TDMS Study 96007-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:15:50 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/CONTROL VS. GRPS. 6,7 & 8 REASONS FOR REMOVAL: 25022 Accidently Killed 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 006 300 NG/KG INCLUDE 007 550 NG/KG INCLUDE 008 1000 NG/KG NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:15:50 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 Rats(SPRAGUE-DAWLEY) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Brain Heart Islets, Pancreatic Kidney Liver Lung Ovary Pancreas Parathyroid Gland Pituitary Gland Salivary Glands Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:15:50 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION ( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Adenoma Adrenal Medulla Pheochromocytoma Benign Pheochromocytoma: Benign, Complex, Malignant, NOS Brain Oligodendroglioma, Glioma, or Astrocytoma Liver Cholangiocarcinoma Hepatocellular Adenoma Hepatocholangioma Lung Cystic Keratinizing Epithelioma Squamous Cell Carcinoma Mammary Gland Carcinoma Carcinoma or Adenoma Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) Squamous Cell Carcinoma Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma Oral Mucosa Squamous Cell Carcinoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Carcinoma or Adenoma Thyroid Gland: C-Cell Adenoma All Organs Hemangiosarcoma Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 1 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 0/36.61 1/41.55 2/32.75 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 6.1% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 722 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.046 * (e) P=0.602 P=0.276 | |POLY 3 | P=0.067 (e) P=0.555 P=0.245 | |POLY 1.5 | P=0.069 (e) P=0.536 P=0.247 | |POLY 6 | P=0.061 (e) P=0.576 P=0.233 | |LOGISTIC REGRESSION| P=0.066 (e) P=0.609 P=0.243 | |COCH-ARM / FISHERS | P=0.070 (e) P=0.500 P=0.252 | |ORDER RESTRICTED | P=0.079 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/53 (2%) 0/52 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 1/37.02 0/41.53 2/32.51 | |POLY-3 PERCENT (g) | 0.0% 2.7% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 607 --- 588 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.124 P=0.561 (e) P=0.229 | |POLY 3 | P=0.149 P=0.533 (e) P=0.243 | |POLY 1.5 | P=0.147 P=0.522 (e) P=0.246 | |POLY 6 | P=0.150 P=0.545 (e) P=0.229 | |LOGISTIC REGRESSION| P=0.137 P=0.508 (e) P=0.241 | |COCH-ARM / FISHERS | P=0.140 P=0.505 (e) P=0.252 | |ORDER RESTRICTED | P=0.078 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 2 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 2/53 (4%) 4/52 (8%) 0/53 (0%) | |POLY-3 RATE (b) | 8/33.26 2/36.68 4/42.10 0/31.91 | |POLY-3 PERCENT (g) | 24.1% 5.5% 9.5% 0.0% | |TERMINAL (d) | 3/15 (20%) 1/16 (6%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | 531 709 618 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005N** P=0.031N* P=0.047N* P=0.018N* | |POLY 3 | P=0.004N** P=0.027N* P=0.081N P=0.003N** | |POLY 1.5 | P=0.004N** P=0.032N* P=0.107N P=0.003N** | |POLY 6 | P=0.004N** P=0.024N* P=0.059N P=0.005N** | |LOGISTIC REGRESSION| P=0.003N** P=0.026N* P=0.087N P=0.004N** | |COCH-ARM / FISHERS | P=0.004N** P=0.043N* P=0.179N P=0.003N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 3/53 (6%) 5/52 (10%) 0/53 (0%) | |POLY-3 RATE (b) | 8/33.26 3/36.68 5/42.10 0/31.91 | |POLY-3 PERCENT (g) | 24.1% 8.2% 11.9% 0.0% | |TERMINAL (d) | 3/15 (20%) 2/16 (13%) 3/23 (13%) 0/7 (0%) | |FIRST INCIDENCE | 531 709 618 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008N** P=0.067N P=0.081N P=0.018N* | |POLY 3 | P=0.005N** P=0.064N P=0.140N P=0.003N** | |POLY 1.5 | P=0.005N** P=0.073N P=0.179N P=0.003N** | |POLY 6 | P=0.007N** P=0.060N P=0.107N P=0.005N** | |LOGISTIC REGRESSION| P=0.004N** P=0.056N P=0.140N P=0.004N** | |COCH-ARM / FISHERS | P=0.006N** P=0.095N P=0.277N P=0.003N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 3 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Brain | | Astrocytoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.82 1/37.19 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 2.7% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 600 541 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.077N P=0.448N P=0.158N P=0.301N | |POLY 3 | P=0.077N P=0.445N P=0.181N P=0.235N | |POLY 1.5 | P=0.080N P=0.464N P=0.198N P=0.231N | |POLY 6 | P=0.069N P=0.429N P=0.165N P=0.254N | |LOGISTIC REGRESSION| P=0.082N P=0.480N P=0.185N P=0.240N | |COCH-ARM / FISHERS | P=0.086N P=0.500N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.073N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/53 (2%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 3/32.80 1/37.19 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 9.2% 2.7% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 201 541 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.030N* P=0.270N P=0.080N P=0.156N | |POLY 3 | P=0.029N* P=0.260N P=0.080N P=0.121N | |POLY 1.5 | P=0.031N* P=0.276N P=0.092N P=0.117N | |POLY 6 | P=0.025N* P=0.245N P=0.069N P=0.138N | |LOGISTIC REGRESSION| P=0.043N* P=0.338N P=0.177N P=0.128N | |COCH-ARM / FISHERS | P=0.034N* P=0.309N P=0.121N P=0.121N | |ORDER RESTRICTED | P=0.021N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 4 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Heart | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/53 (4%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.37 2/36.86 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 0.0% 5.4% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 680 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.471N P=0.303 (e) (e) | |POLY 3 | P=0.376N P=0.274 (e) (e) | |POLY 1.5 | P=0.395N P=0.261 (e) (e) | |POLY 6 | P=0.352N P=0.287 (e) (e) | |LOGISTIC REGRESSION| P=0.432N P=0.282 (e) (e) | |COCH-ARM / FISHERS | P=0.429N P=0.252 (e) (e) | |ORDER RESTRICTED | P=0.281N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Nephroblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/53 (0%) 0/52 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 1/32.37 0/36.61 0/41.53 2/33.85 | |POLY-3 PERCENT (g) | 3.1% 0.0% 0.0% 5.9% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 176 --- --- 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.276 P=0.504N P=0.496N P=0.509 | |POLY 3 | P=0.271 P=0.475N P=0.451N P=0.516 | |POLY 1.5 | P=0.272 P=0.485N P=0.469N P=0.517 | |POLY 6 | P=0.270 P=0.467N P=0.431N P=0.493 | |LOGISTIC REGRESSION| P=0.214 P=0.494N P=0.849N P=0.435 | |COCH-ARM / FISHERS | P=0.269 P=0.500N P=0.505N P=0.500 | |ORDER RESTRICTED | P=0.132 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 5 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiocarcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 5/53 (9%) 6/51 (12%) 22/53 (42%) | |POLY-3 RATE (b) | 0/31.38 5/36.89 6/42.75 22/36.46 | |POLY-3 PERCENT (g) | 0.0% 13.6% 14.0% 60.3% | |TERMINAL (d) | 0/15 (0%) 3/16 (19%) 1/23 (4%) 6/7 (86%) | |FIRST INCIDENCE | --- 659 618 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.047 * P=0.068 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.045 * P=0.040 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.039 * P=0.028 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.050 P=0.060 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.052 P=0.026 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.028 * P=0.012 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/53 (4%) 4/51 (8%) 7/53 (13%) | |POLY-3 RATE (b) | 1/31.38 2/36.68 4/41.43 7/33.51 | |POLY-3 PERCENT (g) | 3.2% 5.5% 9.7% 20.9% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 4/23 (17%) 2/7 (29%) | |FIRST INCIDENCE | 727 (T) 709 727 (T) 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.547 P=0.323 P=0.009 ** | |POLY 3 | P=0.010 * P=0.554 P=0.274 P=0.033 * | |POLY 1.5 | P=0.010 * P=0.535 P=0.235 P=0.034 * | |POLY 6 | P=0.008 ** P=0.573 P=0.319 P=0.027 * | |LOGISTIC REGRESSION| P=0.004 ** P=0.579 P=0.323 P=0.027 * | |COCH-ARM / FISHERS | P=0.010 * P=0.500 P=0.170 P=0.030 * | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 6 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocholangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/51 (0%) 3/53 (6%) | |POLY-3 RATE (b) | 0/31.38 0/36.61 0/41.43 3/32.40 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 9.3% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- 660 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** (e) (e) P=0.068 | |POLY 3 | P=0.013 * (e) (e) P=0.122 | |POLY 1.5 | P=0.013 * (e) (e) P=0.124 | |POLY 6 | P=0.014 * (e) (e) P=0.109 | |LOGISTIC REGRESSION| P=0.009 ** (e) (e) P=0.100 | |COCH-ARM / FISHERS | P=0.014 * (e) (e) P=0.121 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Cystic Keratinizing Epithelioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/53 (2%) 11/51 (22%) 35/51 (69%) | |POLY-3 RATE (b) | 0/31.38 1/36.61 11/42.26 35/41.94 | |POLY-3 PERCENT (g) | 0.0% 2.7% 26.0% 83.5% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 5/23 (22%) 6/7 (86%) | |FIRST INCIDENCE | --- 727 (T) 588 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.513 P=0.009 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.531 P=0.002 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.520 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.540 P=0.005 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.513 P=0.004 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 7 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 1/51 (2%) 2/51 (4%) | |POLY-3 RATE (b) | 0/31.38 0/36.61 1/41.13 2/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 6.3% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 727 (T) 555 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.046 * (e) P=0.585 P=0.265 | |POLY 3 | P=0.064 (e) P=0.553 P=0.239 | |POLY 1.5 | P=0.065 (e) P=0.532 P=0.238 | |POLY 6 | P=0.059 (e) P=0.575 P=0.229 | |LOGISTIC REGRESSION| P=0.063 (e) P=0.585 P=0.230 | |COCH-ARM / FISHERS | P=0.064 (e) P=0.490 P=0.238 | |ORDER RESTRICTED | P=0.075 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.38 1/36.61 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 6.4% 2.7% 0.0% 0.0% | |TERMINAL (d) | 2/15 (13%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.095N P=0.477N P=0.149N P=0.416N | |POLY 3 | P=0.076N P=0.446N P=0.178N P=0.232N | |POLY 1.5 | P=0.080N P=0.465N P=0.197N P=0.229N | |POLY 6 | P=0.069N P=0.429N P=0.160N P=0.248N | |LOGISTIC REGRESSION| P=0.095N P=0.477N (e) (e) | |COCH-ARM / FISHERS | P=0.086N P=0.500N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.071N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 8 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 6/53 (11%) 0/53 (0%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 6/32.44 0/36.61 1/42.13 1/32.91 | |POLY-3 PERCENT (g) | 18.5% 0.0% 2.4% 3.0% | |TERMINAL (d) | 3/15 (20%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 400 --- 727 (T) 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.035N* P=0.012N* P=0.015N* P=0.160N | |POLY 3 | P=0.025N* P=0.009N** P=0.024N* P=0.049N* | |POLY 1.5 | P=0.026N* P=0.011N* P=0.032N* P=0.048N* | |POLY 6 | P=0.023N* P=0.007N** P=0.017N* P=0.059N | |LOGISTIC REGRESSION| P=0.030N* P=0.011N* P=0.024N* P=0.058N | |COCH-ARM / FISHERS | P=0.029N* P=0.013N* P=0.056N P=0.056N | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 7/53 (13%) 1/53 (2%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 7/32.44 1/36.61 1/42.13 1/32.91 | |POLY-3 PERCENT (g) | 21.6% 2.7% 2.4% 3.0% | |TERMINAL (d) | 4/15 (27%) 1/16 (6%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 400 727 (T) 727 (T) 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015N* P=0.022N* P=0.006N** P=0.117N | |POLY 3 | P=0.009N** P=0.017N* P=0.010N* P=0.024N* | |POLY 1.5 | P=0.010N* P=0.021N* P=0.015N* P=0.024N* | |POLY 6 | P=0.008N** P=0.014N* P=0.007N** P=0.030N* | |LOGISTIC REGRESSION| P=0.011N* P=0.016N* P=0.009N** P=0.032N* | |COCH-ARM / FISHERS | P=0.012N* P=0.030N* P=0.030N* P=0.030N* | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 9 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 39/53 (74%) 39/53 (74%) 29/53 (55%) 11/53 (21%) | |POLY-3 RATE (b) | 39/45.19 39/48.22 29/46.84 11/35.90 | |POLY-3 PERCENT (g) | 86.3% 80.9% 61.9% 30.6% | |TERMINAL (d) | 11/15 (73%) 10/16 (63%) 14/23 (61%) 3/7 (43%) | |FIRST INCIDENCE | 309 247 440 258 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.250N P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P=0.327N P=0.004N** P<0.001N** | |POLY 1.5 | P<0.001N** P=0.387N P=0.005N** P<0.001N** | |POLY 6 | P<0.001N** P=0.304N P=0.006N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.445N P=0.004N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.587N P=0.034N* P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 40/53 (75%) 39/53 (74%) 29/53 (55%) 11/53 (21%) | |POLY-3 RATE (b) | 40/45.19 39/48.22 29/46.84 11/35.90 | |POLY-3 PERCENT (g) | 88.5% 80.9% 61.9% 30.6% | |TERMINAL (d) | 12/15 (80%) 10/16 (63%) 14/23 (61%) 3/7 (43%) | |FIRST INCIDENCE | 309 247 440 258 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.210N P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P=0.219N P=0.002N** P<0.001N** | |POLY 1.5 | P<0.001N** P=0.279N P=0.002N** P<0.001N** | |POLY 6 | P<0.001N** P=0.195N P=0.002N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.344N P=0.002N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.500N P=0.020N* P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 10 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 42/53 (79%) 39/53 (74%) 29/53 (55%) 12/53 (23%) | |POLY-3 RATE (b) | 42/46.17 39/48.22 29/46.84 12/36.90 | |POLY-3 PERCENT (g) | 91.0% 80.9% 61.9% 32.5% | |TERMINAL (d) | 12/15 (80%) 10/16 (63%) 14/23 (61%) 3/7 (43%) | |FIRST INCIDENCE | 309 247 440 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.143N P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P=0.121N P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P=0.149N P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P=0.118N P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.191N P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.324N P=0.006N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 2/53 (4%) 7/53 (13%) | |POLY-3 RATE (b) | 0/31.38 2/36.99 2/42.83 7/34.71 | |POLY-3 PERCENT (g) | 0.0% 5.4% 4.7% 20.2% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 618 498 523 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.280 P=0.328 P=0.011 * | |POLY 3 | P=0.002 ** P=0.275 P=0.312 P=0.010 * | |POLY 1.5 | P=0.002 ** P=0.261 P=0.285 P=0.009 ** | |POLY 6 | P=0.002 ** P=0.289 P=0.342 P=0.009 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.271 P=0.225 P=0.010 * | |COCH-ARM / FISHERS | P=0.002 ** P=0.248 P=0.248 P=0.006 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 11 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 2/53 (4%) 7/53 (13%) | |POLY-3 RATE (b) | 0/31.38 2/36.99 2/42.83 7/34.71 | |POLY-3 PERCENT (g) | 0.0% 5.4% 4.7% 20.2% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 618 498 523 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.280 P=0.328 P=0.011 * | |POLY 3 | P=0.002 ** P=0.275 P=0.312 P=0.010 * | |POLY 1.5 | P=0.002 ** P=0.261 P=0.285 P=0.009 ** | |POLY 6 | P=0.002 ** P=0.289 P=0.342 P=0.009 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.271 P=0.225 P=0.010 * | |COCH-ARM / FISHERS | P=0.002 ** P=0.248 P=0.248 P=0.006 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oral Mucosa | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 2/53 (4%) 7/53 (13%) | |POLY-3 RATE (b) | 0/31.38 2/36.99 2/42.83 7/34.71 | |POLY-3 PERCENT (g) | 0.0% 5.4% 4.7% 20.2% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 618 498 523 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.280 P=0.328 P=0.011 * | |POLY 3 | P=0.002 ** P=0.275 P=0.312 P=0.010 * | |POLY 1.5 | P=0.002 ** P=0.261 P=0.285 P=0.009 ** | |POLY 6 | P=0.002 ** P=0.289 P=0.342 P=0.009 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.271 P=0.225 P=0.010 * | |COCH-ARM / FISHERS | P=0.002 ** P=0.248 P=0.248 P=0.006 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 12 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 2/53 (4%) 0/52 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 1/31.35 2/36.63 0/41.53 0/30.95 | |POLY-3 PERCENT (g) | 3.2% 5.5% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 722 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.232N P=0.536 P=0.415N P=0.652N | |POLY 3 | P=0.162N P=0.554 P=0.445N P=0.503N | |POLY 1.5 | P=0.171N P=0.538 P=0.463N P=0.500N | |POLY 6 | P=0.149N P=0.572 P=0.424N P=0.516N | |LOGISTIC REGRESSION| P=0.208N P=0.571 (e) (e) | |COCH-ARM / FISHERS | P=0.186N P=0.515 P=0.495N P=0.500N | |ORDER RESTRICTED | P=0.200N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 2/53 (4%) 0/52 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 1/31.35 2/36.63 0/41.53 1/31.19 | |POLY-3 PERCENT (g) | 3.2% 5.5% 0.0% 3.2% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 722 --- 663 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.607N P=0.536 P=0.415N P=0.665 | |POLY 3 | P=0.452N P=0.554 P=0.445N P=0.761 | |POLY 1.5 | P=0.466N P=0.538 P=0.463N P=0.760N | |POLY 6 | P=0.429N P=0.572 P=0.424N P=0.750 | |LOGISTIC REGRESSION| P=0.539N P=0.571 (e) P=0.727 | |COCH-ARM / FISHERS | P=0.489N P=0.515 P=0.495N P=0.752N | |ORDER RESTRICTED | P=0.394N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 13 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/51 (29%) 22/53 (42%) 14/53 (26%) 6/53 (11%) | |POLY-3 RATE (b) | 15/32.57 22/39.95 14/43.88 6/32.96 | |POLY-3 PERCENT (g) | 46.1% 55.1% 31.9% 18.2% | |TERMINAL (d) | 9/15 (60%) 10/16 (63%) 7/23 (30%) 1/7 (14%) | |FIRST INCIDENCE | 603 531 588 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.044N* P=0.261 P=0.082N P=0.214N | |POLY 3 | P=0.002N** P=0.289 P=0.150N P=0.011N* | |POLY 1.5 | P=0.002N** P=0.221 P=0.234N P=0.011N* | |POLY 6 | P=0.002N** P=0.372 P=0.087N P=0.015N* | |LOGISTIC REGRESSION| P=0.003N** P=0.298 P=0.100N P=0.028N* | |COCH-ARM / FISHERS | P=0.005N** P=0.139 P=0.451N P=0.019N* | |ORDER RESTRICTED | P=0.004N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/51 (29%) 22/53 (42%) 15/53 (28%) 6/53 (11%) | |POLY-3 RATE (b) | 15/32.57 22/39.95 15/43.88 6/32.96 | |POLY-3 PERCENT (g) | 46.1% 55.1% 34.2% 18.2% | |TERMINAL (d) | 9/15 (60%) 10/16 (63%) 8/23 (35%) 1/7 (14%) | |FIRST INCIDENCE | 603 531 588 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.261 P=0.111N P=0.214N | |POLY 3 | P=0.002N** P=0.289 P=0.205N P=0.011N* | |POLY 1.5 | P=0.002N** P=0.221 P=0.304N P=0.011N* | |POLY 6 | P=0.003N** P=0.372 P=0.125N P=0.015N* | |LOGISTIC REGRESSION| P=0.003N** P=0.298 P=0.135N P=0.028N* | |COCH-ARM / FISHERS | P=0.006N** P=0.139 P=0.536N P=0.019N* | |ORDER RESTRICTED | P=0.004N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 14 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/52 (29%) 12/52 (23%) 12/50 (24%) 9/48 (19%) | |POLY-3 RATE (b) | 15/33.48 12/38.97 12/42.47 9/33.10 | |POLY-3 PERCENT (g) | 44.8% 30.8% 28.3% 27.2% | |TERMINAL (d) | 8/15 (53%) 3/16 (19%) 7/23 (30%) 1/7 (14%) | |FIRST INCIDENCE | 519 454 588 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.266N P=0.194N P=0.039N* P=0.431N | |POLY 3 | P=0.096N P=0.155N P=0.101N P=0.096N | |POLY 1.5 | P=0.109N P=0.215N P=0.173N P=0.115N | |POLY 6 | P=0.098N P=0.104N P=0.053N P=0.097N | |LOGISTIC REGRESSION| P=0.115N P=0.192N P=0.067N P=0.141N | |COCH-ARM / FISHERS | P=0.156N P=0.328N P=0.371N P=0.172N | |ORDER RESTRICTED | P=0.101N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/52 (0%) 2/50 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/31.37 0/35.79 2/41.02 0/29.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.431 (e) P=0.336 (e) | |POLY 3 | P=0.490 (e) P=0.302 (e) | |POLY 1.5 | P=0.511 (e) P=0.275 (e) | |POLY 6 | P=0.433 (e) P=0.333 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.336 (e) | |COCH-ARM / FISHERS | P=0.521 (e) P=0.238 (e) | |ORDER RESTRICTED | P=0.302 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 15 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/52 (29%) 12/52 (23%) 14/50 (28%) 9/48 (19%) | |POLY-3 RATE (b) | 15/33.48 12/38.97 14/42.47 9/33.10 | |POLY-3 PERCENT (g) | 44.8% 30.8% 33.0% 27.2% | |TERMINAL (d) | 8/15 (53%) 3/16 (19%) 9/23 (39%) 1/7 (14%) | |FIRST INCIDENCE | 519 454 588 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.316N P=0.194N P=0.081N P=0.431N | |POLY 3 | P=0.117N P=0.155N P=0.204N P=0.096N | |POLY 1.5 | P=0.130N P=0.215N P=0.311N P=0.115N | |POLY 6 | P=0.124N P=0.104N P=0.120N P=0.097N | |LOGISTIC REGRESSION| P=0.134N P=0.192N P=0.129N P=0.141N | |COCH-ARM / FISHERS | P=0.182N P=0.328N P=0.550N P=0.172N | |ORDER RESTRICTED | P=0.105N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 4/53 (8%) 8/53 (15%) 5/53 (9%) 4/53 (8%) | |POLY-3 RATE (b) | 4/31.79 8/37.70 5/42.23 4/32.95 | |POLY-3 PERCENT (g) | 12.6% 21.2% 11.8% 12.1% | |TERMINAL (d) | 2/15 (13%) 5/16 (31%) 4/23 (17%) 1/7 (14%) | |FIRST INCIDENCE | 660 541 700 621 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.483 P=0.250 P=0.491N P=0.440 | |POLY 3 | P=0.365N P=0.263 P=0.601N P=0.628N | |POLY 1.5 | P=0.372N P=0.230 P=0.617 P=0.623N | |POLY 6 | P=0.379N P=0.297 P=0.543N P=0.641 | |LOGISTIC REGRESSION| P=0.439N P=0.281 P=0.479N P=0.613 | |COCH-ARM / FISHERS | P=0.416N P=0.179 P=0.500 P=0.642N | |ORDER RESTRICTED | P=0.445N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 16 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 2/36.68 2/42.18 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 5.5% 4.7% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 709 714 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.600 P=0.277 P=0.361 (e) | |POLY 3 | P=0.523N P=0.273 P=0.308 (e) | |POLY 1.5 | P=0.521N P=0.260 P=0.283 (e) | |POLY 6 | P=0.546N P=0.285 P=0.337 (e) | |LOGISTIC REGRESSION| P=0.636N P=0.287 P=0.361 (e) | |COCH-ARM / FISHERS | P=0.541N P=0.248 P=0.248 (e) | |ORDER RESTRICTED | P=0.325N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 4/53 (8%) 10/53 (19%) 7/53 (13%) 4/53 (8%) | |POLY-3 RATE (b) | 4/31.79 10/37.77 7/42.29 4/32.95 | |POLY-3 PERCENT (g) | 12.6% 26.5% 16.6% 12.1% | |TERMINAL (d) | 2/15 (13%) 6/16 (38%) 5/23 (22%) 1/7 (14%) | |FIRST INCIDENCE | 660 541 700 621 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.463 P=0.123 P=0.575 P=0.440 | |POLY 3 | P=0.331N P=0.124 P=0.443 P=0.628N | |POLY 1.5 | P=0.338N P=0.103 P=0.379 P=0.623N | |POLY 6 | P=0.353N P=0.146 P=0.511 P=0.641 | |LOGISTIC REGRESSION| P=0.426N P=0.141 P=0.592 P=0.613 | |COCH-ARM / FISHERS | P=0.388N P=0.075 P=0.263 P=0.642N | |ORDER RESTRICTED | P=0.329N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 17 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 1/36.86 2/42.23 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 2.7% 4.7% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 658 700 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.571 P=0.562 P=0.358 (e) | |POLY 3 | P=0.617 P=0.532 P=0.309 (e) | |POLY 1.5 | P=0.634 P=0.521 P=0.283 (e) | |POLY 6 | P=0.560 P=0.543 P=0.337 (e) | |LOGISTIC REGRESSION| P=0.629 P=0.525 P=0.350 (e) | |COCH-ARM / FISHERS | P=0.632 P=0.500 P=0.248 (e) | |ORDER RESTRICTED | P=0.380N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.60 0/36.61 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 671 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.079N P=0.208N P=0.138N P=0.352N | |POLY 3 | P=0.083N P=0.205N P=0.179N P=0.233N | |POLY 1.5 | P=0.086N P=0.216N P=0.197N P=0.230N | |POLY 6 | P=0.073N P=0.196N P=0.163N P=0.251N | |LOGISTIC REGRESSION| P=0.072N P=0.191N P=0.151N P=0.277N | |COCH-ARM / FISHERS | P=0.087N P=0.248N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 18 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 1/53 (2%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 1/37.22 1/42.64 2/32.66 | |POLY-3 PERCENT (g) | 0.0% 2.7% 2.4% 6.1% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 531 573 611 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.136 P=0.534 P=0.566 P=0.230 | |POLY 3 | P=0.150 P=0.534 P=0.560 P=0.244 | |POLY 1.5 | P=0.151 P=0.522 P=0.540 P=0.246 | |POLY 6 | P=0.143 P=0.546 P=0.581 P=0.232 | |LOGISTIC REGRESSION| P=0.142 P=0.484 P=0.470 P=0.241 | |COCH-ARM / FISHERS | P=0.143 P=0.500 P=0.500 P=0.248 | |ORDER RESTRICTED | P=0.123 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 45/53 (85%) 46/53 (87%) 45/53 (85%) 42/53 (79%) | |POLY-3 RATE (b) | 45/45.97 46/49.09 45/47.95 42/45.75 | |POLY-3 PERCENT (g) | 97.9% 93.7% 93.8% 91.8% | |TERMINAL (d) | 15/15 (100%) 14/16 (88%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 309 247 440 258 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.253 P=0.258N P=0.007N** P=0.258 | |POLY 3 | P=0.125N P=0.285N P=0.270N P=0.135N | |POLY 1.5 | P=0.110N P=0.424N P=0.302N P=0.152N | |POLY 6 | P=0.223N P=0.218N P=0.362N P=0.188N | |LOGISTIC REGRESSION| P=0.062N P=0.454N P=0.020N* P=0.100N | |COCH-ARM / FISHERS | P=0.214N P=0.500 P=0.607N P=0.307N | |ORDER RESTRICTED | P=0.104N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 19 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 13/53 (25%) 16/53 (30%) 23/53 (43%) 33/53 (62%) | |POLY-3 RATE (b) | 13/35.14 16/40.41 23/46.99 33/43.01 | |POLY-3 PERCENT (g) | 37.0% 39.6% 48.9% 76.7% | |TERMINAL (d) | 5/15 (33%) 6/16 (38%) 10/23 (44%) 6/7 (86%) | |FIRST INCIDENCE | 176 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.509 P=0.370 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.502 P=0.192 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.433 P=0.109 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.584 P=0.323 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.385 P=0.049 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.332 P=0.032 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 49/53 (92%) 49/53 (92%) 50/53 (94%) 49/53 (92%) | |POLY-3 RATE (b) | 49/49.21 49/50.28 50/51.09 49/50.22 | |POLY-3 PERCENT (g) | 99.6% 97.5% 97.9% 97.6% | |TERMINAL (d) | 15/15 (100%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 176 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.135 P=0.215N P=0.012N* P=0.175 | |POLY 3 | P=0.355N P=0.481N P=0.576N P=0.504N | |POLY 1.5 | P=0.345N P=0.494N P=0.541N P=0.458N | |POLY 6 | P=0.506N P=0.499N P=0.896N P=0.750N | |LOGISTIC REGRESSION| P=0.461N P=0.470N P=0.299N P=0.541N | |COCH-ARM / FISHERS | P=0.540 P=0.642N P=0.500 P=0.642N | |ORDER RESTRICTED | P=0.280N (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).