TDMS Study 99033-02 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 02 TIME: 11:37:28 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: C99033 PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/P53 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 02 TIME: 11:37:28 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: C99033 PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II (ASPA =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Atrophy Kidney Nephropathy Liver Inflammation Chronic Liver: Hepatocyte, Periportal Vacuolization Cytoplasmic Diffuse Spleen Atrophy Hematopoietic Cell Proliferation Thymus Atrophy Focal =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex: Subcapsular Hyperplasia Focal Lymph Node, Mandibular Hyperplasia Hyperplasia Lymphoid Thymus Atrophy Focal =============================================================== Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/15 (93%) 14/15 (93%) 12/15 (80%) 12/15 (80%) 10/15 (67%) 13/15 (87%) | |POLY-3 RATE (b) | 14/14.05 14/15.00 12/13.52 12/15.00 10/14.01 13/14.02 | |POLY-3 PERCENT (g) | 99.6% 93.3% 88.7% 80.0% 71.4% 92.7% | |TERMINAL (d) | 14/14 (100%) 14/15 (93%) 12/13 (92%) 12/15 (80%) 10/14 (71%) 13/14 (93%) | |FIRST INCIDENCE | 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.321N P=0.514N P=0.485N P=0.128N P=0.056N P=0.500N | |POLY 3 | P=0.352N P=0.534N P=0.321N P=0.126N P=0.047N* P=0.513N | |POLY 1.5 | P=0.368N P=0.599N P=0.274N P=0.151N P=0.054N P=0.535N | |POLY 6 | P=0.332N P=0.515N P=0.406N P=0.119N P=0.044N* P=0.501N | |LOGISTIC REGRESSION| P=0.321N P=0.514N P=0.485N P=0.128N P=0.056N P=0.500N | |COCH-ARM / FISHERS | P=0.312N P=0.759N P=0.299N P=0.299N P=0.084N P=0.500N | |ORDER RESTRICTED | P=0.110N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 3/15 (20%) 2/15 (13%) 1/15 (7%) 3/15 (20%) | |POLY-3 RATE (b) | 0/14.05 1/15.00 3/13.52 2/15.00 1/14.01 3/14.02 | |POLY-3 PERCENT (g) | 0.0% 6.7% 22.2% 13.3% 7.1% 21.4% | |TERMINAL (d) | 0/14 (0%) 1/15 (7%) 3/13 (23%) 2/15 (13%) 1/14 (7%) 3/14 (21%) | |FIRST INCIDENCE | --- 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.170 P=0.514 P=0.102 P=0.251 P=0.500 P=0.115 | |POLY 3 | P=0.164 P=0.513 P=0.098 P=0.247 P=0.499 P=0.105 | |POLY 1.5 | P=0.164 P=0.511 P=0.101 P=0.244 P=0.498 P=0.104 | |POLY 6 | P=0.164 P=0.514 P=0.094 P=0.248 P=0.500 P=0.105 | |LOGISTIC REGRESSION| (e) P=0.514 P=0.102 P=0.251 P=0.500 P=0.115 | |COCH-ARM / FISHERS | P=0.174 P=0.500 P=0.112 P=0.241 P=0.500 P=0.112 | |ORDER RESTRICTED | P=0.062 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 2/15 (13%) 1/15 (7%) 2/15 (13%) 1/15 (7%) | |POLY-3 RATE (b) | 1/14.05 0/15.00 2/13.52 1/15.00 2/14.01 1/14.02 | |POLY-3 PERCENT (g) | 7.1% 0.0% 14.8% 6.7% 14.3% 7.1% | |TERMINAL (d) | 1/14 (7%) 0/15 (0%) 2/13 (15%) 1/15 (7%) 2/14 (14%) 1/14 (7%) | |FIRST INCIDENCE | 274 (T) --- 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.500 P=0.486N P=0.473 P=0.749N P=0.500 P=0.764 | |POLY 3 | P=0.483 P=0.487N P=0.486 P=0.746N P=0.499 P=0.760 | |POLY 1.5 | P=0.485 P=0.489N P=0.493 P=0.749N P=0.496 P=0.759 | |POLY 6 | P=0.483 P=0.486N P=0.479 P=0.745N P=0.500 P=0.761 | |LOGISTIC REGRESSION| P=0.500 (e) P=0.473 P=0.749N P=0.500 P=0.764 | |COCH-ARM / FISHERS | P=0.505 P=0.500N P=0.500 P=0.759N P=0.500 P=0.759N | |ORDER RESTRICTED | P=0.451 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/15 (80%) 13/15 (87%) 13/14 (93%) 15/15 (100%) 15/15 (100%) 15/15 (100%) | |POLY-3 RATE (b) | 12/14.00 13/14.05 13/14.00 15/15.00 15/15.00 15/15.00 | |POLY-3 PERCENT (g) | 85.7% 92.6% 92.9% 100.0% 100.0% 100.0% | |TERMINAL (d) | 12/14 (86%) 13/14 (93%) 13/14 (93%) 15/15 (100%) 15/15 (100%) 15/15 (100%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.095 P=0.500 P=0.500 P=0.221 P=0.221 P=0.221 | |POLY 3 | P=0.096 P=0.509 P=0.500 P=0.215 P=0.215 P=0.215 | |POLY 1.5 | P=0.083 P=0.534 P=0.490 P=0.206 P=0.206 P=0.206 | |POLY 6 | P=0.099 P=0.500 P=0.500 P=0.216 P=0.216 P=0.216 | |LOGISTIC REGRESSION| P=0.095 P=0.500 P=0.250 P=0.221 P=0.221 P=0.221 | |COCH-ARM / FISHERS | P=0.037 * P=0.500 P=0.326 P=0.112 P=0.112 P=0.112 | |ORDER RESTRICTED | P=0.050 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/15 (33%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 5/14.05 0/0.00 0/0.00 0/0.00 0/0.00 1/14.02 | |POLY-3 PERCENT (g) | 35.6% 0.0% 0.0% 0.0% 0.0% 7.1% | |TERMINAL (d) | 5/14 (36%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/14 (7%) | |FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.057N P=1.000 P=1.000N P=1.000 P=1.000N P=0.087N | |POLY 3 | (e) (e) (e) (e) (e) P=0.079N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.080N | |POLY 6 | (e) (e) (e) (e) (e) P=0.078N | |LOGISTIC REGRESSION| P=0.057N (e) (e) (e) (e) P=0.087N | |COCH-ARM / FISHERS | P=0.055N P=1.000 P=1.000 P=1.000 P=1.000 P=0.084N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 1/14.00 0/0.00 0/0.00 0/0.00 0/0.00 3/15.00 | |POLY-3 PERCENT (g) | 7.1% 0.0% 0.0% 0.0% 0.0% 20.0% | |TERMINAL (d) | 1/14 (7%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/15 (20%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.235 P=1.000 P=1.000N P=1.000N P=1.000 P=0.324 | |POLY 3 | (e) (e) (e) (e) (e) P=0.324 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.323 | |POLY 6 | (e) (e) (e) (e) (e) P=0.324 | |LOGISTIC REGRESSION| P=0.235 (e) (e) (e) (e) P=0.324 | |COCH-ARM / FISHERS | P=0.210 P=1.000 P=1.000 P=1.000 P=1.000 P=0.299 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/14 (29%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 4/14.00 0/15.00 0/13.52 0/15.00 0/14.00 3/14.02 | |POLY-3 PERCENT (g) | 28.6% 0.0% 0.0% 0.0% 0.0% 21.4% | |TERMINAL (d) | 4/14 (29%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 3/14 (21%) | |FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283 P=0.048N* P=0.065N P=0.048N* P=0.056N P=0.500N | |POLY 3 | P=0.292 P=0.037N* P=0.048N* P=0.037N* P=0.044N* P=0.499N | |POLY 1.5 | P=0.287 P=0.037N* P=0.044N* P=0.037N* P=0.044N* P=0.494N | |POLY 6 | P=0.295 P=0.037N* P=0.051N P=0.037N* P=0.044N* P=0.500N | |LOGISTIC REGRESSION| P=0.283 (e) (e) (e) (e) P=0.500N | |COCH-ARM / FISHERS | P=0.292 P=0.042N* P=0.042N* P=0.042N* P=0.049N* P=0.458N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.00 0/14.23 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 0/14 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/14.00 2/15.00 0/13.52 1/15.00 0/14.00 1/14.02 | |POLY-3 PERCENT (g) | 0.0% 13.3% 0.0% 6.7% 0.0% 7.1% | |TERMINAL (d) | 0/14 (0%) 2/15 (13%) 0/13 (0%) 1/15 (7%) 0/14 (0%) 1/14 (7%) | |FIRST INCIDENCE | --- 274 (T) --- 274 (T) --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.594 P=0.251 (e) P=0.514 (e) P=0.500 | |POLY 3 | P=0.599 P=0.247 (e) P=0.514 (e) P=0.500 | |POLY 1.5 | P=0.596 P=0.247 (e) P=0.514 (e) P=0.502 | |POLY 6 | P=0.601 P=0.247 (e) P=0.514 (e) P=0.500 | |LOGISTIC REGRESSION| (e) P=0.251 (e) P=0.514 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.602 P=0.259 (e) P=0.517 (e) P=0.517 | |ORDER RESTRICTED | P=0.340 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/14 (14%) 3/15 (20%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/14.00 2/14.00 3/14.23 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 7.1% 14.3% 21.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/14 (7%) 2/14 (14%) 3/14 (21%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.065N P=0.500 P=0.298 P=0.486N P=0.486N P=0.486N | |POLY 3 | P=0.061N P=0.500 P=0.303 P=0.486N P=0.486N P=0.486N | |POLY 1.5 | P=0.061N P=0.499 P=0.309 P=0.487N P=0.487N P=0.487N | |POLY 6 | P=0.062N P=0.500 P=0.299 P=0.486N P=0.486N P=0.486N | |LOGISTIC REGRESSION| P=0.065N P=0.500 P=0.298 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.069N P=0.473 P=0.299 P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.099N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 2/15.00 0/13.52 0/15.00 0/14.00 0/14.02 | |POLY-3 PERCENT (g) | 0.0% 13.3% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 2/15 (13%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) | |FIRST INCIDENCE | --- 274 (T) --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.289N P=0.251 (e) (e) (e) (e) | |POLY 3 | P=0.266N P=0.247 (e) (e) (e) (e) | |POLY 1.5 | P=0.270N P=0.247 (e) (e) (e) (e) | |POLY 6 | P=0.264N P=0.247 (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.251 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.285N P=0.259 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.190N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/15 (40%) 5/14 (36%) 2/15 (13%) 5/15 (33%) 4/15 (27%) 4/15 (27%) | |POLY-3 RATE (b) | 6/14.00 5/14.00 2/14.23 5/15.00 4/15.00 4/15.00 | |POLY-3 PERCENT (g) | 42.9% 35.7% 14.1% 33.3% 26.7% 26.7% | |TERMINAL (d) | 6/14 (43%) 5/14 (36%) 2/14 (14%) 5/15 (33%) 4/15 (27%) 4/15 (27%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.351N P=0.500N P=0.109N P=0.443N P=0.303N P=0.303N | |POLY 3 | P=0.358N P=0.500N P=0.096N P=0.444N P=0.304N P=0.304N | |POLY 1.5 | P=0.365N P=0.503N P=0.092N P=0.447N P=0.306N P=0.306N | |POLY 6 | P=0.354N P=0.500N P=0.100N P=0.444N P=0.303N P=0.303N | |LOGISTIC REGRESSION| P=0.351N P=0.500N P=0.109N P=0.443N P=0.303N P=0.303N | |COCH-ARM / FISHERS | P=0.391N P=0.558N P=0.107N P=0.500N P=0.350N P=0.350N | |ORDER RESTRICTED | P=0.278N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 2/15 (13%) 4/15 (27%) 1/15 (7%) 2/14 (14%) 5/15 (33%) | |POLY-3 RATE (b) | 2/14.05 2/15.00 4/13.52 1/15.00 2/14.00 5/14.02 | |POLY-3 PERCENT (g) | 14.2% 13.3% 29.6% 6.7% 14.3% 35.7% | |TERMINAL (d) | 2/14 (14%) 2/15 (13%) 4/13 (31%) 1/15 (7%) 2/14 (14%) 5/14 (36%) | |FIRST INCIDENCE | 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.115 P=0.676N P=0.289 P=0.475N P=0.702 P=0.196 | |POLY 3 | P=0.110 P=0.674N P=0.306 P=0.477N P=0.698 P=0.192 | |POLY 1.5 | P=0.111 P=0.679N P=0.315 P=0.481N P=0.693 P=0.190 | |POLY 6 | P=0.111 P=0.673N P=0.297 P=0.476N P=0.699 P=0.193 | |LOGISTIC REGRESSION| P=0.115 P=0.676N P=0.289 P=0.475N P=0.702 P=0.196 | |COCH-ARM / FISHERS | P=0.116 P=0.701N P=0.326 P=0.500N P=0.674 P=0.195 | |ORDER RESTRICTED | P=0.114 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 3/15 (20%) 4/15 (27%) 6/15 (40%) 4/15 (27%) 4/15 (27%) | |POLY-3 RATE (b) | 4/14.00 3/14.05 4/14.23 6/15.00 4/15.00 4/15.00 | |POLY-3 PERCENT (g) | 28.6% 21.4% 28.1% 40.0% 26.7% 26.7% | |TERMINAL (d) | 4/14 (29%) 3/14 (21%) 4/14 (29%) 6/15 (40%) 4/15 (27%) 4/15 (27%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.538N P=0.500N P=0.659 P=0.401 P=0.616N P=0.616N | |POLY 3 | P=0.538N P=0.498N P=0.647N P=0.402 P=0.614N P=0.614N | |POLY 1.5 | P=0.547N P=0.493N P=0.639N P=0.399 P=0.616N P=0.616N | |POLY 6 | P=0.534N P=0.500N P=0.655N P=0.402 P=0.614N P=0.614N | |LOGISTIC REGRESSION| P=0.538N P=0.500N P=0.659 P=0.401 P=0.616N P=0.616N | |COCH-ARM / FISHERS | P=0.537 P=0.500N P=0.659N P=0.350 P=0.659N P=0.659N | |ORDER RESTRICTED | P=0.646 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 4/15.00 0/15.00 0/13.52 0/15.00 0/14.00 1/14.02 | |POLY-3 PERCENT (g) | 26.7% 0.0% 0.0% 0.0% 0.0% 7.1% | |TERMINAL (d) | 3/14 (21%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 1/14 (7%) | |FIRST INCIDENCE | 102 --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.321N P=0.055N P=0.068N P=0.055N P=0.064N P=0.179N | |POLY 3 | P=0.286N P=0.045N* P=0.058N P=0.045N* P=0.053N P=0.184N | |POLY 1.5 | P=0.291N P=0.045N* P=0.054N P=0.045N* P=0.053N P=0.182N | |POLY 6 | P=0.282N P=0.045N* P=0.062N P=0.045N* P=0.053N P=0.185N | |LOGISTIC REGRESSION| P=0.278N (e) P=0.043N* (e) (e) P=0.150N | |COCH-ARM / FISHERS | P=0.318N P=0.050N P=0.050N P=0.050N P=0.057N P=0.165N | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.23 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 2/14.05 1/15.00 0/13.52 0/15.00 0/14.00 1/14.02 | |POLY-3 PERCENT (g) | 14.2% 6.7% 0.0% 0.0% 0.0% 7.1% | |TERMINAL (d) | 2/14 (14%) 1/15 (7%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 1/14 (7%) | |FIRST INCIDENCE | 274 (T) 274 (T) --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.516N P=0.475N P=0.252N P=0.221N P=0.236N P=0.500N | |POLY 3 | P=0.506N P=0.477N P=0.240N P=0.216N P=0.232N P=0.501N | |POLY 1.5 | P=0.509N P=0.481N P=0.236N P=0.219N P=0.235N P=0.502N | |POLY 6 | P=0.503N P=0.476N P=0.244N P=0.216N P=0.231N P=0.500N | |LOGISTIC REGRESSION| P=0.516N P=0.475N (e) (e) (e) P=0.500N | |COCH-ARM / FISHERS | P=0.517N P=0.500N P=0.241N P=0.241N P=0.259N P=0.500N | |ORDER RESTRICTED | P=0.098N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.23 0/15.00 0/15.00 1/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 6.7% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |FIRST INCIDENCE | --- --- --- --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.113 (e) (e) (e) (e) P=0.514 | |POLY 3 | P=0.111 (e) (e) (e) (e) P=0.514 | |POLY 1.5 | P=0.110 (e) (e) (e) (e) P=0.513 | |POLY 6 | P=0.112 (e) (e) (e) (e) P=0.514 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.514 | |COCH-ARM / FISHERS | P=0.105 (e) (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.074 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.05 0/15.00 0/13.52 0/15.00 0/14.00 0/14.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.23 0/15.00 2/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 13.3% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- 275 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.430 (e) (e) (e) P=0.251 (e) | |POLY 3 | P=0.438 (e) (e) (e) P=0.248 (e) | |POLY 1.5 | P=0.434 (e) (e) (e) P=0.247 (e) | |POLY 6 | P=0.440 (e) (e) (e) P=0.248 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.251 (e) | |COCH-ARM / FISHERS | P=0.414 (e) (e) (e) P=0.241 (e) | |ORDER RESTRICTED | P=0.190 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte, Periportal | | Vacuolization Cytoplasmic Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 4/15 (27%) | |POLY-3 RATE (b) | 2/14.05 0/15.00 0/13.52 0/15.00 0/14.00 4/14.02 | |POLY-3 PERCENT (g) | 14.2% 0.0% 0.0% 0.0% 0.0% 28.5% | |TERMINAL (d) | 2/14 (14%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 4/14 (29%) | |FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.012 * P=0.221N P=0.252N P=0.221N P=0.236N P=0.326 | |POLY 3 | P=0.009 ** P=0.216N P=0.240N P=0.216N P=0.232N P=0.325 | |POLY 1.5 | P=0.009 ** P=0.219N P=0.236N P=0.219N P=0.235N P=0.323 | |POLY 6 | P=0.009 ** P=0.216N P=0.244N P=0.216N P=0.231N P=0.326 | |LOGISTIC REGRESSION| P=0.012 * (e) (e) (e) (e) P=0.326 | |COCH-ARM / FISHERS | P=0.013 * P=0.241N P=0.241N P=0.241N P=0.259N P=0.326 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte, Periportal | | Vacuolization Cytoplasmic Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.23 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lung: Perivascular | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/14 (14%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.05 0/15.00 0/13.52 0/15.00 2/14.00 0/14.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 14.3% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 2/14 (14%) 0/14 (0%) | |FIRST INCIDENCE | --- --- --- --- 274 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.412 (e) (e) (e) P=0.236 (e) | |POLY 3 | P=0.380 (e) (e) (e) P=0.230 (e) | |POLY 1.5 | P=0.381 (e) (e) (e) P=0.227 (e) | |POLY 6 | P=0.382 (e) (e) (e) P=0.231 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.236 (e) | |COCH-ARM / FISHERS | P=0.411 (e) (e) (e) P=0.224 (e) | |ORDER RESTRICTED | P=0.173 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lung: Perivascular | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 3/15 (20%) 0/14 (0%) 2/15 (13%) 0/14 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 1/14.00 3/15.00 0/12.52 2/15.00 0/14.00 2/14.02 | |POLY-3 PERCENT (g) | 7.1% 20.0% 0.0% 13.3% 0.0% 14.3% | |TERMINAL (d) | 1/14 (7%) 3/15 (20%) 0/12 (0%) 2/15 (13%) 0/14 (0%) 2/14 (14%) | |FIRST INCIDENCE | 274 (T) 274 (T) --- 274 (T) --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.565 P=0.324 P=0.531N P=0.525 P=0.500N P=0.500 | |POLY 3 | P=0.578 P=0.324 P=0.522N P=0.524 P=0.500N P=0.500 | |POLY 1.5 | P=0.574 P=0.324 P=0.516N P=0.524 P=0.500N P=0.503 | |POLY 6 | P=0.582 P=0.324 P=0.527N P=0.524 P=0.500N P=0.500 | |LOGISTIC REGRESSION| P=0.565 P=0.324 (e) P=0.525 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.575 P=0.326 P=0.500N P=0.527 P=0.500N P=0.527 | |ORDER RESTRICTED | P=0.477 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 2/13 (15%) 0/13 (0%) 1/15 (7%) 1/15 (7%) 0/14 (0%) | |POLY-3 RATE (b) | 3/14.00 2/13.00 0/12.23 1/15.00 1/15.00 0/14.00 | |POLY-3 PERCENT (g) | 21.4% 15.4% 0.0% 6.7% 6.7% 0.0% | |TERMINAL (d) | 3/14 (21%) 2/13 (15%) 0/12 (0%) 1/15 (7%) 1/15 (7%) 0/14 (0%) | |FIRST INCIDENCE | 275 (T) 275 (T) --- 275 (T) 275 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.085N P=0.536N P=0.143N P=0.273N P=0.273N P=0.115N | |POLY 3 | P=0.085N P=0.535N P=0.130N P=0.273N P=0.273N P=0.105N | |POLY 1.5 | P=0.087N P=0.537N P=0.126N P=0.274N P=0.274N P=0.106N | |POLY 6 | P=0.084N P=0.535N P=0.133N P=0.273N P=0.273N P=0.105N | |LOGISTIC REGRESSION| P=0.085N P=0.536N (e) P=0.273N P=0.273N (e) | |COCH-ARM / FISHERS | P=0.091N P=0.572N P=0.139N P=0.299N P=0.299N P=0.125N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/15.00 0/12.52 0/15.00 0/14.00 0/14.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/12 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/13 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/15.00 0/13.00 0/12.23 0/15.00 0/15.00 0/14.00 | |POLY-3 PERCENT (g) | 13.3% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/14 (7%) 0/13 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) | |FIRST INCIDENCE | 36 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201N P=0.256N P=0.257N P=0.232N P=0.232N P=0.240N | |POLY 3 | P=0.190N P=0.265N P=0.280N P=0.232N P=0.232N P=0.247N | |POLY 1.5 | P=0.191N P=0.265N P=0.275N P=0.232N P=0.232N P=0.247N | |POLY 6 | P=0.189N P=0.265N P=0.283N P=0.232N P=0.232N P=0.247N | |LOGISTIC REGRESSION| P=0.413N (e) P=0.378N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.200N P=0.278N P=0.278N P=0.241N P=0.241N P=0.259N | |ORDER RESTRICTED | P=0.010N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/13 (0%) 0/13 (0%) 0/11 (0%) 0/8 (0%) 0/10 (0%) 0/12 (0%) | |POLY-3 RATE (b) | 0/13.00 0/13.00 0/10.07 0/8.00 0/10.00 0/12.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/10 (0%) 0/8 (0%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/9 (0%) 0/14 (0%) 1/13 (8%) 0/14 (0%) 2/11 (18%) 2/14 (14%) | |POLY-3 RATE (b) | 0/9.00 0/14.00 1/13.00 0/14.00 2/11.00 2/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.7% 0.0% 18.2% 14.3% | |TERMINAL (d) | 0/9 (0%) 0/14 (0%) 1/13 (8%) 0/14 (0%) 2/11 (18%) 2/14 (14%) | |FIRST INCIDENCE | --- --- 275 (T) --- 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062 (e) P=0.573 (e) P=0.280 P=0.338 | |POLY 3 | P=0.060 (e) P=0.573 (e) P=0.275 P=0.336 | |POLY 1.5 | P=0.060 (e) P=0.573 (e) P=0.275 P=0.336 | |POLY 6 | P=0.060 (e) P=0.573 (e) P=0.275 P=0.336 | |LOGISTIC REGRESSION| (e) (e) P=0.573 (e) P=0.280 P=0.338 | |COCH-ARM / FISHERS | P=0.060 (e) P=0.591 (e) P=0.289 P=0.360 | |ORDER RESTRICTED | P=0.141 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/15 (60%) 1/1 (100%) 0/1 (0%) 0/0 (0%) 1/1 (100%) 10/15 (67%) | |POLY-3 RATE (b) | 9/14.05 1/1.00 0/0.45 0/0.00 1/1.00 10/14.02 | |POLY-3 PERCENT (g) | 64.1% 100.0% 0.0% 0.0% 100.0% 71.3% | |TERMINAL (d) | 9/14 (64%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 10/14 (71%) | |FIRST INCIDENCE | 274 (T) 274 (T) --- --- 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.462 P=0.638 P=1.000 P=1.000 P=0.638 P=0.500 | |POLY 3 | (e) P=0.638 P=0.681N (e) P=0.638 P=0.496 | |POLY 1.5 | (e) P=0.632 P=0.580N (e) P=0.632 P=0.490 | |POLY 6 | (e) P=0.640 P=0.784N (e) P=0.640 P=0.500 | |LOGISTIC REGRESSION| P=0.462 P=0.638 (e) (e) P=0.638 P=0.500 | |COCH-ARM / FISHERS | P=0.403 P=0.625 P=0.438N P=1.000 P=0.625 P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/15 (40%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/15 (53%) | |POLY-3 RATE (b) | 6/14.00 0/0.00 0/0.00 0/0.00 0/0.00 8/15.00 | |POLY-3 PERCENT (g) | 42.9% 0.0% 0.0% 0.0% 0.0% 53.3% | |TERMINAL (d) | 6/14 (43%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/15 (53%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.355 P=1.000 P=1.000 P=1.000 P=1.000 P=0.425 | |POLY 3 | (e) (e) (e) (e) (e) P=0.426 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.423 | |POLY 6 | (e) (e) (e) (e) (e) P=0.426 | |LOGISTIC REGRESSION| P=0.355 (e) (e) (e) (e) P=0.425 | |COCH-ARM / FISHERS | P=0.292 P=1.000 P=1.000 P=1.000 P=1.000 P=0.358 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 2/14.05 0/15.00 0/13.52 0/15.00 0/14.00 0/14.02 | |POLY-3 PERCENT (g) | 14.2% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/14 (14%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) | |FIRST INCIDENCE | 274 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.207N P=0.221N P=0.252N P=0.221N P=0.236N P=0.236N | |POLY 3 | P=0.201N P=0.216N P=0.240N P=0.216N P=0.232N P=0.231N | |POLY 1.5 | P=0.202N P=0.219N P=0.236N P=0.219N P=0.235N P=0.233N | |POLY 6 | P=0.200N P=0.216N P=0.244N P=0.216N P=0.231N P=0.231N | |LOGISTIC REGRESSION| P=0.207N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.208N P=0.241N P=0.241N P=0.241N P=0.259N P=0.241N | |ORDER RESTRICTED | P=0.008N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/14.05 0/14.23 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 0/14.05 0/15.00 0/13.52 0/15.00 1/14.00 2/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 7.1% 13.3% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 1/14 (7%) 1/14 (7%) | |FIRST INCIDENCE | --- --- --- --- 274 (T) 71 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * (e) (e) (e) P=0.500 P=0.240 | |POLY 3 | P=0.015 * (e) (e) (e) P=0.499 P=0.247 | |POLY 1.5 | P=0.015 * (e) (e) (e) P=0.497 P=0.244 | |POLY 6 | P=0.015 * (e) (e) (e) P=0.500 P=0.248 | |LOGISTIC REGRESSION| P=0.026 * (e) (e) (e) P=0.500 P=0.233 | |COCH-ARM / FISHERS | P=0.014 * (e) (e) (e) P=0.483 P=0.241 | |ORDER RESTRICTED | P=0.034 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 4/15 (27%) 1/15 (7%) 3/15 (20%) 1/15 (7%) 1/15 (7%) | |POLY-3 RATE (b) | 3/15.00 4/14.05 1/14.23 3/15.00 1/15.00 1/15.00 | |POLY-3 PERCENT (g) | 20.0% 28.5% 7.0% 20.0% 6.7% 6.7% | |TERMINAL (d) | 2/14 (14%) 4/14 (29%) 1/14 (7%) 3/15 (20%) 1/15 (7%) 1/15 (7%) | |FIRST INCIDENCE | 36 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.110N P=0.500 P=0.303N P=0.641N P=0.285N P=0.285N | |POLY 3 | P=0.116N P=0.461 P=0.318N P=0.670 P=0.298N P=0.298N | |POLY 1.5 | P=0.119N P=0.468 P=0.311N P=0.670 P=0.298N P=0.298N | |POLY 6 | P=0.115N P=0.460 P=0.323N P=0.670 P=0.298N P=0.298N | |LOGISTIC REGRESSION| P=0.163N P=0.479 P=0.374N P=0.641N P=0.285N P=0.285N | |COCH-ARM / FISHERS | P=0.124N P=0.500 P=0.299N P=0.674N P=0.299N P=0.299N | |ORDER RESTRICTED | P=0.148N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 2/14 (14%) | |POLY-3 RATE (b) | 0/14.00 0/15.00 0/13.52 0/14.00 0/14.01 2/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 14.3% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) 2/14 (14%) | |FIRST INCIDENCE | --- --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * (e) (e) (e) (e) P=0.236 | |POLY 3 | P=0.008 ** (e) (e) (e) (e) P=0.231 | |POLY 1.5 | P=0.008 ** (e) (e) (e) (e) P=0.231 | |POLY 6 | P=0.008 ** (e) (e) (e) (e) P=0.231 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.236 | |COCH-ARM / FISHERS | P=0.010 * (e) (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/13.00 0/14.00 0/14.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/13 (8%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.402N P=0.485N P=0.485N P=0.471N P=0.471N P=0.471N | |POLY 3 | P=0.424N P=0.485N P=0.485N P=0.471N P=0.471N P=0.471N | |POLY 1.5 | P=0.423N P=0.486N P=0.486N P=0.472N P=0.472N P=0.472N | |POLY 6 | P=0.424N P=0.485N P=0.485N P=0.471N P=0.471N P=0.471N | |LOGISTIC REGRESSION| P=0.402N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.406N P=0.500N P=0.500N P=0.483N P=0.483N P=0.483N | |ORDER RESTRICTED | P=0.047N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland | | Ectopic Thymus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 0/15.00 0/13.52 0/14.00 0/14.00 0/14.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) 0/14 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland | | Ectopic Thymus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/14 (14%) 1/13 (8%) 1/14 (7%) 3/14 (21%) 1/13 (8%) 2/15 (13%) | |POLY-3 RATE (b) | 2/13.00 1/13.00 1/13.23 3/14.00 1/13.00 2/15.00 | |POLY-3 PERCENT (g) | 15.4% 7.7% 7.6% 21.4% 7.7% 13.3% | |TERMINAL (d) | 2/13 (15%) 1/13 (8%) 1/13 (8%) 3/14 (21%) 1/13 (8%) 2/15 (13%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.575 P=0.500N P=0.500N P=0.536 P=0.500N P=0.648N | |POLY 3 | P=0.572 P=0.500N P=0.494N P=0.535 P=0.500N P=0.645N | |POLY 1.5 | P=0.568 P=0.501N P=0.488N P=0.534 P=0.501N P=0.647N | |POLY 6 | P=0.575 P=0.500N P=0.499N P=0.535 P=0.500N P=0.645N | |LOGISTIC REGRESSION| P=0.575 P=0.500N P=0.500N P=0.536 P=0.500N P=0.648N | |COCH-ARM / FISHERS | P=0.551 P=0.529N P=0.500N P=0.500 P=0.529N P=0.674N | |ORDER RESTRICTED | P=0.636N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II ( ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/15 (93%) 14/15 (93%) 15/15 (100%) 14/15 (93%) 15/15 (100%) 15/15 (100%) | |POLY-3 RATE (b) | 14/14.00 14/14.05 15/15.00 14/15.00 15/15.00 15/15.00 | |POLY-3 PERCENT (g) | 100.0% 99.7% 100.0% 93.3% 100.0% 100.0% | |TERMINAL (d) | 14/14 (100%) 14/14 (100%) 14/14 (100%) 14/15 (93%) 15/15 (100%) 15/15 (100%) | |FIRST INCIDENCE | 275 (T) 275 (T) 168 275 (T) 275 (T) 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.603N P=1.000N P=0.514 P=0.514N P=1.000N P=1.000N | |POLY 3 | P=0.673 P=1.000N P=1.000 P=0.515N P=1.000 P=1.000 | |POLY 1.5 | P=0.609 P=1.000N P=1.000 P=0.532N P=1.000 P=1.000 | |POLY 6 | P=0.686 P=1.000N P=1.000 P=0.514N P=1.000 P=1.000 | |LOGISTIC REGRESSION| P=0.715 P=1.000N (e) P=0.514N P=1.000N P=1.000N | |COCH-ARM / FISHERS | P=0.243 P=0.759N P=0.500 P=0.759N P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.528N (e) (e) (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).