TDMS Study 05135-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/15/04 EXPERIMENT: 05135 TEST: 04 TIME: 13:10:41 TEST TYPE: SUBCHRON 90-DAY PAGE: 1 CONT: N01-ES-55105 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C61825 PATHOLOGIST: HAILEY, JAMES R. CAS: 78-79-5 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/15/04 EXPERIMENT: 05135 TEST: 04 TIME: 13:10:41 TEST TYPE: SUBCHRON 90-DAY CONT: N01-ES-55105 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C61825 PATHOLOGIST: HAILEY, JAMES R. CAS: 78-79-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ISOPRENE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Liver Vacuolization Cytoplasmic Nose: Turbinate, Olfactory Epithelium Degeneration Stomach, Forestomach: Epithelium Hyperplasia Testes Atrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Stomach, Forestomach: Epithelium Hyperplasia =============================================================== Date: 10/15/04 EXPERIMENT: 05135 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/2 (0%) 0/10 (0%) 3/9 (33%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/2.00 0/10.00 3/9.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 33.3% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/2 (0%) 0/10 (0%) 3/9 (33%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.093 P<0.001 ** | |POLY 3 | (e) (e) (e) (e) P=0.074 P<0.001 ** | |POLY 1.5 | (e) (e) (e) (e) P=0.074 P<0.001 ** | |POLY 6 | (e) (e) (e) (e) P=0.074 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.093 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.087 P<0.001 ** | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/1 (0%) 0/1 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 0/10.00 0/1.00 0/1.00 0/10.00 0/10.00 1/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 10.0% | |TERMINAL (d) | 0/10 (0%) 0/1 (0%) 0/1 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |FIRST INCIDENCE | --- --- --- --- --- 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.205 (e) (e) (e) (e) P=0.500 | |POLY 3 | P=0.210 (e) (e) (e) (e) P=0.500 | |POLY 1.5 | P=0.210 (e) (e) (e) (e) P=0.500 | |POLY 6 | P=0.210 (e) (e) (e) (e) P=0.500 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.500 | |COCH-ARM / FISHERS | P=0.202 (e) (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.064 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Nose: Turbinate, Olfactory Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 0/0.00 0/0.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 3 | (e) (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | (e) (e) (e) (e) (e) P<0.001 ** | |POLY 6 | (e) (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Nose: Turbinate, Olfactory Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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: 10/15/04 EXPERIMENT: 05135 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/1 (0%) 9/9 (100%) 8/8 (100%) 9/10 (90%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/1.00 9/9.00 8/8.00 9/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% 100.0% 90.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/1 (0%) 9/9 (100%) 8/8 (100%) 9/10 (90%) | |FIRST INCIDENCE | --- --- --- 93 (T) 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007 ** (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.006 ** (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) 9/10 (90%) 10/10 (100%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 10/10.00 9/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% 90.0% 100.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) 9/10 (90%) 10/10 (100%) | |FIRST INCIDENCE | --- --- --- 94 (T) 94 (T) 94 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.002 ** (e) (e) P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Testes | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/1 (0%) 0/10 (0%) 0/9 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/1.00 0/10.00 0/9.00 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%) 0/1 (0%) 0/10 (0%) 0/9 (0%) 2/10 (20%) | |FIRST INCIDENCE | --- --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040 * (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=0.038 * (e) (e) (e) (e) P=0.237 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Testes | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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 | | |=================================================================================================================================| (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).