TDMS Study 99039-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II DATE: 02/21/03
EXPERIMENT: 99039 TEST: 01 TIME: 10:23:41
TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-75408 ROUTE: DOSED FEED NTP C#: C99039
PATHOLOGIST: LANNING, LYNDA CAS: 55589-62-3
------------------------------------------------------------------------------------------------------------------------------------
FINAL#3/TG.AC MICE
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE 001 VEHICLE CONTROL
INCLUDE 002 0.3%
INCLUDE 003 1.0 %
INCLUDE 004 3.0 %
INCLUDE 006 VEHICLE CONTROL
INCLUDE 007 0.3 %
INCLUDE 008 1.0%
INCLUDE 009 3.0%
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II DATE: 02/21/03
EXPERIMENT: 99039 TEST: 01 TIME: 10:23:41
TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75408 ROUTE: DOSED FEED NTP C#: C99039
PATHOLOGIST: LANNING, LYNDA CAS: 55589-62-3
Mice(TG.AC HETEROZYGOUS TRANSGENIC)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE
BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.
---------------
Lung
Thyroid Gland
Urinary Bladder
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II DATE: 02/21/03
EXPERIMENT: 99039 TEST: 01 TIME: 10:23:41
TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75408 ROUTE: DOSED FEED NTP C#: C99039
PATHOLOGIST: LANNING, LYNDA CAS: 55589-62-3
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II
===============================================================
Male Mice
------------
Organ Morphology
----- ----------
Tooth Odontogenic Tumor
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
All Organs Malignant Tumors
===============================================================
Date: 02/21/03 EXPERIMENT: 99039 TEST: 01 Page 1
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 1/15 (7%) 1/15 (7%) 0/15 (0%) 2/15 (13%) |1/15 (7%) 0/0 (0%) 0/0 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 1/13.35 1/12.76 0/14.24 2/14.25 |1/13.86 0/0.00 0/0.00 1/13.60 |
|POLY-3 PERCENT (g) | 7.5% 7.8% 0.0% 14.0% |7.2% 0.0% 0.0% 7.4% |
|TERMINAL (d) | 1/13 (8%) 1/11 (9%) 0/13 (0%) 2/14 (14%) |1/12 (8%) 0/0 (0%) 0/0 (0%) 1/12 (8%) |
|FIRST INCIDENCE | 274 (T) 274 (T) --- 274 (T) |274 (T) --- --- 274 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.377 P=0.727 P=0.500N P=0.527 |P=0.685 P=1.000 P=1.000 P=0.765 |
|POLY 3 | P=0.351 P=0.752 P=0.487N P=0.523 |(e) (e) (e) P=0.757 |
|POLY 1.5 | P=0.346 P=0.753 P=0.490N P=0.517 |(e) (e) (e) P=0.757 |
|POLY 6 | P=0.354 P=0.749 P=0.487N P=0.526 |(e) (e) (e) P=0.760 |
|LOGISTIC REGRESSION| P=0.377 P=0.727 (e) P=0.527 |P=0.685 (e) (e) P=0.765 |
|COCH-ARM / FISHERS | P=0.329 P=0.759N P=0.500N P=0.500 |P=0.687 P=1.000 P=1.000 P=0.759N |
|ORDER RESTRICTED | P=0.290 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|Skin |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/15 (20%) 4/15 (27%) 8/15 (53%) 5/15 (33%) |3/15 (20%) 4/15 (27%) 6/15 (40%) 4/15 (27%) |
|POLY-3 RATE (b) | 3/13.35 4/12.76 8/14.34 5/14.25 |3/14.22 4/13.20 6/14.00 4/13.60 |
|POLY-3 PERCENT (g) | 22.5% 31.4% 55.8% 35.1% |21.1% 30.3% 42.9% 29.4% |
|TERMINAL (d) | 3/13 (23%) 4/11 (36%) 7/13 (54%) 5/14 (36%) |2/12 (17%) 4/12 (33%) 6/12 (50%) 4/12 (33%) |
|FIRST INCIDENCE | 274 (T) 274 (T) 264 274 (T) |236 274 (T) 274 (T) 274 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.467 P=0.398 P=0.073 P=0.385 |P=0.505 P=0.494 P=0.213 P=0.494 |
|POLY 3 | P=0.429 P=0.473 P=0.075 P=0.381 |P=0.489 P=0.456 P=0.201 P=0.473 |
|POLY 1.5 | P=0.407 P=0.476 P=0.070 P=0.370 |P=0.499 P=0.462 P=0.206 P=0.481 |
|POLY 6 | P=0.443 P=0.466 P=0.077 P=0.386 |P=0.482 P=0.457 P=0.197 P=0.469 |
|LOGISTIC REGRESSION| P=0.430 P=0.398 P=0.077 P=0.385 |P=0.510 P=0.473 P=0.218 P=0.490 |
|COCH-ARM / FISHERS | P=0.345 P=0.500 P=0.064 P=0.341 |P=0.507 P=0.500 P=0.213 P=0.500 |
|ORDER RESTRICTED | P=0.159 (e) (e) (e) |P=0.309 (e) (e) (e) |
|=================================================================================================================================|
Date: 02/21/03 EXPERIMENT: 99039 TEST: 01 Page 2
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 5/15 (33%) 4/15 (27%) 2/15 (13%) 6/15 (40%) |9/15 (60%) 7/15 (47%) 9/15 (60%) 8/15 (53%) |
|POLY-3 RATE (b) | 5/13.35 4/13.14 2/14.24 6/14.25 |9/14.31 7/13.20 9/14.43 8/13.60 |
|POLY-3 PERCENT (g) | 37.5% 30.4% 14.1% 42.1% |62.9% 53.0% 62.4% 58.8% |
|TERMINAL (d) | 5/13 (39%) 3/11 (27%) 2/13 (15%) 6/14 (43%) |8/12 (67%) 7/12 (58%) 7/12 (58%) 8/12 (67%) |
|FIRST INCIDENCE | 274 (T) 233 274 (T) 274 (T) |224 274 (T) 232 274 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.424 P=0.603N P=0.193N P=0.562 |P=0.555N P=0.362N P=0.631N P=0.505N |
|POLY 3 | P=0.359 P=0.511N P=0.164N P=0.554 |P=0.581N P=0.446N P=0.637N P=0.567N |
|POLY 1.5 | P=0.351 P=0.517N P=0.171N P=0.539 |P=0.565N P=0.432N P=0.642N P=0.545N |
|POLY 6 | P=0.362 P=0.505N P=0.164N P=0.561 |P=0.589 P=0.443N P=0.621N P=0.581N |
|LOGISTIC REGRESSION| P=0.379 P=0.531N P=0.193N P=0.562 |P=0.556N P=0.391N P=0.641N P=0.509N |
|COCH-ARM / FISHERS | P=0.319 P=0.500N P=0.195N P=0.500 |P=0.555N P=0.358N P=0.645N P=0.500N |
|ORDER RESTRICTED | P=0.311 (e) (e) (e) |P=0.623N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|Tooth |
| Odontogenic Tumor |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 4/15 (27%) 3/15 (20%) 0/15 (0%) 1/15 (7%) |2/15 (13%) 0/15 (0%) 6/15 (40%) 3/15 (20%) |
|POLY-3 RATE (b) | 4/15.00 3/14.97 0/14.24 1/14.25 |2/14.22 0/13.20 6/14.96 3/14.81 |
|POLY-3 PERCENT (g) | 26.7% 20.0% 0.0% 7.0% |14.1% 0.0% 40.1% 20.3% |
|TERMINAL (d) | 2/13 (15%) 0/11 (0%) 0/13 (0%) 1/14 (7%) |1/12 (8%) 0/12 (0%) 4/12 (33%) 1/12 (8%) |
|FIRST INCIDENCE | 148 71 --- 274 (T) |236 --- 207 156 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.113N P=0.542N P=0.063N P=0.163N |P=0.283 P=0.248N P=0.128 P=0.493 |
|POLY 3 | P=0.118N P=0.501N P=0.051N P=0.179N |P=0.319 P=0.248N P=0.120 P=0.519 |
|POLY 1.5 | P=0.115N P=0.501N P=0.049N* P=0.173N |P=0.301 P=0.246N P=0.113 P=0.511 |
|POLY 6 | P=0.119N P=0.502N P=0.054N P=0.183N |P=0.337 P=0.247N P=0.130 P=0.530 |
|LOGISTIC REGRESSION| P=0.218N P=0.239N P=0.089N P=0.238N |P=0.257 P=0.218N P=0.086 P=0.567 |
|COCH-ARM / FISHERS | P=0.115N P=0.500N P=0.050N P=0.165N |P=0.267 P=0.241N P=0.107 P=0.500 |
|ORDER RESTRICTED | P=0.046N* (e) (e) (e) |P=0.076 (e) (e) (e) |
|=================================================================================================================================|
Date: 02/21/03 EXPERIMENT: 99039 TEST: 01 Page 3
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|All Organs |
| Leukemia: Erythrocytic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 1/15 (7%) |2/15 (13%) 1/15 (7%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/13.35 0/12.76 1/14.89 1/15.00 |2/14.67 1/13.84 0/14.00 1/13.79 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 6.7% |13.6% 7.2% 0.0% 7.3% |
|TERMINAL (d) | 0/13 (0%) 0/11 (0%) 0/13 (0%) 0/14 (0%) |0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) |
|FIRST INCIDENCE | --- --- 192 172 |224 196 --- 255 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.325 (e) P=0.529 P=0.529 |P=0.504N P=0.533N P=0.256N P=0.507N |
|POLY 3 | P=0.352 (e) P=0.522 P=0.523 |P=0.501N P=0.521N P=0.242N P=0.522N |
|POLY 1.5 | P=0.338 (e) P=0.515 P=0.516 |P=0.499N P=0.519N P=0.238N P=0.515N |
|POLY 6 | P=0.362 (e) P=0.525 P=0.527 |P=0.504N P=0.520N P=0.247N P=0.527N |
|LOGISTIC REGRESSION| P=0.125 (e) P=0.261 P=0.259 |P=0.521N P=0.343N P=0.134N P=0.396N |
|COCH-ARM / FISHERS | P=0.301 (e) P=0.500 P=0.500 |P=0.500N P=0.500N P=0.241N P=0.500N |
|ORDER RESTRICTED | P=0.274 (e) (e) (e) |P=0.241N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 9/15 (60%) 8/15 (53%) 9/15 (60%) 9/15 (60%) |11/15 (73%) 9/15 (60%) 10/15 (67%) 10/15 (67%) |
|POLY-3 RATE (b) | 9/13.35 8/13.14 9/14.34 9/14.25 |11/14.67 9/13.20 10/14.43 10/13.60 |
|POLY-3 PERCENT (g) | 67.4% 60.9% 62.7% 63.2% |75.0% 68.2% 69.3% 73.5% |
|TERMINAL (d) | 9/13 (69%) 7/11 (64%) 8/13 (62%) 9/14 (64%) |9/12 (75%) 9/12 (75%) 8/12 (67%) 10/12 (83%) |
|FIRST INCIDENCE | 274 (T) 233 264 274 (T) |224 274 (T) 232 274 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.450N P=0.603 P=0.641N P=0.553N |P=0.567N P=0.365N P=0.504N P=0.512N |
|POLY 3 | P=0.561N P=0.521N P=0.555N P=0.564N |P=0.569 P=0.509N P=0.528N P=0.635N |
|POLY 1.5 | P=0.580N P=0.531N P=0.579N P=0.588N |P=0.594N P=0.470N P=0.519N P=0.585N |
|POLY 6 | P=0.553N P=0.510N P=0.547N P=0.553N |P=0.533 P=0.537N P=0.532N P=0.664 |
|LOGISTIC REGRESSION| P=0.528N P=0.558N P=0.568N P=0.553N |P=0.572N P=0.424N P=0.497N P=0.537N |
|COCH-ARM / FISHERS | P=0.520 P=0.500N P=0.645N P=0.645N |P=0.565N P=0.350N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.609N (e) (e) (e) |P=0.609N (e) (e) (e) |
|=================================================================================================================================|
Date: 02/21/03 EXPERIMENT: 99039 TEST: 01 Page 4
Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 1/15 (7%) |3/15 (20%) 1/15 (7%) 0/15 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 0/13.35 0/12.76 1/14.89 1/15.00 |3/15.00 1/13.84 0/14.00 2/13.79 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 6.7% |20.0% 7.2% 0.0% 14.5% |
|TERMINAL (d) | 0/13 (0%) 0/11 (0%) 0/13 (0%) 0/14 (0%) |0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8%) |
|FIRST INCIDENCE | --- --- 192 172 |224 196 --- 255 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.325 (e) P=0.529 P=0.529 |P=0.620N P=0.334N P=0.133N P=0.506N |
|POLY 3 | P=0.352 (e) P=0.522 P=0.523 |P=0.623N P=0.329N P=0.119N P=0.540N |
|POLY 1.5 | P=0.338 (e) P=0.515 P=0.516 |P=0.620N P=0.323N P=0.113N P=0.526N |
|POLY 6 | P=0.362 (e) P=0.525 P=0.527 |P=0.627N P=0.333N P=0.127N P=0.553N |
|LOGISTIC REGRESSION| P=0.125 (e) P=0.261 P=0.259 |P=0.639N P=0.162N P=0.048N* P=0.423N |
|COCH-ARM / FISHERS | P=0.301 (e) P=0.500 P=0.500 |P=0.623N P=0.299N P=0.112N P=0.500N |
|ORDER RESTRICTED | P=0.274 (e) (e) (e) |P=0.206N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | VEHICLE 0.3% 1.0 % 3.0 % |VEHICLE 0.3 % 1.0% 3.0% |
| | CONTROL |CONTROL |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 12/15 (80%) 10/15 (67%) 10/15 (67%) 10/15 (67%) |13/15 (87%) 10/15 (67%) 13/15 (87%) 13/15 (87%) |
|POLY-3 RATE (b) | 12/15.00 10/14.97 10/15.00 10/15.00 |13/15.00 10/13.84 13/15.00 13/15.00 |
|POLY-3 PERCENT (g) | 80.0% 66.8% 66.7% 66.7% |86.7% 72.3% 86.7% 86.7% |
|TERMINAL (d) | 10/13 (77%) 7/11 (64%) 8/13 (62%) 9/14 (64%) |10/12 (83%) 9/12 (75%) 10/12 (83%) 10/12 (83%) |
|FIRST INCIDENCE | 148 71 192 172 |224 196 207 156 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.240N P=0.565N P=0.357N P=0.271N |P=0.394 P=0.257N P=0.623 P=0.623 |
|POLY 3 | P=0.392N P=0.346N P=0.343N P=0.343N |P=0.443 P=0.311N P=0.698 P=0.698 |
|POLY 1.5 | P=0.393N P=0.345N P=0.343N P=0.343N |P=0.426 P=0.285N P=0.698 P=0.698 |
|POLY 6 | P=0.390N P=0.350N P=0.343N P=0.343N |P=0.457 P=0.332N P=0.698 P=0.698 |
|LOGISTIC REGRESSION| P=0.481N P=0.287N (e) (e) |P=0.356 P=0.248N (e) (e) |
|COCH-ARM / FISHERS | P=0.391N P=0.341N P=0.341N P=0.341N |P=0.353 P=0.195N P=0.701N P=0.701N |
|ORDER RESTRICTED | P=0.347N (e) (e) (e) |P=0.484 (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).