.327N P=0.219 (e) (e) | |LOGISTIC REGRESSION| P=0.326N P=0.212 (e) (e) | |COCH-ARM / FISHERS | P=0.321N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.253N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/48 (13%) 2/48 (4%) 7/48 (15%) 12/48 (25%) | |POLY-3 RATE (b) | 6/43.71 2/38.24 7/44.56 12/42.42 | |POLY-3 PERCENT (g) | 13.7% 5.2% 15.7% 28.3% | |TERMINAL (d) | 0/29 (0%) 2/23 (9%) 4/32 (13%) 1/25 (4%) | |FIRST INCIDENCE | 401 728 (T) 484 323 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * P=0.171N P=0.557 P=0.089 | |POLY 3 | P=0.010 * P=0.179N P=0.515 P=0.079 | |POLY 1.5 | P=0.009 ** P=0.158N P=0.509 P=0.082 | |POLY 6 | P=0.013 * P=0.209N P=0.520 P=0.079 | |LOGISTIC REGRESSION| P=0.023 * P=0.095N P=0.170 P=0.195 | |COCH-ARM / FISHERS | P=0.009 ** P=0.134N P=0.500 P=0.095 | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 2/48 (4%) 2/48 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 1/40.42 2/39.54 2/43.78 3/39.36 | |POLY-3 PERCENT (g) | 2.5% 5.1% 4.6% 7.6% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 626 485 652 111 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.229 P=0.485 P=0.555 P=0.286 | |POLY 3 | P=0.236 P=0.492 P=0.528 P=0.295 | |POLY 1.5 | P=0.237 P=0.497 P=0.517 P=0.299 | |POLY 6 | P=0.235 P=0.484 P=0.539 P=0.290 | |LOGISTIC REGRESSION| P=0.507 P=0.504 P=0.448 P=0.573 | |COCH-ARM / FISHERS | P=0.239 P=0.500 P=0.500 P=0.308 | |ORDER RESTRICTED | P=0.234 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 2/48 (4%) 1/48 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.37 2/39.39 1/43.63 0/37.18 | |POLY-3 PERCENT (g) | 2.5% 5.1% 2.3% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 641 485 659 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.226N P=0.480 P=0.719N P=0.530N | |POLY 3 | P=0.232N P=0.491 P=0.743N P=0.516N | |POLY 1.5 | P=0.230N P=0.496 P=0.750N P=0.511N | |POLY 6 | P=0.235N P=0.483 P=0.736N P=0.523N | |LOGISTIC REGRESSION| P=0.155N P=0.513 P=0.727 P=0.489N | |COCH-ARM / FISHERS | P=0.220N P=0.500 P=0.753N P=0.500N | |ORDER RESTRICTED | P=0.237N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/46 (17%) 5/48 (10%) 11/47 (23%) 6/46 (13%) | |POLY-3 RATE (b) | 8/39.19 5/38.76 11/43.50 6/35.84 | |POLY-3 PERCENT (g) | 20.4% 12.9% 25.3% 16.7% | |TERMINAL (d) | 5/29 (17%) 3/23 (13%) 7/31 (23%) 4/24 (17%) | |FIRST INCIDENCE | 589 598 619 654 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.528 P=0.411N P=0.392 P=0.513N | |POLY 3 | P=0.515 P=0.278N P=0.396 P=0.456N | |POLY 1.5 | P=0.526 P=0.263N P=0.367 P=0.434N | |POLY 6 | P=0.507 P=0.306N P=0.426 P=0.483N | |LOGISTIC REGRESSION| P=0.531 P=0.280N P=0.367 P=0.459N | |COCH-ARM / FISHERS | P=0.531N P=0.249N P=0.323 P=0.386N | |ORDER RESTRICTED | P=0.479 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 1/48 (2%) 1/47 (2%) 3/46 (7%) | |POLY-3 RATE (b) | 0/38.38 1/38.24 1/42.37 3/35.73 | |POLY-3 PERCENT (g) | 0.0% 2.6% 2.4% 8.4% | |TERMINAL (d) | 0/29 (0%) 1/23 (4%) 1/31 (3%) 2/24 (8%) | |FIRST INCIDENCE | --- 728 (T) 728 (T) 619 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.047 * P=0.454 P=0.513 P=0.097 | |POLY 3 | P=0.049 * P=0.499 P=0.520 P=0.105 | |POLY 1.5 | P=0.050 P=0.504 P=0.514 P=0.109 | |POLY 6 | P=0.049 * P=0.492 P=0.525 P=0.101 | |LOGISTIC REGRESSION| P=0.045 * P=0.454 P=0.513 P=0.107 | |COCH-ARM / FISHERS | P=0.054 P=0.511 P=0.505 P=0.121 | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 0/48 (0%) 1/47 (2%) 2/46 (4%) | |POLY-3 RATE (b) | 0/38.38 0/38.24 1/42.37 2/35.34 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 5.7% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/31 (3%) 2/24 (8%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.053 (e) P=0.513 P=0.197 | |POLY 3 | P=0.055 (e) P=0.520 P=0.218 | |POLY 1.5 | P=0.057 (e) P=0.514 P=0.224 | |POLY 6 | P=0.054 (e) P=0.525 P=0.212 | |LOGISTIC REGRESSION| (e) (e) P=0.513 P=0.197 | |COCH-ARM / FISHERS | P=0.061 (e) P=0.505 P=0.247 | |ORDER RESTRICTED | P=0.063 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Trachea | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 3/48 (6%) 1/48 (2%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 3/43.37 1/37.94 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.9% 2.6% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 3/32 (9%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.207 (e) P=0.138 P=0.491 | |POLY 3 | P=0.197 (e) P=0.133 P=0.489 | |POLY 1.5 | P=0.201 (e) P=0.127 P=0.492 | |POLY 6 | P=0.193 (e) P=0.139 P=0.486 | |LOGISTIC REGRESSION| P=0.229 (e) P=0.138 P=0.654 | |COCH-ARM / FISHERS | P=0.220 (e) P=0.121 P=0.500 | |ORDER RESTRICTED | P=0.130 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Trachea: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 1/43.37 2/38.16 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 5.2% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 1/32 (3%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 728 (T) 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059 (e) P=0.520 P=0.228 | |POLY 3 | P=0.061 (e) P=0.516 P=0.226 | |POLY 1.5 | P=0.061 (e) P=0.510 P=0.228 | |POLY 6 | P=0.061 (e) P=0.522 P=0.223 | |LOGISTIC REGRESSION| P=0.084 (e) P=0.520 P=0.294 | |COCH-ARM / FISHERS | P=0.064 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.067 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/48 (13%) 3/48 (6%) 11/48 (23%) 8/48 (17%) | |POLY-3 RATE (b) | 6/41.17 3/38.24 11/43.55 8/37.40 | |POLY-3 PERCENT (g) | 14.6% 7.9% 25.3% 21.4% | |TERMINAL (d) | 3/29 (10%) 3/23 (13%) 9/32 (28%) 7/25 (28%) | |FIRST INCIDENCE | 589 728 (T) 697 670 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.108 P=0.343N P=0.213 P=0.292 | |POLY 3 | P=0.097 P=0.278N P=0.168 P=0.311 | |POLY 1.5 | P=0.105 P=0.260N P=0.159 P=0.335 | |POLY 6 | P=0.089 P=0.307N P=0.175 P=0.280 | |LOGISTIC REGRESSION| P=0.101 P=0.261N P=0.186 P=0.322 | |COCH-ARM / FISHERS | P=0.132 P=0.243N P=0.142 P=0.387 | |ORDER RESTRICTED | P=0.120 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93005 TEST: 03 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - MALACHITE GREEN Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Vagina | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/48 (6%) 3/48 (6%) 5/48 (10%) 1/48 (2%) | |POLY-3 RATE (b) | 3/41.04 3/39.04 5/44.19 1/37.76 | |POLY-3 PERCENT (g) | 7.3% 7.7% 11.3% 2.7% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 0/25 (0%) | |FIRST INCIDENCE | 626 556 659 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.301N P=0.614 P=0.449 P=0.342N | |POLY 3 | P=0.312N P=0.640 P=0.397 P=0.335N | |POLY 1.5 | P=0.304N P=0.651 P=0.382 P=0.326N | |POLY 6 | P=0.322N P=0.622 P=0.414 P=0.348N | |LOGISTIC REGRESSION| P=0.255N P=0.649N P=0.299 P=0.255N | |COCH-ARM / FISHERS | P=0.279N P=0.661N P=0.357 P=0.308N | |ORDER RESTRICTED | P=0.239N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 100 PPM 300 PPM 600 PPM | | | | |=================================================================================================================================| | | |Vagina | | Prolapse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.06 0/38.24 0/43.37 2/37.45 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.3% | |TERMINAL (d) | 0/29 (0%) 0/23 (0%) 0/32 (0%) 1/25 (4%) | |FIRST INCIDENCE | --- --- --- 654 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040 * (e) (e) P=0.217 | |POLY 3 | P=0.042 * (e) (e) P=0.222 | |POLY 1.5 | P=0.042 * (e) (e) P=0.226 | |POLY 6 | P=0.043 * (e) (e) P=0.218 | |LOGISTIC REGRESSION| P=0.040 * (e) (e) P=0.223 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.024 * (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).