TDMS Study 96006-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE DIMETHYLAMINOPROPYL CHLORIDE, HYDROCHLORIDE DATE: 03/07/05 EXPERIMENT: 96006 TEST: 05 TIME: 07:57:37 TEST TYPE: SUBCHRON 90-DAY CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75408 ROUTE: GAVAGE NTP C#: 96006B PATHOLOGIST: MARTILIK, JOHN CAS: 5407-04-5 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1, REVISION#1 (MALE RATS ONLY) REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 VEHICLE CONTROL INCLUDE 002 6.25 MG/KG INCLUDE 003 12.5 MG/KG INCLUDE 004 25 MG/KG INCLUDE 005 50 MG/KG INCLUDE 006 100 MG/KG INCLUDE 007 VEHICLE CONTROL INCLUDE 008 6.25 MG/KG INCLUDE 009 12.5 MG/KG INCLUDE 010 25 MG/KG INCLUDE 011 50 MG/KG INCLUDE 012 100 MG/KG NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE DIMETHYLAMINOPROPYL CHLORIDE, HYDROCHLORIDE DATE: 03/07/05 EXPERIMENT: 96006 TEST: 05 TIME: 07:57:37 TEST TYPE: SUBCHRON 90-DAY CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75408 ROUTE: GAVAGE NTP C#: 96006B PATHOLOGIST: MARTILIK, JOHN CAS: 5407-04-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF DIMETHYLAMINOPROPYL CHLORIDE, HYDROC =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Nose: Goblet Cell Hypertrophy =============================================================== Date: 03/07/05 EXPERIMENT: 96006 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - DIMETHYLAMINOPROPYL CHLORIDE, HYDROC Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 0/0.00 0/0.00 2/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 20.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) | |FIRST INCIDENCE | --- --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138 (e) (e) (e) (e) P=0.234 | |POLY 3 | (e) (e) (e) (e) (e) P=0.227 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.227 | |POLY 6 | (e) (e) (e) (e) (e) P=0.227 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.234 | |COCH-ARM / FISHERS | P=0.132 (e) (e) (e) (e) P=0.237 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 0/0.00 0/0.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (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: 03/07/05 EXPERIMENT: 96006 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - DIMETHYLAMINOPROPYL CHLORIDE, HYDROC Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Nose: Goblet Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 1/10 (10%) 3/10 (30%) 7/10 (70%) | |POLY-3 RATE (b) | 1/10.00 2/10.00 2/10.00 1/10.00 3/10.00 7/10.00 | |POLY-3 PERCENT (g) | 10.0% 20.0% 20.0% 10.0% 30.0% 70.0% | |TERMINAL (d) | 1/10 (10%) 2/10 (20%) 2/10 (20%) 1/10 (10%) 2/9 (22%) 7/10 (70%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) 93 (T) 79 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500 P=0.500 P=0.766 P=0.272 P=0.013 * | |POLY 3 | P<0.001 ** P=0.500 P=0.500 P=0.760 P=0.292 P=0.003 ** | |POLY 1.5 | P<0.001 ** P=0.500 P=0.500 P=0.760 P=0.292 P=0.003 ** | |POLY 6 | P<0.001 ** P=0.500 P=0.500 P=0.760 P=0.292 P=0.003 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.500 P=0.500 P=0.766 (e) P=0.013 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.500 P=0.763N P=0.291 P=0.010 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Nose: Goblet Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 0/0.00 0/0.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (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: 03/07/05 EXPERIMENT: 96006 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - DIMETHYLAMINOPROPYL CHLORIDE, HYDROC Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/10 (40%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 4/10 (40%) | |POLY-3 RATE (b) | 4/10.00 0/0.00 0/0.00 0/0.00 0/0.00 4/10.00 | |POLY-3 PERCENT (g) | 40.0% 0.0% 0.0% 0.0% 0.0% 40.0% | |TERMINAL (d) | 4/10 (40%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 4/10 (40%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.588 P=1.000N P=1.000N P=1.000N P=1.000N P=0.672 | |POLY 3 | (e) (e) (e) (e) (e) P=0.667 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.667 | |POLY 6 | (e) (e) (e) (e) (e) P=0.667 | |LOGISTIC REGRESSION| P=0.588 (e) (e) (e) (e) P=0.672 | |COCH-ARM / FISHERS | P=0.590 P=1.000 P=1.000 P=1.000 P=1.000 P=0.675N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Focal Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 2/10.00 0/0.00 0/0.00 0/0.00 0/0.00 1/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% 0.0% 10.0% | |TERMINAL (d) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/10 (10%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.380N P=1.000N P=1.000N P=1.000N P=1.000N P=0.500N | |POLY 3 | (e) (e) (e) (e) (e) P=0.500N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.500N | |POLY 6 | (e) (e) (e) (e) (e) P=0.500N | |LOGISTIC REGRESSION| P=0.380N (e) (e) (e) (e) P=0.500N | |COCH-ARM / FISHERS | P=0.377N P=1.000 P=1.000 P=1.000 P=1.000 P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/07/05 EXPERIMENT: 96006 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - DIMETHYLAMINOPROPYL CHLORIDE, HYDROC Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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 6.25 12.5 25 MG/KG 50 MG/KG 100 | | | CONTROL MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 0/0.00 0/0.00 0/0.00 0/0.00 0/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/10 (20%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138N P=1.000N P=1.000N P=1.000N P=1.000N P=0.234N | |POLY 3 | (e) (e) (e) (e) (e) P=0.227N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.227N | |POLY 6 | (e) (e) (e) (e) (e) P=0.227N | |LOGISTIC REGRESSION| P=0.138N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.132N P=1.000 P=1.000 P=1.000 P=1.000 P=0.237N | |ORDER RESTRICTED | (e) (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).