TDMS Study 99033-03 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: 03 TIME: 11:44:18
TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: 99033B
PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0
------------------------------------------------------------------------------------------------------------------------------------
FINAL #3 TG:P16 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: 03 TIME: 11:44:18
TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: 99033B
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: Subcapsular Hyperplasia Focal
Kidney Nephropathy
Liver Infiltration Cellular Focal Lymphocyte
Inflammation Acute
Liver: Hepatocyte, Periportal Vacuolization Cytoplasmic
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
Kidney: Renal Tubule Dilatation Focal
Liver Hematopoietic Cell Proliferation
Necrosis Focal
Liver: Hepatocyte, Periportal Vacuolization Cytoplasmic
===============================================================
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 1
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - 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) | 2/15 (13%) 1/15 (7%) 0/15 (0%) 0/14 (0%) 1/15 (7%) 4/15 (27%) |
|POLY-3 RATE (b) | 2/14.01 1/14.61 0/15.00 0/14.00 1/14.00 4/15.00 |
|POLY-3 PERCENT (g) | 14.3% 6.9% 0.0% 0.0% 7.1% 26.7% |
|TERMINAL (d) | 2/14 (14%) 1/14 (7%) 0/15 (0%) 0/14 (0%) 1/14 (7%) 4/15 (27%) |
|FIRST INCIDENCE | 274 (T) 274 (T) --- --- 274 (T) 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.037 * P=0.500N P=0.221N P=0.236N P=0.500N P=0.360 |
|POLY 3 | P=0.028 * P=0.485N P=0.216N P=0.231N P=0.500N P=0.361 |
|POLY 1.5 | P=0.028 * P=0.484N P=0.217N P=0.233N P=0.502N P=0.357 |
|POLY 6 | P=0.029 * P=0.491N P=0.216N P=0.231N P=0.500N P=0.361 |
|LOGISTIC REGRESSION| P=0.037 * P=0.500N (e) (e) P=0.500N P=0.360 |
|COCH-ARM / FISHERS | P=0.032 * P=0.500N P=0.241N P=0.259N P=0.500N P=0.326 |
|ORDER RESTRICTED | P=0.029 * (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) | 14/15 (93%) 15/15 (100%) 12/13 (92%) 15/15 (100%) 15/15 (100%) 15/15 (100%) |
|POLY-3 RATE (b) | 14/14.00 15/15.00 12/13.00 15/15.00 15/15.00 15/15.00 |
|POLY-3 PERCENT (g) | 100.0% 100.0% 92.3% 100.0% 100.0% 100.0% |
|TERMINAL (d) | 13/13 (100%) 15/15 (100%) 12/13 (92%) 15/15 (100%) 15/15 (100%) 14/14 (100%) |
|FIRST INCIDENCE | 219 275 (T) 275 (T) 275 (T) 275 (T) 267 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.316 P=0.486N P=0.248N P=0.486N P=0.486N P=0.737N |
|POLY 3 | P=0.547 P=1.000 P=0.485N P=1.000 P=1.000 P=1.000 |
|POLY 1.5 | P=0.543 P=1.000 P=0.489N P=1.000 P=1.000 P=1.000 |
|POLY 6 | P=0.547 P=1.000 P=0.485N P=1.000 P=1.000 P=1.000 |
|LOGISTIC REGRESSION| P=0.564 P=0.486N P=0.456N P=0.486N P=0.486N (e) |
|COCH-ARM / FISHERS | P=0.281 P=0.500 P=0.722N P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.501 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 2
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Harderian Gland |
| Infiltration Cellular Lymphocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/15 (13%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 2/14.01 0/0.00 0/0.00 0/0.00 0/0.00 2/15.00 |
|POLY-3 PERCENT (g) | 14.3% 0.0% 0.0% 0.0% 0.0% 13.3% |
|TERMINAL (d) | 2/14 (14%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/15 (13%) |
|FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.576N P=1.000 P=1.000N P=1.000 P=1.000 P=0.676N |
|POLY 3 | (e) (e) (e) (e) (e) P=0.673N |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.676N |
|POLY 6 | (e) (e) (e) (e) (e) P=0.673N |
|LOGISTIC REGRESSION| P=0.576N (e) (e) (e) (e) P=0.676N |
|COCH-ARM / FISHERS | P=0.606 P=1.000 P=1.000 P=1.000 P=1.000 P=0.701N |
|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 Lymphocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/13.51 0/0.00 0/0.00 0/0.00 0/0.00 1/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 6.7% |
|TERMINAL (d) | 0/13 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/14 (7%) |
|FIRST INCIDENCE | --- --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.322 (e) (e) (e) (e) P=0.515 |
|POLY 3 | (e) (e) (e) (e) (e) P=0.520 |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.517 |
|POLY 6 | (e) (e) (e) (e) (e) P=0.522 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.515 |
|COCH-ARM / FISHERS | P=0.306 (e) (e) (e) (e) P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 3
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 7/15 (47%) |
|POLY-3 RATE (b) | 2/14.01 0/14.61 0/15.00 0/14.00 0/14.00 7/15.00 |
|POLY-3 PERCENT (g) | 14.3% 0.0% 0.0% 0.0% 0.0% 46.7% |
|TERMINAL (d) | 2/14 (14%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) 7/15 (47%) |
|FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.236N P=0.221N P=0.236N P=0.236N P=0.073 |
|POLY 3 | P<0.001 ** P=0.222N P=0.216N P=0.231N P=0.231N P=0.064 |
|POLY 1.5 | P<0.001 ** P=0.221N P=0.217N P=0.233N P=0.232N P=0.062 |
|POLY 6 | P<0.001 ** P=0.225N P=0.216N P=0.231N P=0.231N P=0.064 |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) (e) P=0.073 |
|COCH-ARM / FISHERS | P<0.001 ** P=0.241N P=0.241N P=0.259N P=0.241N P=0.054 |
|ORDER RESTRICTED | P<0.001 ** (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) | 1/15 (7%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 1/13.51 0/15.00 0/13.00 0/15.00 0/15.00 1/14.92 |
|POLY-3 PERCENT (g) | 7.4% 0.0% 0.0% 0.0% 0.0% 6.7% |
|TERMINAL (d) | 1/13 (8%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) |
|FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.421 P=0.471N P=0.500N P=0.471N P=0.471N P=0.748N |
|POLY 3 | P=0.411 P=0.479N P=0.508N P=0.479N P=0.479N P=0.738N |
|POLY 1.5 | P=0.413 P=0.482N P=0.511N P=0.482N P=0.482N P=0.741N |
|POLY 6 | P=0.408 P=0.475N P=0.504N P=0.475N P=0.475N P=0.735N |
|LOGISTIC REGRESSION| P=0.421 (e) (e) (e) (e) P=0.748N |
|COCH-ARM / FISHERS | P=0.422 P=0.500N P=0.536N P=0.500N P=0.500N P=0.759N |
|ORDER RESTRICTED | P=0.262N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 4
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.01 0/14.61 0/15.00 0/14.00 0/14.00 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%) 0/15 (0%) 0/14 (0%) 0/14 (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) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Dilatation Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 10/15 (67%) 7/15 (47%) 5/13 (38%) 5/15 (33%) 5/15 (33%) 9/15 (60%) |
|POLY-3 RATE (b) | 10/13.51 7/15.00 5/13.00 5/15.00 5/15.00 9/15.00 |
|POLY-3 PERCENT (g) | 74.1% 46.7% 38.5% 33.3% 33.3% 60.0% |
|TERMINAL (d) | 10/13 (77%) 7/15 (47%) 5/13 (39%) 5/15 (33%) 5/15 (33%) 8/14 (57%) |
|FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 267 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.466 P=0.110N P=0.060N P=0.029N* P=0.029N* P=0.392N |
|POLY 3 | P=0.493 P=0.133N P=0.066N P=0.029N* P=0.029N* P=0.348N |
|POLY 1.5 | P=0.490 P=0.146N P=0.074N P=0.033N* P=0.033N* P=0.372N |
|POLY 6 | P=0.497 P=0.118N P=0.057N P=0.024N* P=0.024N* P=0.322N |
|LOGISTIC REGRESSION| P=0.523 P=0.110N P=0.060N P=0.029N* P=0.029N* P=0.316N |
|COCH-ARM / FISHERS | P=0.466 P=0.231N P=0.133N P=0.072N P=0.072N P=0.500N |
|ORDER RESTRICTED | P=0.061N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 5
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.01 0/14.61 0/15.00 0/14.00 0/14.00 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%) 0/15 (0%) 0/14 (0%) 0/14 (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) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.55 0/15.00 0/15.00 2/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 13.3% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) |
|FIRST INCIDENCE | --- --- --- --- --- 267 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.013 * (e) (e) (e) (e) P=0.264 |
|POLY 3 | P=0.010 * (e) (e) (e) (e) P=0.256 |
|POLY 1.5 | P=0.010 * (e) (e) (e) (e) P=0.252 |
|POLY 6 | P=0.010 * (e) (e) (e) (e) P=0.261 |
|LOGISTIC REGRESSION| P=0.011 * (e) (e) (e) (e) P=0.245 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.241 |
|ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 6
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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) | 3/15 (20%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 3/14.01 0/14.61 0/15.00 0/14.00 0/14.00 1/15.00 |
|POLY-3 PERCENT (g) | 21.4% 0.0% 0.0% 0.0% 0.0% 6.7% |
|TERMINAL (d) | 3/14 (21%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) 1/15 (7%) |
|FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.463N P=0.115N P=0.104N P=0.115N P=0.115N P=0.273N |
|POLY 3 | P=0.502N P=0.098N P=0.094N P=0.105N P=0.105N P=0.273N |
|POLY 1.5 | P=0.502N P=0.097N P=0.095N P=0.106N P=0.106N P=0.275N |
|POLY 6 | P=0.499N P=0.100N P=0.093N P=0.105N P=0.105N P=0.273N |
|LOGISTIC REGRESSION| P=0.463N (e) P=0.100N (e) (e) P=0.273N |
|COCH-ARM / FISHERS | P=0.473N P=0.112N P=0.112N P=0.125N P=0.112N P=0.299N |
|ORDER RESTRICTED | P=0.005N** (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) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.55 0/15.00 0/15.00 1/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 6.7% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) |
|FIRST INCIDENCE | --- --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.107 (e) (e) (e) (e) P=0.515 |
|POLY 3 | P=0.111 (e) (e) (e) (e) P=0.520 |
|POLY 1.5 | P=0.110 (e) (e) (e) (e) P=0.517 |
|POLY 6 | P=0.111 (e) (e) (e) (e) P=0.522 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.515 |
|COCH-ARM / FISHERS | P=0.105 (e) (e) (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.078 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 7
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver |
| Inflammation Acute |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 2/14.01 0/14.61 0/15.00 0/14.00 0/14.00 0/15.00 |
|POLY-3 PERCENT (g) | 14.3% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 2/14 (14%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) 0/15 (0%) |
|FIRST INCIDENCE | 274 (T) --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.202N P=0.236N P=0.221N P=0.236N P=0.236N P=0.221N |
|POLY 3 | P=0.218N P=0.222N P=0.216N P=0.231N P=0.231N P=0.216N |
|POLY 1.5 | P=0.218N P=0.221N P=0.217N P=0.233N P=0.232N P=0.217N |
|POLY 6 | P=0.216N P=0.225N P=0.216N P=0.231N P=0.231N P=0.216N |
|LOGISTIC REGRESSION| P=0.202N (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.205N P=0.241N P=0.241N P=0.259N P=0.241N P=0.241N |
|ORDER RESTRICTED | P=0.006N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver |
| Inflammation Acute |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|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) | 0/13.51 0/15.00 0/13.55 0/15.00 0/15.00 0/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (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) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 8
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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%) 0/15 (0%) 3/15 (20%) 0/14 (0%) 1/15 (7%) 4/15 (27%) |
|POLY-3 RATE (b) | 2/14.01 0/14.61 3/15.00 0/14.00 1/14.00 4/15.00 |
|POLY-3 PERCENT (g) | 14.3% 0.0% 20.0% 0.0% 7.1% 26.7% |
|TERMINAL (d) | 2/14 (14%) 0/14 (0%) 3/15 (20%) 0/14 (0%) 1/14 (7%) 4/15 (27%) |
|FIRST INCIDENCE | 274 (T) --- 274 (T) --- 274 (T) 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.099 P=0.236N P=0.533 P=0.236N P=0.500N P=0.360 |
|POLY 3 | P=0.086 P=0.222N P=0.532 P=0.231N P=0.500N P=0.361 |
|POLY 1.5 | P=0.085 P=0.221N P=0.529 P=0.233N P=0.502N P=0.357 |
|POLY 6 | P=0.088 P=0.225N P=0.533 P=0.231N P=0.500N P=0.361 |
|LOGISTIC REGRESSION| P=0.099 (e) P=0.534 (e) P=0.500N P=0.360 |
|COCH-ARM / FISHERS | P=0.088 P=0.241N P=0.500 P=0.259N P=0.500N P=0.326 |
|ORDER RESTRICTED | P=0.071 (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%) 1/15 (7%) 2/15 (13%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.55 0/15.00 1/15.00 2/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 6.7% 13.4% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 1/15 (7%) 2/14 (14%) |
|FIRST INCIDENCE | --- --- --- --- 275 (T) 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.015 * (e) (e) (e) P=0.529 P=0.252 |
|POLY 3 | P=0.015 * (e) (e) (e) P=0.521 P=0.255 |
|POLY 1.5 | P=0.015 * (e) (e) (e) P=0.518 P=0.252 |
|POLY 6 | P=0.015 * (e) (e) (e) P=0.525 P=0.258 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.529 P=0.252 |
|COCH-ARM / FISHERS | P=0.014 * (e) (e) (e) P=0.500 P=0.241 |
|ORDER RESTRICTED | P=0.037 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 9
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver: Hepatocyte, Periportal |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 6/15 (40%) 11/15 (73%) 14/15 (93%) 8/14 (57%) 13/15 (87%) 13/15 (87%) |
|POLY-3 RATE (b) | 6/14.01 11/14.61 14/15.00 8/14.00 13/14.00 13/15.00 |
|POLY-3 PERCENT (g) | 42.8% 75.3% 93.3% 57.1% 92.9% 86.7% |
|TERMINAL (d) | 6/14 (43%) 11/14 (79%) 14/15 (93%) 8/14 (57%) 13/14 (93%) 13/15 (87%) |
|FIRST INCIDENCE | 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.047 * P=0.064 P=0.006 ** P=0.355 P=0.009 ** P=0.020 * |
|POLY 3 | P=0.034 * P=0.077 P=0.002 ** P=0.355 P=0.003 ** P=0.012 * |
|POLY 1.5 | P=0.031 * P=0.081 P=0.002 ** P=0.349 P=0.003 ** P=0.011 * |
|POLY 6 | P=0.036 * P=0.068 P=0.002 ** P=0.356 P=0.003 ** P=0.012 * |
|LOGISTIC REGRESSION| P=0.047 * P=0.064 P=0.006 ** P=0.353 P=0.009 ** P=0.020 * |
|COCH-ARM / FISHERS | P=0.034 * P=0.070 P=0.003 ** P=0.291 P=0.010 * P=0.010 * |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Liver: Hepatocyte, Periportal |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.55 0/15.00 0/15.00 2/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 13.4% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 2/14 (14%) |
|FIRST INCIDENCE | --- --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.011 * (e) (e) (e) (e) P=0.252 |
|POLY 3 | P=0.010 * (e) (e) (e) (e) P=0.255 |
|POLY 1.5 | P=0.010 * (e) (e) (e) (e) P=0.252 |
|POLY 6 | P=0.010 * (e) (e) (e) (e) P=0.258 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.252 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.241 |
|ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 10
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/14 (0%) 0/14 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.01 0/14.61 2/15.00 0/14.00 0/14.00 0/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 13.3% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/14 (0%) 0/14 (0%) 2/15 (13%) 0/14 (0%) 0/14 (0%) 0/15 (0%) |
|FIRST INCIDENCE | --- --- 274 (T) --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.374N (e) P=0.251 (e) (e) (e) |
|POLY 3 | P=0.364N (e) P=0.247 (e) (e) (e) |
|POLY 1.5 | P=0.367N (e) P=0.246 (e) (e) (e) |
|POLY 6 | P=0.361N (e) P=0.248 (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) P=0.251 (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.384N (e) P=0.241 (e) (e) (e) |
|ORDER RESTRICTED | P=0.361N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.06 0/15.00 0/15.00 1/13.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 7.2% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/15 (0%) 1/13 (8%) |
|FIRST INCIDENCE | --- --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.099 (e) (e) (e) (e) P=0.500 |
|POLY 3 | P=0.104 (e) (e) (e) (e) P=0.506 |
|POLY 1.5 | P=0.104 (e) (e) (e) (e) P=0.504 |
|POLY 6 | P=0.104 (e) (e) (e) (e) P=0.509 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.500 |
|COCH-ARM / FISHERS | P=0.102 (e) (e) (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.068 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 11
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Nose: Olfactory Epithelium |
| Hyaline Droplet |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.01 0/0.00 0/0.00 0/0.00 0/0.00 0/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/14 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (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) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Nose: Olfactory Epithelium |
| Hyaline Droplet |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/15 (13%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/15 (20%) |
|POLY-3 RATE (b) | 2/13.51 0/0.00 0/0.00 0/0.00 0/0.00 3/14.92 |
|POLY-3 PERCENT (g) | 14.8% 0.0% 0.0% 0.0% 0.0% 20.1% |
|TERMINAL (d) | 2/13 (15%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/14 (21%) |
|FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.439 P=1.000 P=1.000N P=1.000 P=1.000 P=0.536 |
|POLY 3 | (e) (e) (e) (e) (e) P=0.547 |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.541 |
|POLY 6 | (e) (e) (e) (e) (e) P=0.553 |
|LOGISTIC REGRESSION| P=0.439 (e) (e) (e) (e) P=0.536 |
|COCH-ARM / FISHERS | P=0.403 P=1.000 P=1.000 P=1.000 P=1.000 P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 12
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Nose: Respiratory Epithelium |
| Hyaline Droplet |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.01 0/0.00 0/0.00 0/0.00 0/0.00 0/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/14 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (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) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Nose: Respiratory Epithelium |
| Hyaline Droplet |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/15 (7%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 1/13.51 0/0.00 0/0.00 0/0.00 0/0.00 2/14.92 |
|POLY-3 PERCENT (g) | 7.4% 0.0% 0.0% 0.0% 0.0% 13.4% |
|TERMINAL (d) | 1/13 (8%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/14 (14%) |
|FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.408 P=1.000 P=1.000N P=1.000 P=1.000 P=0.527 |
|POLY 3 | (e) (e) (e) (e) (e) P=0.535 |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.531 |
|POLY 6 | (e) (e) (e) (e) (e) P=0.540 |
|LOGISTIC REGRESSION| P=0.408 (e) (e) (e) (e) P=0.527 |
|COCH-ARM / FISHERS | P=0.380 P=1.000 P=1.000 P=1.000 P=1.000 P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 13
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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) | 12/15 (80%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 11/15 (73%) |
|POLY-3 RATE (b) | 12/14.01 0/0.00 0/0.00 0/0.00 0/0.00 11/15.00 |
|POLY-3 PERCENT (g) | 85.6% 0.0% 0.0% 0.0% 0.0% 73.3% |
|TERMINAL (d) | 12/14 (86%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 11/15 (73%) |
|FIRST INCIDENCE | 274 (T) --- --- --- --- 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.280N P=1.000N P=1.000N P=1.000N P=1.000N P=0.360N |
|POLY 3 | (e) (e) (e) (e) (e) P=0.363N |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.377N |
|POLY 6 | (e) (e) (e) (e) (e) P=0.361N |
|LOGISTIC REGRESSION| P=0.280N (e) (e) (e) (e) P=0.360N |
|COCH-ARM / FISHERS | P=0.415N P=1.000 P=1.000 P=1.000 P=1.000 P=0.500N |
|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) | 4/15 (27%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 5/15 (33%) |
|POLY-3 RATE (b) | 4/13.51 0/0.00 0/0.00 0/0.00 0/0.00 5/14.92 |
|POLY-3 PERCENT (g) | 29.6% 0.0% 0.0% 0.0% 0.0% 33.5% |
|TERMINAL (d) | 4/13 (31%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 5/14 (36%) |
|FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.473 P=1.000N P=1.000N P=1.000 P=1.000 P=0.553 |
|POLY 3 | (e) (e) (e) (e) (e) P=0.569 |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.560 |
|POLY 6 | (e) (e) (e) (e) (e) P=0.579 |
|LOGISTIC REGRESSION| P=0.473 (e) (e) (e) (e) P=0.553 |
|COCH-ARM / FISHERS | P=0.421 P=1.000 P=1.000 P=1.000 P=1.000 P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 14
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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%) 1/15 (7%) 2/15 (13%) 3/14 (21%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/14.01 1/14.61 2/15.00 3/14.00 0/14.00 1/15.00 |
|POLY-3 PERCENT (g) | 0.0% 6.9% 13.3% 21.4% 0.0% 6.7% |
|TERMINAL (d) | 0/14 (0%) 1/14 (7%) 2/15 (13%) 3/14 (21%) 0/14 (0%) 1/15 (7%) |
|FIRST INCIDENCE | --- 274 (T) 274 (T) 274 (T) --- 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.506N P=0.500 P=0.251 P=0.115 (e) P=0.514 |
|POLY 3 | P=0.509N P=0.508 P=0.247 P=0.105 (e) P=0.514 |
|POLY 1.5 | P=0.513N P=0.509 P=0.246 P=0.103 (e) P=0.512 |
|POLY 6 | P=0.506N P=0.505 P=0.248 P=0.105 (e) P=0.514 |
|LOGISTIC REGRESSION| (e) P=0.500 P=0.251 P=0.115 (e) P=0.514 |
|COCH-ARM / FISHERS | P=0.521N P=0.500 P=0.241 P=0.100 (e) P=0.500 |
|ORDER RESTRICTED | P=0.272 (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) | 5/15 (33%) 2/15 (13%) 4/14 (29%) 3/15 (20%) 2/15 (13%) 3/15 (20%) |
|POLY-3 RATE (b) | 5/13.51 2/15.00 4/13.06 3/15.00 2/15.00 3/15.00 |
|POLY-3 PERCENT (g) | 37.0% 13.3% 30.6% 20.0% 13.3% 20.0% |
|TERMINAL (d) | 5/13 (39%) 2/15 (13%) 4/13 (31%) 3/15 (20%) 2/15 (13%) 2/14 (14%) |
|FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) 275 (T) 275 (T) 267 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.327N P=0.141N P=0.500N P=0.259N P=0.141N P=0.299N |
|POLY 3 | P=0.320N P=0.151N P=0.524N P=0.280N P=0.151N P=0.280N |
|POLY 1.5 | P=0.324N P=0.157N P=0.525N P=0.290N P=0.157N P=0.290N |
|POLY 6 | P=0.318N P=0.144N P=0.514N P=0.270N P=0.144N P=0.270N |
|LOGISTIC REGRESSION| P=0.301N P=0.141N P=0.500N P=0.259N P=0.141N P=0.275N |
|COCH-ARM / FISHERS | P=0.339N P=0.195N P=0.550N P=0.341N P=0.195N P=0.341N |
|ORDER RESTRICTED | P=0.171N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 15
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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) | 1/15 (7%) 2/14 (14%) 0/15 (0%) 0/13 (0%) 1/15 (7%) 0/15 (0%) |
|POLY-3 RATE (b) | 1/14.01 2/14.00 0/15.00 0/13.00 1/14.00 0/15.00 |
|POLY-3 PERCENT (g) | 7.1% 14.3% 0.0% 0.0% 7.1% 0.0% |
|TERMINAL (d) | 1/14 (7%) 2/14 (14%) 0/15 (0%) 0/13 (0%) 1/14 (7%) 0/15 (0%) |
|FIRST INCIDENCE | 274 (T) 274 (T) --- --- 274 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.259N P=0.500 P=0.486N P=0.515N P=0.764 P=0.486N |
|POLY 3 | P=0.260N P=0.500 P=0.486N P=0.515N P=0.761 P=0.486N |
|POLY 1.5 | P=0.260N P=0.497 P=0.488N P=0.516N P=0.759 P=0.488N |
|POLY 6 | P=0.260N P=0.500 P=0.486N P=0.515N P=0.761 P=0.486N |
|LOGISTIC REGRESSION| P=0.259N P=0.500 (e) (e) P=0.764 (e) |
|COCH-ARM / FISHERS | P=0.261N P=0.473 P=0.500N P=0.536N P=0.759N P=0.500N |
|ORDER RESTRICTED | P=0.143N (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) | 0/14 (0%) 1/15 (7%) 1/14 (7%) 0/14 (0%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/13.51 1/15.00 1/13.06 0/14.00 0/15.00 0/14.92 |
|POLY-3 PERCENT (g) | 0.0% 6.7% 7.7% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/13 (0%) 1/15 (7%) 1/13 (8%) 0/14 (0%) 0/15 (0%) 0/14 (0%) |
|FIRST INCIDENCE | --- 275 (T) 275 (T) --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.325N P=0.529 P=0.500 (e) (e) (e) |
|POLY 3 | P=0.322N P=0.521 P=0.493 (e) (e) (e) |
|POLY 1.5 | P=0.324N P=0.518 P=0.493 (e) (e) (e) |
|POLY 6 | P=0.319N P=0.525 P=0.496 (e) (e) (e) |
|LOGISTIC REGRESSION| (e) P=0.529 P=0.500 (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.323N P=0.517 P=0.500 (e) (e) (e) |
|ORDER RESTRICTED | P=0.365N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 16
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/13.01 0/14.61 0/15.00 0/14.00 0/14.00 0/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (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) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Thyroid Gland |
| Ectopic Thymus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/13.51 0/15.00 0/13.55 2/15.00 0/15.00 0/14.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.3% 0.0% 0.0% |
|TERMINAL (d) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 2/15 (13%) 0/15 (0%) 0/14 (0%) |
|FIRST INCIDENCE | --- --- --- 275 (T) --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.579N (e) (e) P=0.268 (e) (e) |
|POLY 3 | P=0.561N (e) (e) P=0.256 (e) (e) |
|POLY 1.5 | P=0.566N (e) (e) P=0.252 (e) (e) |
|POLY 6 | P=0.557N (e) (e) P=0.261 (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.268 (e) (e) |
|COCH-ARM / FISHERS | P=0.586N (e) (e) P=0.241 (e) (e) |
|ORDER RESTRICTED | P=0.384 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 03 Page 17
Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (A
SPA
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%) 13/15 (87%) 13/15 (87%) 15/15 (100%) 15/15 (100%) 14/15 (93%) |
|POLY-3 RATE (b) | 14/14.00 13/15.00 13/13.55 15/15.00 15/15.00 14/15.00 |
|POLY-3 PERCENT (g) | 100.0% 86.7% 96.0% 100.0% 100.0% 93.3% |
|TERMINAL (d) | 13/13 (100%) 13/15 (87%) 13/13 (100%) 15/15 (100%) 15/15 (100%) 13/14 (93%) |
|FIRST INCIDENCE | 219 275 (T) 275 (T) 275 (T) 275 (T) 267 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.531 P=0.134N P=0.515N P=0.486N P=0.486N P=0.484N |
|POLY 3 | P=0.656N P=0.248N P=0.816N P=1.000 P=1.000 P=0.514N |
|POLY 1.5 | P=0.616 P=0.250N P=0.535N P=1.000 P=1.000 P=0.518N |
|POLY 6 | P=0.625N P=0.248N P=0.999N P=1.000 P=1.000 P=0.514N |
|LOGISTIC REGRESSION| P=0.552N P=0.224N P=0.515N P=0.486N P=0.486N P=0.489N |
|COCH-ARM / FISHERS | P=0.350 P=0.500N P=0.500N P=0.500 P=0.500 P=0.759N |
|ORDER RESTRICTED | P=0.308N (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).