TDMS Study 99033-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/25/03
EXPERIMENT: 99033 TEST: 01 TIME: 09:00:46
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
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
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/25/03
EXPERIMENT: 99033 TEST: 01 TIME: 09:00:46
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
----- ----------
Stomach, Forestomach Squamous Cell Papilloma
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
Squamous Cell Papilloma
All Organs Benign Tumors
===============================================================
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 1
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
| Alveolar/Bronchiolar Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/14 (0%) 0/15 (0%) 2/14 (14%) 1/15 (7%) 2/14 (14%) 2/14 (14%) |
|POLY-3 RATE (b) | 0/12.30 0/14.31 2/10.17 1/13.78 2/12.66 2/11.92 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 19.7% 7.3% 15.8% 16.8% |
|TERMINAL (d) | 0/9 (0%) 0/12 (0%) 2/8 (25%) 1/12 (8%) 2/11 (18%) 2/10 (20%) |
|FIRST INCIDENCE | --- --- 274 (T) 274 (T) 274 (T) 274 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.128 (e) P=0.207 P=0.557 P=0.280 P=0.257 |
|POLY 3 | P=0.098 (e) P=0.187 P=0.523 P=0.236 P=0.222 |
|POLY 1.5 | P=0.108 (e) P=0.203 P=0.523 P=0.237 P=0.229 |
|POLY 6 | P=0.089 (e) P=0.175 P=0.521 P=0.234 P=0.215 |
|LOGISTIC REGRESSION| (e) (e) P=0.207 P=0.557 P=0.280 P=0.257 |
|COCH-ARM / FISHERS | P=0.119 (e) P=0.241 P=0.517 P=0.241 P=0.241 |
|ORDER RESTRICTED | P=0.136 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 1/15 (7%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) |
|POLY-3 RATE (b) | 1/13.08 0/12.09 0/9.99 0/10.85 0/13.80 0/9.94 |
|POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/11 (9%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) |
|FIRST INCIDENCE | 275 (T) --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.437N P=0.519N P=0.540N P=0.540N P=0.500N P=0.564N |
|POLY 3 | P=0.332N P=0.516N P=0.553N P=0.537N P=0.489N P=0.554N |
|POLY 1.5 | P=0.359N P=0.513N P=0.545N P=0.526N P=0.497N P=0.544N |
|POLY 6 | P=0.314N P=0.520N P=0.557N P=0.542N P=0.483N P=0.560N |
|LOGISTIC REGRESSION| P=0.437N (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.420N P=0.517N P=0.517N P=0.500N P=0.517N P=0.517N |
|ORDER RESTRICTED | P=0.112N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 2
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/12.59 0/14.31 2/11.64 0/13.78 1/13.57 1/12.09 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 17.2% 0.0% 7.4% 8.3% |
|TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) |
|FIRST INCIDENCE | --- --- 138 --- 138 271 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.375 (e) P=0.212 (e) P=0.500 P=0.483 |
|POLY 3 | P=0.326 (e) P=0.211 (e) P=0.515 P=0.492 |
|POLY 1.5 | P=0.344 (e) P=0.216 (e) P=0.510 P=0.497 |
|POLY 6 | P=0.314 (e) P=0.211 (e) P=0.518 P=0.488 |
|LOGISTIC REGRESSION| P=0.354 (e) P=0.302 (e) P=0.483 P=0.487 |
|COCH-ARM / FISHERS | P=0.378 (e) P=0.241 (e) P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.328 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Salivary Glands |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 0/13.08 0/12.12 0/10.06 1/11.80 0/13.80 1/10.04 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 8.5% 0.0% 10.0% |
|TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) |
|FIRST INCIDENCE | --- --- --- 97 --- 269 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.203 (e) (e) P=0.500 (e) P=0.443 |
|POLY 3 | P=0.204 (e) (e) P=0.480 (e) P=0.448 |
|POLY 1.5 | P=0.208 (e) (e) P=0.487 (e) P=0.460 |
|POLY 6 | P=0.204 (e) (e) P=0.476 (e) P=0.442 |
|LOGISTIC REGRESSION| P=0.276 (e) (e) (e) (e) P=0.443 |
|COCH-ARM / FISHERS | P=0.230 (e) (e) P=0.500 (e) P=0.500 |
|ORDER RESTRICTED | P=0.139 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 3
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|Skin |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/12.59 2/14.31 0/10.20 0/13.78 1/12.70 0/12.06 |
|POLY-3 PERCENT (g) | 0.0% 14.0% 0.0% 0.0% 7.9% 0.0% |
|TERMINAL (d) | 0/9 (0%) 2/12 (17%) 0/8 (0%) 0/12 (0%) 1/11 (9%) 0/10 (0%) |
|FIRST INCIDENCE | --- 274 (T) --- --- 274 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.428N P=0.300 (e) (e) P=0.540 (e) |
|POLY 3 | P=0.404N P=0.261 (e) (e) P=0.502 (e) |
|POLY 1.5 | P=0.410N P=0.254 (e) (e) P=0.501 (e) |
|POLY 6 | P=0.400N P=0.267 (e) (e) P=0.503 (e) |
|LOGISTIC REGRESSION| (e) P=0.300 (e) (e) P=0.540 (e) |
|COCH-ARM / FISHERS | P=0.436N P=0.241 (e) (e) P=0.500 (e) |
|ORDER RESTRICTED | P=0.312N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Skin |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 3/15 (20%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 0/15 (0%) |
|POLY-3 RATE (b) | 1/13.08 3/12.74 1/10.06 0/10.85 2/13.80 0/9.98 |
|POLY-3 PERCENT (g) | 7.7% 23.5% 9.9% 0.0% 14.5% 0.0% |
|TERMINAL (d) | 1/11 (9%) 2/10 (20%) 1/9 (11%) 0/9 (0%) 2/11 (18%) 0/8 (0%) |
|FIRST INCIDENCE | 275 (T) 198 275 (T) --- 275 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.255N P=0.270 P=0.720 P=0.540N P=0.500 P=0.564N |
|POLY 3 | P=0.244N P=0.286 P=0.700 P=0.537N P=0.519 P=0.553N |
|POLY 1.5 | P=0.237N P=0.288 P=0.715 P=0.526N P=0.507 P=0.540N |
|POLY 6 | P=0.245N P=0.285 P=0.694 P=0.542N P=0.530 P=0.560N |
|LOGISTIC REGRESSION| P=0.232N P=0.288 P=0.720 (e) P=0.500 (e) |
|COCH-ARM / FISHERS | P=0.212N P=0.299 P=0.759N P=0.500N P=0.500 P=0.500N |
|ORDER RESTRICTED | P=0.200N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 4
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 8/15 (53%) 5/15 (33%) 2/15 (13%) 5/15 (33%) 6/15 (40%) 6/15 (40%) |
|POLY-3 RATE (b) | 8/12.69 5/14.31 2/10.23 5/13.81 6/12.70 6/12.78 |
|POLY-3 PERCENT (g) | 63.0% 34.9% 19.6% 36.2% 47.3% 47.0% |
|TERMINAL (d) | 5/9 (56%) 5/12 (42%) 1/8 (13%) 4/12 (33%) 6/11 (55%) 5/10 (50%) |
|FIRST INCIDENCE | 271 274 (T) 271 271 274 (T) 180 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.450 P=0.100N P=0.068N P=0.122N P=0.241N P=0.318N |
|POLY 3 | P=0.456 P=0.139N P=0.039N* P=0.157N P=0.344N P=0.338N |
|POLY 1.5 | P=0.461 P=0.159N P=0.029N* P=0.171N P=0.348N P=0.333N |
|POLY 6 | P=0.449 P=0.127N P=0.049N* P=0.153N P=0.344N P=0.346N |
|LOGISTIC REGRESSION| P=0.377 P=0.115N P=0.054N P=0.148N P=0.349N P=0.393N |
|COCH-ARM / FISHERS | P=0.442 P=0.231N P=0.025N* P=0.231N P=0.358N P=0.358N |
|ORDER RESTRICTED | P=0.161N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 4/15 (27%) 9/15 (60%) 4/15 (27%) 7/15 (47%) 7/15 (47%) 5/15 (33%) |
|POLY-3 RATE (b) | 4/13.08 9/12.82 4/10.06 7/11.59 7/13.94 5/10.68 |
|POLY-3 PERCENT (g) | 30.6% 70.2% 39.8% 60.4% 50.2% 46.8% |
|TERMINAL (d) | 4/11 (36%) 7/10 (70%) 4/9 (44%) 5/9 (56%) 5/11 (46%) 4/8 (50%) |
|FIRST INCIDENCE | 275 (T) 192 275 (T) 184 267 184 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.448 P=0.049 * P=0.536 P=0.126 P=0.242 P=0.282 |
|POLY 3 | P=0.539 P=0.042 * P=0.493 P=0.136 P=0.261 P=0.352 |
|POLY 1.5 | P=0.547 P=0.046 * P=0.532 P=0.156 P=0.235 P=0.382 |
|POLY 6 | P=0.555 P=0.040 * P=0.474 P=0.133 P=0.288 P=0.345 |
|LOGISTIC REGRESSION| P=0.524 P=0.040 * P=0.536 P=0.116 P=0.284 P=0.321 |
|COCH-ARM / FISHERS | P=0.484N P=0.070 P=0.659N P=0.225 P=0.225 P=0.500 |
|ORDER RESTRICTED | P=0.219 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 5
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|Tooth |
| Odontogenic Tumor |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 3/15 (20%) 4/15 (27%) 2/15 (13%) 2/15 (13%) 2/15 (13%) 6/15 (40%) |
|POLY-3 RATE (b) | 3/13.64 4/15.00 2/10.23 2/13.81 2/12.83 6/14.14 |
|POLY-3 PERCENT (g) | 22.0% 26.7% 19.6% 14.5% 15.6% 42.4% |
|TERMINAL (d) | 0/9 (0%) 1/12 (8%) 1/8 (13%) 1/12 (8%) 1/11 (9%) 2/10 (20%) |
|FIRST INCIDENCE | 76 198 271 271 261 180 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.119 P=0.587 P=0.589N P=0.452N P=0.498N P=0.244 |
|POLY 3 | P=0.128 P=0.556 P=0.635N P=0.494N P=0.529N P=0.230 |
|POLY 1.5 | P=0.122 P=0.535 P=0.598N P=0.496N P=0.526N P=0.220 |
|POLY 6 | P=0.135 P=0.576 P=0.658N P=0.494N P=0.527N P=0.245 |
|LOGISTIC REGRESSION| P=0.114 P=0.317 P=0.487N P=0.611N P=0.503N P=0.211 |
|COCH-ARM / FISHERS | P=0.112 P=0.500 P=0.500N P=0.500N P=0.500N P=0.213 |
|ORDER RESTRICTED | P=0.128 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|Tooth |
| Odontogenic Tumor |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 4/15 (27%) 4/15 (27%) 2/15 (13%) 5/15 (33%) 5/15 (33%) 1/15 (7%) |
|POLY-3 RATE (b) | 4/15.00 4/12.74 2/11.25 5/13.16 5/14.00 1/10.68 |
|POLY-3 PERCENT (g) | 26.7% 31.4% 17.8% 38.0% 35.7% 9.4% |
|TERMINAL (d) | 0/11 (0%) 2/10 (20%) 0/9 (0%) 1/9 (11%) 2/11 (18%) 0/8 (0%) |
|FIRST INCIDENCE | 109 206 200 165 267 184 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.275N P=0.588 P=0.461N P=0.399 P=0.516 P=0.290N |
|POLY 3 | P=0.296N P=0.556 P=0.475N P=0.409 P=0.452 P=0.287N |
|POLY 1.5 | P=0.263N P=0.586 P=0.446N P=0.429 P=0.453 P=0.253N |
|POLY 6 | P=0.317N P=0.531 P=0.485N P=0.401 P=0.452 P=0.309N |
|LOGISTIC REGRESSION| P=0.161N P=0.615N P=0.177N P=0.626N P=0.500 P=0.062N |
|COCH-ARM / FISHERS | P=0.176N P=0.659N P=0.326N P=0.500 P=0.500 P=0.165N |
|ORDER RESTRICTED | P=0.228N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 6
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|All Organs |
| Leukemia: Erythrocytic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 0/15 (0%) 1/15 (7%) 2/15 (13%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 1/13.22 0/14.31 1/10.83 2/14.97 0/12.70 0/12.06 |
|POLY-3 PERCENT (g) | 7.6% 0.0% 9.2% 13.4% 0.0% 0.0% |
|TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) |
|FIRST INCIDENCE | 197 --- 197 199 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.284N P=0.471N P=0.727 P=0.560 P=0.500N P=0.516N |
|POLY 3 | P=0.296N P=0.484N P=0.716 P=0.544 P=0.508N P=0.518N |
|POLY 1.5 | P=0.285N P=0.487N P=0.730 P=0.533 P=0.505N P=0.509N |
|POLY 6 | P=0.305N P=0.483N P=0.707 P=0.552 P=0.511N P=0.527N |
|LOGISTIC REGRESSION| P=0.271N P=0.668N P=0.722N P=0.284 P=0.505N P=0.527N |
|COCH-ARM / FISHERS | P=0.267N P=0.500N P=0.759N P=0.500 P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.361N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Leukemia: Erythrocytic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 3/15 (20%) 1/15 (7%) 0/15 (0%) 0/15 (0%) 1/15 (7%) |
|POLY-3 RATE (b) | 1/14.01 3/13.98 1/10.91 0/10.85 0/13.80 1/10.50 |
|POLY-3 PERCENT (g) | 7.1% 21.5% 9.2% 0.0% 0.0% 9.5% |
|TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) |
|FIRST INCIDENCE | 109 192 148 --- --- 215 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.364N P=0.289 P=0.727 P=0.514N P=0.514N P=0.706 |
|POLY 3 | P=0.293N P=0.296 P=0.703 P=0.550N P=0.503N P=0.693 |
|POLY 1.5 | P=0.307N P=0.290 P=0.714 P=0.536N P=0.507N P=0.708 |
|POLY 6 | P=0.282N P=0.308 P=0.699 P=0.557N P=0.499N P=0.690 |
|LOGISTIC REGRESSION| P=0.239N P=0.366 P=0.512N P=0.337N P=0.341N P=0.607N |
|COCH-ARM / FISHERS | P=0.322N P=0.299 P=0.759N P=0.500N P=0.500N P=0.759N |
|ORDER RESTRICTED | P=0.281N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 7
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 8/15 (53%) 6/15 (40%) 3/15 (20%) 5/15 (33%) 8/15 (53%) 8/15 (53%) |
|POLY-3 RATE (b) | 8/12.69 6/14.31 3/10.23 5/13.81 8/12.70 8/12.78 |
|POLY-3 PERCENT (g) | 63.0% 41.9% 29.3% 36.2% 63.0% 62.6% |
|TERMINAL (d) | 5/9 (56%) 6/12 (50%) 2/8 (25%) 4/12 (33%) 8/11 (73%) 7/10 (70%) |
|FIRST INCIDENCE | 271 274 (T) 271 271 274 (T) 180 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.182 P=0.163N P=0.138N P=0.122N P=0.475N P=0.568N |
|POLY 3 | P=0.167 P=0.239N P=0.111N P=0.157N P=0.659N P=0.651N |
|POLY 1.5 | P=0.177 P=0.267N P=0.087N P=0.171N P=0.653N P=0.635N |
|POLY 6 | P=0.158 P=0.223N P=0.133N P=0.153N P=0.661 P=0.658 |
|LOGISTIC REGRESSION| P=0.114 P=0.199N P=0.135N P=0.148N P=0.649 P=0.597 |
|COCH-ARM / FISHERS | P=0.179 P=0.358N P=0.064N P=0.231N P=0.642N P=0.642N |
|ORDER RESTRICTED | P=0.277 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 4/15 (27%) 11/15 (73%) 5/15 (33%) 7/15 (47%) 8/15 (53%) 5/15 (33%) |
|POLY-3 RATE (b) | 4/13.08 11/13.45 5/10.06 7/11.59 8/13.94 5/10.68 |
|POLY-3 PERCENT (g) | 30.6% 81.8% 49.7% 60.4% 57.4% 46.8% |
|TERMINAL (d) | 4/11 (36%) 8/10 (80%) 5/9 (56%) 5/9 (56%) 6/11 (55%) 4/8 (50%) |
|FIRST INCIDENCE | 275 (T) 192 275 (T) 184 267 184 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.562N P=0.011 * P=0.346 P=0.126 P=0.146 P=0.282 |
|POLY 3 | P=0.459N P=0.005 ** P=0.310 P=0.136 P=0.153 P=0.352 |
|POLY 1.5 | P=0.448N P=0.005 ** P=0.353 P=0.156 P=0.133 P=0.382 |
|POLY 6 | P=0.445N P=0.006 ** P=0.289 P=0.133 P=0.175 P=0.345 |
|LOGISTIC REGRESSION| P=0.477N P=0.008 ** P=0.346 P=0.116 P=0.175 P=0.321 |
|COCH-ARM / FISHERS | P=0.354N P=0.013 * P=0.500 P=0.225 P=0.132 P=0.500 |
|ORDER RESTRICTED | P=0.115 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 8
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 0/15 (0%) 4/15 (27%) 2/15 (13%) 2/15 (13%) 2/15 (13%) |
|POLY-3 RATE (b) | 1/13.22 0/14.31 4/12.30 2/14.97 2/13.91 2/12.70 |
|POLY-3 PERCENT (g) | 7.6% 0.0% 32.5% 13.4% 14.4% 15.7% |
|TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) |
|FIRST INCIDENCE | 197 --- 138 199 138 200 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.406 P=0.471N P=0.135 P=0.560 P=0.509 P=0.481 |
|POLY 3 | P=0.371 P=0.484N P=0.136 P=0.544 P=0.518 P=0.486 |
|POLY 1.5 | P=0.390 P=0.487N P=0.141 P=0.533 P=0.513 P=0.494 |
|POLY 6 | P=0.361 P=0.483N P=0.136 P=0.552 P=0.523 P=0.479 |
|LOGISTIC REGRESSION| P=0.428 P=0.668N P=0.221 P=0.284 P=0.496 P=0.493 |
|COCH-ARM / FISHERS | P=0.426 P=0.500N P=0.165 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.242 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 3/15 (20%) 1/15 (7%) 2/15 (13%) 0/15 (0%) 2/15 (13%) |
|POLY-3 RATE (b) | 1/14.01 3/13.98 1/10.91 2/11.80 0/13.80 2/10.56 |
|POLY-3 PERCENT (g) | 7.1% 21.5% 9.2% 16.9% 0.0% 18.9% |
|TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 1/9 (11%) 0/11 (0%) 0/8 (0%) |
|FIRST INCIDENCE | 109 192 148 97 --- 215 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.579 P=0.289 P=0.727 P=0.469 P=0.514N P=0.411 |
|POLY 3 | P=0.564N P=0.296 P=0.703 P=0.439 P=0.503N P=0.400 |
|POLY 1.5 | P=0.573N P=0.290 P=0.714 P=0.457 P=0.507N P=0.420 |
|POLY 6 | P=0.554N P=0.308 P=0.699 P=0.430 P=0.499N P=0.398 |
|LOGISTIC REGRESSION| P=0.465N P=0.366 P=0.512N P=0.762 P=0.341N P=0.644 |
|COCH-ARM / FISHERS | P=0.564N P=0.299 P=0.759N P=0.500 P=0.500N P=0.500 |
|ORDER RESTRICTED | P=0.351 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/03 EXPERIMENT: 99033 TEST: 01 Page 9
Statistical Analysis of Primary Tumors in Mice(TG.AC 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 |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 10/15 (67%) 9/15 (60%) 7/15 (47%) 8/15 (53%) 11/15 (73%) 11/15 (73%) |
|POLY-3 RATE (b) | 10/14.30 9/15.00 7/12.30 8/15.00 11/14.04 11/14.14 |
|POLY-3 PERCENT (g) | 69.9% 60.0% 56.9% 53.3% 78.3% 77.8% |
|TERMINAL (d) | 5/9 (56%) 6/12 (50%) 3/8 (38%) 5/12 (42%) 8/11 (73%) 7/10 (70%) |
|FIRST INCIDENCE | 76 198 138 199 138 180 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.213 P=0.273N P=0.426N P=0.214N P=0.589N P=0.546 |
|POLY 3 | P=0.146 P=0.432N P=0.387N P=0.296N P=0.468 P=0.480 |
|POLY 1.5 | P=0.148 P=0.456N P=0.351N P=0.318N P=0.459 P=0.479 |
|POLY 6 | P=0.147 P=0.411N P=0.395N P=0.279N P=0.489 P=0.491 |
|LOGISTIC REGRESSION| P=0.153 P=0.566N P=0.251N P=0.416N P=0.501 P=0.500 |
|COCH-ARM / FISHERS | P=0.155 P=0.500N P=0.231N P=0.355N P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.278 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 8/15 (53%) 12/15 (80%) 8/15 (53%) 11/15 (73%) 11/15 (73%) 7/15 (47%) |
|POLY-3 RATE (b) | 8/15.00 12/14.03 8/12.10 11/14.12 11/14.00 7/11.26 |
|POLY-3 PERCENT (g) | 53.3% 85.6% 66.1% 77.9% 78.6% 62.1% |
|TERMINAL (d) | 4/11 (36%) 8/10 (80%) 5/9 (56%) 6/9 (67%) 8/11 (73%) 4/8 (50%) |
|FIRST INCIDENCE | 109 192 148 97 267 184 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.494N P=0.144 P=0.415 P=0.164 P=0.298 P=0.463 |
|POLY 3 | P=0.541 P=0.065 P=0.393 P=0.157 P=0.150 P=0.480 |
|POLY 1.5 | P=0.496N P=0.071 P=0.431 P=0.173 P=0.151 P=0.545 |
|POLY 6 | P=0.509 P=0.064 P=0.385 P=0.151 P=0.150 P=0.456 |
|LOGISTIC REGRESSION| P=0.296N P=0.128 P=0.615 P=0.313 P=0.224 P=0.586N |
|COCH-ARM / FISHERS | P=0.231N P=0.123 P=0.642N P=0.225 P=0.225 P=0.500N |
|ORDER RESTRICTED | P=0.211 (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).