TDMS Study 99033-02 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03
EXPERIMENT: 99033 TEST: 02 TIME: 11:36:03
TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: C99033
PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0
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FINAL #3/P53 MICE
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE ALL
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03
EXPERIMENT: 99033 TEST: 02 TIME: 11:36:03
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(P53 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.
---------------
Liver
Pituitary Gland
Prostate
Thyroid Gland
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03
EXPERIMENT: 99033 TEST: 02 TIME: 11:36:03
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
----- ----------
All Organs Malignant and Benign Tumors
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
Malignant and Benign Tumors
===============================================================
Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 1
Statistical Analysis of Primary Tumors in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II (ASPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, |
| NOS, or Undifferentiated Cell Type |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/15 (0%) |
|POLY-3 RATE (b) | 0/14.05 0/15.00 2/15.00 0/15.00 0/14.01 0/14.02 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 13.3% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) |
|FIRST INCIDENCE | --- --- 114 --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.389N (e) P=0.247 (e) (e) (e) |
|POLY 3 | P=0.378N (e) P=0.247 (e) (e) (e) |
|POLY 1.5 | P=0.379N (e) P=0.244 (e) (e) (e) |
|POLY 6 | P=0.377N (e) P=0.248 (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.236N (e) P=0.175 (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.381N (e) P=0.241 (e) (e) (e) |
|ORDER RESTRICTED | P=0.380N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, |
| NOS, or Undifferentiated Cell Type |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) |
|POLY-3 RATE (b) | 1/14.00 0/14.05 0/14.23 0/15.00 1/15.00 0/15.00 |
|POLY-3 PERCENT (g) | 7.1% 0.0% 0.0% 0.0% 6.7% 0.0% |
|TERMINAL (d) | 1/14 (7%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) |
|FIRST INCIDENCE | 275 (T) --- --- --- 275 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.570N P=0.500N P=0.500N P=0.486N P=0.749N P=0.486N |
|POLY 3 | P=0.578N P=0.499N P=0.497N P=0.486N P=0.745N P=0.486N |
|POLY 1.5 | P=0.581N P=0.498N P=0.494N P=0.487N P=0.746N P=0.487N |
|POLY 6 | P=0.576N P=0.500N P=0.499N P=0.486N P=0.745N P=0.486N |
|LOGISTIC REGRESSION| P=0.570N (e) (e) (e) P=0.749N (e) |
|COCH-ARM / FISHERS | P=0.586N P=0.500N P=0.500N P=0.500N P=0.759N P=0.500N |
|ORDER RESTRICTED | P=0.176N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 2
Statistical Analysis of Primary Tumors in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II (ASPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 2/15 (13%) |
|POLY-3 RATE (b) | 0/14.05 0/15.00 2/15.00 0/15.00 1/14.01 2/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 13.3% 0.0% 7.1% 13.3% |
|TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 1/14 (7%) 1/14 (7%) |
|FIRST INCIDENCE | --- --- 114 --- 274 (T) 71 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.119 (e) P=0.247 (e) P=0.500 P=0.240 |
|POLY 3 | P=0.123 (e) P=0.247 (e) P=0.499 P=0.247 |
|POLY 1.5 | P=0.122 (e) P=0.244 (e) P=0.498 P=0.244 |
|POLY 6 | P=0.123 (e) P=0.248 (e) P=0.500 P=0.248 |
|LOGISTIC REGRESSION| P=0.184 (e) P=0.175 (e) P=0.500 P=0.233 |
|COCH-ARM / FISHERS | P=0.118 (e) P=0.241 (e) P=0.500 P=0.241 |
|ORDER RESTRICTED | P=0.098 (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) | 3/15 (20%) 0/15 (0%) 2/15 (13%) 2/15 (13%) 1/15 (7%) 1/15 (7%) |
|POLY-3 RATE (b) | 3/14.00 0/14.05 2/14.23 2/15.00 1/15.00 1/15.00 |
|POLY-3 PERCENT (g) | 21.4% 0.0% 14.1% 13.3% 6.7% 6.7% |
|TERMINAL (d) | 3/14 (21%) 0/14 (0%) 2/14 (14%) 2/15 (13%) 1/15 (7%) 1/15 (7%) |
|FIRST INCIDENCE | 275 (T) --- 275 (T) 275 (T) 275 (T) 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.311N P=0.115N P=0.500N P=0.467N P=0.273N P=0.273N |
|POLY 3 | P=0.315N P=0.105N P=0.492N P=0.467N P=0.273N P=0.273N |
|POLY 1.5 | P=0.320N P=0.103N P=0.486N P=0.469N P=0.274N P=0.274N |
|POLY 6 | P=0.313N P=0.105N P=0.498N P=0.467N P=0.273N P=0.273N |
|LOGISTIC REGRESSION| P=0.311N (e) P=0.500N P=0.466N P=0.273N P=0.273N |
|COCH-ARM / FISHERS | P=0.339N P=0.112N P=0.500N P=0.500N P=0.299N P=0.299N |
|ORDER RESTRICTED | P=0.169N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/05/03 EXPERIMENT: 99033 TEST: 02 Page 3
Statistical Analysis of Primary Tumors in Mice(P53 Heterozygous Transgenic) - TRANSGENIC MODEL EVALUATION II (ASPA
Terminal Sacrifice at 40 weeks
|=================================================================================================================================|
| | |
| | Males |
|Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 |
| | CONTROL PPM PPM PPM |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # # # |
|----------- | |
|OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 3/15 (20%) |
|POLY-3 RATE (b) | 0/14.05 0/15.00 2/15.00 0/15.00 1/14.01 3/15.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 13.3% 0.0% 7.1% 20.0% |
|TERMINAL (d) | 0/14 (0%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 1/14 (7%) 2/14 (14%) |
|FIRST INCIDENCE | --- --- 114 --- 274 (T) 71 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.029 * (e) P=0.247 (e) P=0.500 P=0.121 |
|POLY 3 | P=0.027 * (e) P=0.247 (e) P=0.499 P=0.118 |
|POLY 1.5 | P=0.026 * (e) P=0.244 (e) P=0.498 P=0.116 |
|POLY 6 | P=0.027 * (e) P=0.248 (e) P=0.500 P=0.119 |
|LOGISTIC REGRESSION| P=0.041 * (e) P=0.175 (e) P=0.500 P=0.106 |
|COCH-ARM / FISHERS | P=0.027 * (e) P=0.241 (e) P=0.500 P=0.112 |
|ORDER RESTRICTED | P=0.021 * (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) | 4/15 (27%) 0/15 (0%) 2/15 (13%) 2/15 (13%) 1/15 (7%) 1/15 (7%) |
|POLY-3 RATE (b) | 4/14.00 0/14.05 2/14.23 2/15.00 1/15.00 1/15.00 |
|POLY-3 PERCENT (g) | 28.6% 0.0% 14.1% 13.3% 6.7% 6.7% |
|TERMINAL (d) | 4/14 (29%) 0/14 (0%) 2/14 (14%) 2/15 (13%) 1/15 (7%) 1/15 (7%) |
|FIRST INCIDENCE | 275 (T) --- 275 (T) 275 (T) 275 (T) 275 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.214N P=0.056N P=0.326N P=0.293N P=0.147N P=0.147N |
|POLY 3 | P=0.217N P=0.044N* P=0.318N P=0.293N P=0.141N P=0.141N |
|POLY 1.5 | P=0.221N P=0.043N* P=0.311N P=0.295N P=0.142N P=0.142N |
|POLY 6 | P=0.215N P=0.044N* P=0.324N P=0.293N P=0.141N P=0.141N |
|LOGISTIC REGRESSION| P=0.214N (e) P=0.326N P=0.293N P=0.143N P=0.143N |
|COCH-ARM / FISHERS | P=0.238N P=0.050N P=0.326N P=0.326N P=0.165N P=0.165N |
|ORDER RESTRICTED | P=0.047N* (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).