TDMS Study 99033-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF SURVIVAL DATA REPORT: PEIRPT11 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 03 TIME: 11:45:00 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 SURVIVAL DATA REPORT: PEIRPT11 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 03 TIME: 11:45:00 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 TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA MALE MICE FIRST TERMINAL SACRIFICE AT 274 DAYS INDIVIDUAL SURVIVAL TIMES (DAYS) ================================================================================== | DOSE = VEHICLE CONTROL | | ---------------------------- | | | | TOTAL 15 UNCENSORED DEATHS 1 CENSORED DEATHS 0 TERMINAL 14 | | | | UNCENSORED DEATHS | | 63 | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 3125 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 1 CENSORED DEATHS 0 TERMINAL 14 | | | | UNCENSORED DEATHS | | 232 | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 6250 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 0 CENSORED DEATHS 0 TERMINAL 15 | | | | UNCENSORED DEATHS | | NONE | | CENSORED DEATHS | | NONE | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA MALE MICE FIRST TERMINAL SACRIFICE AT 274 DAYS INDIVIDUAL SURVIVAL TIMES (DAYS) ================================================================================== | DOSE = 12500 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 1 CENSORED DEATHS 0 TERMINAL 14 | | | | UNCENSORED DEATHS | | 44 | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 25000 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 1 CENSORED DEATHS 0 TERMINAL 14 | | | | UNCENSORED DEATHS | | 22 | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 50000 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 0 CENSORED DEATHS 0 TERMINAL 15 | | | | UNCENSORED DEATHS | | NONE | | CENSORED DEATHS | | NONE | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA MALE MICE FIRST TERMINAL SACRIFICE AT 274 DAYS ================================================================================== | KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%) | | | |--------------------------------------------------------------------------------| | DOSE TIME (DAYS) | | 28 56 84 112 140 168 196 224 252 274 (A) | | | |--------------------------------------------------------------------------------| | | | |VEHICLE | 100.0 100.0 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 | |CONTROL | | | | | |3125 PPM | 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 93.3 93.3 | | | | | | | |6250 PPM | 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 | | | | | | | |12500 PPM| 100.0 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 | | | | | | | |25000 PPM| 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 93.3 | | | | | | | |50000 PPM| 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 | | | | | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA MALE MICE FIRST TERMINAL SACRIFICE AT 274 DAYS =============================================================================================================================== | SURVIVAL SUMMARY STATISTICS | | | | | |-----------------------------------------------------------------------------------------------------------------------------| | DOSE | | | | VEHICLE 3125 PPM 6250 PPM 12500 PPM 25000 PPM 50000 PPM | | CONTROL | |-----------------------------------------------------------------------------------------------------------------------------| |SURVIVAL AT END OF STUDY| 93.3% 93.3% 100.0% 93.3% 93.3% 100.0% | |(KAPLAN-MEIER) | | | | | |SIGNIFICANCE (B) | P=0.741N P=1.000N P=1.000N P=1.000 P=1.000 P=1.000N | |(LIFE TABLE) | | | | | |MEAN DAY OF | 63.0 232.0 . 44.0 22.0 . | |NATURAL DEATHS (C) | ( . ) ( . ) ( . ) ( . ) ( . ) ( . ) | |(STANDARD ERROR) | | | | | |MEAN LIFE SPAN (D) | 259.9 271.2 274.0 258.7 257.2 274.0 | |(STANDARD ERROR) | (14.1) ( 2.8) ( 0.0) (15.3) (16.8) ( 0.0) | | | | =============================================================================================================================== (A) FIRST TERMINAL SACRIFICE (B) THE FIRST ENTRY IS THE TREND TEST (TARONE, 1975) RESULT. SUBSEQUENT ENTRIES ARE THE RESULTS OF PAIRWISE TESTS (COX,1972). NEGATIVE TRENDS ARE INDICATED BY "N". (C) MEAN OF ALL UNCENSORED DEATHS PRIOR TO TERMINAL SACRIFICE (D) MEAN OF ALL DEATHS (UNCENSORED, CENSORED, TERMINAL SACRIFICE) TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA FEMALE MICE FIRST TERMINAL SACRIFICE AT 275 DAYS INDIVIDUAL SURVIVAL TIMES (DAYS) ================================================================================== | DOSE = VEHICLE CONTROL | | ---------------------------- | | | | TOTAL 15 UNCENSORED DEATHS 2 CENSORED DEATHS 0 TERMINAL 13 | | | | UNCENSORED DEATHS | | 13 219 | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 3125 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 0 CENSORED DEATHS 0 TERMINAL 15 | | | | UNCENSORED DEATHS | | NONE | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 6250 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 2 CENSORED DEATHS 0 TERMINAL 13 | | | | UNCENSORED DEATHS | | 108 216 | | CENSORED DEATHS | | NONE | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA FEMALE MICE FIRST TERMINAL SACRIFICE AT 275 DAYS INDIVIDUAL SURVIVAL TIMES (DAYS) ================================================================================== | DOSE = 12500 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 0 CENSORED DEATHS 0 TERMINAL 15 | | | | UNCENSORED DEATHS | | NONE | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 25000 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 0 CENSORED DEATHS 0 TERMINAL 15 | | | | UNCENSORED DEATHS | | NONE | | CENSORED DEATHS | | NONE | | | |--------------------------------------------------------------------------------| | DOSE = 50000 PPM | | --------------------- | | | | TOTAL 15 UNCENSORED DEATHS 1 CENSORED DEATHS 0 TERMINAL 14 | | | | UNCENSORED DEATHS | | 267 | | CENSORED DEATHS | | NONE | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA FEMALE MICE FIRST TERMINAL SACRIFICE AT 275 DAYS ================================================================================== | KAPLAN-MEIER SURVIVAL PROBABILITY ESTIMATES (%) | | | |--------------------------------------------------------------------------------| | DOSE TIME (DAYS) | | 28 56 84 112 140 168 196 224 252 275 (A) | | | |--------------------------------------------------------------------------------| | | | |VEHICLE | 93.3 93.3 93.3 93.3 93.3 93.3 93.3 86.7 86.7 86.7 | |CONTROL | | | | | |3125 PPM | 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 | | | | | | | |6250 PPM | 100.0 100.0 100.0 93.3 93.3 93.3 93.3 86.7 86.7 86.7 | | | | | | | |12500 PPM| 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 | | | | | | | |25000 PPM| 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 | | | | | | | |50000 PPM| 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 93.3 | | | | | | | ================================================================================== TRANSGENIC MODEL EVALUATION II (ASPARTAME) STATISTICAL ANALYSIS OF SURVIVAL DATA FEMALE MICE FIRST TERMINAL SACRIFICE AT 275 DAYS =============================================================================================================================== | SURVIVAL SUMMARY STATISTICS | | | | | |-----------------------------------------------------------------------------------------------------------------------------| | DOSE | | | | VEHICLE 3125 PPM 6250 PPM 12500 PPM 25000 PPM 50000 PPM | | CONTROL | |-----------------------------------------------------------------------------------------------------------------------------| |SURVIVAL AT END OF STUDY| 86.7% 100.0% 86.7% 100.0% 100.0% 93.3% | |(KAPLAN-MEIER) | | | | | |SIGNIFICANCE (B) | P=0.851N P=0.464N P=1.000 P=0.464N P=0.464N P=0.951N | |(LIFE TABLE) | | | | | |MEAN DAY OF | 116.0 . 162.0 . . 267.0 | |NATURAL DEATHS (C) | ( 103) ( . ) (54.0) ( . ) ( . ) ( . ) | |(STANDARD ERROR) | | | | | |MEAN LIFE SPAN (D) | 253.8 275.0 259.9 275.0 275.0 274.5 | |(STANDARD ERROR) | (17.6) ( 0.0) (11.5) ( 0.0) ( 0.0) ( 0.5) | | | | =============================================================================================================================== (A) FIRST TERMINAL SACRIFICE (B) THE FIRST ENTRY IS THE TREND TEST (TARONE, 1975) RESULT. SUBSEQUENT ENTRIES ARE THE RESULTS OF PAIRWISE TESTS (COX,1972). NEGATIVE TRENDS ARE INDICATED BY "N". (C) MEAN OF ALL UNCENSORED DEATHS PRIOR TO TERMINAL SACRIFICE (D) MEAN OF ALL DEATHS (UNCENSORED, CENSORED, TERMINAL SACRIFICE) TRANSGENIC MODEL EVALUATION II (ASPARTAME) KAPLAN-MEIER SURVIVAL CURVES VEHICLE CONTROL = 1 3125 PPM = 2 6250 PPM = 3 12500 PPM = 4 25000 PPM = 5 50000 PPM = 6 ------------------------------------------------------ SPECIES=MICE SEX=MALE ------------------------------------------------------- Plot of SURVIVAL*WEEK. Symbol is value of DOSE. (NOTE: 9 obs hidden.) P | E | R 100.00 + 1 5 4 1 2 3 C | E | N | T 93.33 + 5 4 1 2 1 | S ---+------------+------------+------------+------------+------------+------------+------------+------------+-- U 0 5 10 15 20 25 30 35 40 R WEEK TRANSGENIC MODEL EVALUATION II (ASPARTAME) KAPLAN-MEIER SURVIVAL CURVES VEHICLE CONTROL = 1 3125 PPM = 2 6250 PPM = 3 12500 PPM = 4 25000 PPM = 5 50000 PPM = 6 ----------------------------------------------------- SPECIES=MICE SEX=FEMALE ------------------------------------------------------ Plot of SURVIVAL*WEEK. Symbol is value of DOSE. (NOTE: 8 obs hidden.) P | E | R 100.00 +1 1 3 6 2 C | E | N | T 93.33 + 1 3 3 1 6 6 | S | U | R 86.67 + 3 1 1 V | I -+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+--+- V 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 A WEEK