TDMS Study 05135-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/15/04 EXPERIMENT: 05135 TEST: 03 TIME: 13:06:20 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: 03 TIME: 13:06:20 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 Rats ------------ Organ Morphology ----- ---------- Heart Cardiomyopathy Focal Lung: Alveolar Epithelium Hyperplasia Focal Lung: Alveolus Infiltration Cellular Focal Histiocyte Inflammation Focal Lung: Peribronchial Hyperplasia Focal Lymphoid Lung: Perivascular Hyperplasia Focal Lymphoid Lymph Node, Bronchial Hyperplasia Lymph Node, Mediastinal Hyperplasia Pancreas Accessory Spleen =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Heart Cardiomyopathy Focal Kidney Mineralization Focal Kidney: Bilateral Mineralization Focal Lung: Alveolar Epithelium Hyperplasia Focal Lung: Alveolus Infiltration Cellular Focal Histiocyte Inflammation Focal Lung: Peribronchial Hyperplasia Focal Lymphoid Lung: Perivascular Hyperplasia Focal Lymphoid Lymph Node, Bronchial Hyperplasia =============================================================== Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/10 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) | |POLY-3 RATE (b) | 5/10.00 0/10.00 0/10.00 0/10.00 0/10.00 5/10.00 | |POLY-3 PERCENT (g) | 50.0% 0.0% 0.0% 0.0% 0.0% 50.0% | |TERMINAL (d) | 5/10 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * P=0.022N* P=0.022N* P=0.022N* P=0.022N* P=0.669 | |POLY 3 | P=0.004 ** P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.664 | |POLY 1.5 | P=0.004 ** P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.664 | |POLY 6 | P=0.004 ** P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.664 | |LOGISTIC REGRESSION| P=0.015 * (e) (e) (e) (e) P=0.669 | |COCH-ARM / FISHERS | P=0.015 * P=0.016N* P=0.016N* P=0.016N* P=0.016N* P=0.672N | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.387N P=0.234N P=0.234N P=0.234N P=0.234N P=0.234N | |POLY 3 | P=0.382N P=0.227N P=0.227N P=0.227N P=0.227N P=0.227N | |POLY 1.5 | P=0.382N P=0.227N P=0.227N P=0.227N P=0.227N P=0.227N | |POLY 6 | P=0.382N P=0.227N P=0.227N P=0.227N P=0.227N P=0.227N | |LOGISTIC REGRESSION| P=0.387N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.387N P=0.237N P=0.237N P=0.237N P=0.237N P=0.237N | |ORDER RESTRICTED | P=0.007N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (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) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 8/10 (80%) | |POLY-3 RATE (b) | 9/10.00 0/10.00 0/10.00 0/10.00 1/10.00 8/10.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 10.0% 80.0% | |TERMINAL (d) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 8/10 (80%) | |FIRST INCIDENCE | 93 (T) --- --- --- 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 3 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 1.5 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 6 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) (e) P<0.001N** P=0.500N | |COCH-ARM / FISHERS | P=0.002 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney: Bilateral | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (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) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney: Bilateral | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 8/10 (80%) | |POLY-3 RATE (b) | 9/10.00 0/10.00 0/10.00 0/10.00 1/10.00 8/10.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 10.0% 80.0% | |TERMINAL (d) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 8/10 (80%) | |FIRST INCIDENCE | 93 (T) --- --- --- 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 3 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 1.5 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |POLY 6 | P<0.001 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) (e) P<0.001N** P=0.500N | |COCH-ARM / FISHERS | P=0.002 ** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.500N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 2/10 (20%) 1/10 (10%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 1/10.00 0/10.00 2/10.00 1/10.00 0/10.00 1/10.00 | |POLY-3 PERCENT (g) | 10.0% 0.0% 20.0% 10.0% 0.0% 10.0% | |TERMINAL (d) | 1/10 (10%) 0/10 (0%) 2/10 (20%) 1/10 (10%) 0/10 (0%) 1/10 (10%) | |FIRST INCIDENCE | 93 (T) --- 93 (T) 93 (T) --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.649N P=0.500N P=0.500 P=0.766 P=0.500N P=0.766 | |POLY 3 | P=0.647N P=0.500N P=0.500 P=0.760 P=0.500N P=0.760 | |POLY 1.5 | P=0.647N P=0.500N P=0.500 P=0.760 P=0.500N P=0.760 | |POLY 6 | P=0.647N P=0.500N P=0.500 P=0.760 P=0.500N P=0.760 | |LOGISTIC REGRESSION| P=0.649N (e) P=0.500 P=0.766 (e) P=0.766 | |COCH-ARM / FISHERS | P=0.650N P=0.500N P=0.500 P=0.763N P=0.500N P=0.763N | |ORDER RESTRICTED | P=0.622 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 3/10 (30%) | |POLY-3 RATE (b) | 1/10.00 1/10.00 1/10.00 0/10.00 0/10.00 3/10.00 | |POLY-3 PERCENT (g) | 10.0% 10.0% 10.0% 0.0% 0.0% 30.0% | |TERMINAL (d) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 3/10 (30%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.068 P=0.766 P=0.766 P=0.500N P=0.500N P=0.293 | |POLY 3 | P=0.065 P=0.760 P=0.760 P=0.500N P=0.500N P=0.292 | |POLY 1.5 | P=0.065 P=0.760 P=0.760 P=0.500N P=0.500N P=0.292 | |POLY 6 | P=0.065 P=0.760 P=0.760 P=0.500N P=0.500N P=0.292 | |LOGISTIC REGRESSION| P=0.068 P=0.766 P=0.766 (e) (e) P=0.293 | |COCH-ARM / FISHERS | P=0.066 P=0.763N P=0.763N P=0.500N P=0.500N P=0.291 | |ORDER RESTRICTED | P=0.053 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 10/10.00 10/10.00 10/10.00 10/10.00 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) | |-------------------| | |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) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 10/10.00 10/10.00 10/10.00 10/10.00 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) | |-------------------| | |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: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 9/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.032N* (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.030N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/10 (80%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 8/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 80.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/10 (80%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.045N* (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.044N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Focal Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 9/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.032N* (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.030N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Focal Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/10 (70%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 7/10.00 0/10.00 0/10.00 0/10.00 0/10.00 1/10.00 | |POLY-3 PERCENT (g) | 70.0% 0.0% 0.0% 0.0% 0.0% 10.0% | |TERMINAL (d) | 7/10 (70%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263N P=0.003N** P=0.003N** P=0.003N** P=0.003N** P=0.013N* | |POLY 3 | P=0.178N P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.003N** | |POLY 1.5 | P=0.178N P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.003N** | |POLY 6 | P=0.178N P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.003N** | |LOGISTIC REGRESSION| P=0.263N (e) (e) (e) (e) P=0.013N* | |COCH-ARM / FISHERS | P=0.261N P=0.002N** P=0.002N** P=0.002N** P=0.002N** P=0.010N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 6/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 60.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091N P=0.009N** P=0.009N** P=0.009N** P=0.009N** P=0.009N** | |POLY 3 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.091N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.089N P=0.005N** P=0.005N** P=0.005N** P=0.005N** P=0.005N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/10 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 5/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 50.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 5/10 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.128N P=0.022N* P=0.022N* P=0.022N* P=0.022N* P=0.022N* | |POLY 3 | P=0.071N P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.008N** | |POLY 1.5 | P=0.071N P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.008N** | |POLY 6 | P=0.071N P=0.008N** P=0.008N** P=0.008N** P=0.008N** P=0.008N** | |LOGISTIC REGRESSION| P=0.128N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.126N P=0.016N* P=0.016N* P=0.016N* P=0.016N* P=0.016N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Peribronchial | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 6/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 60.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091N P=0.009N** P=0.009N** P=0.009N** P=0.009N** P=0.009N** | |POLY 3 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.091N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.089N P=0.005N** P=0.005N** P=0.005N** P=0.005N** P=0.005N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Peribronchial | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/10 (40%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 40.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/10 (40%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.182N P=0.051N P=0.051N P=0.051N P=0.051N P=0.051N | |POLY 3 | P=0.140N P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* | |POLY 1.5 | P=0.140N P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* | |POLY 6 | P=0.140N P=0.033N* P=0.033N* P=0.033N* P=0.033N* P=0.033N* | |LOGISTIC REGRESSION| P=0.182N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.180N P=0.043N* P=0.043N* P=0.043N* P=0.043N* P=0.043N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Perivascular | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 9/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 9/10 (90%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.032N* (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.030N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Perivascular | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 6/10.00 0/10.00 0/10.00 0/10.00 0/10.00 0/10.00 | |POLY-3 PERCENT (g) | 60.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/10 (60%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091N P=0.009N** P=0.009N** P=0.009N** P=0.009N** P=0.009N** | |POLY 3 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P=0.027N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.091N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.089N P=0.005N** P=0.005N** P=0.005N** P=0.005N** P=0.005N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 9/9 (100%) 7/7 (100%) 7/7 (100%) 8/8 (100%) 8/9 (89%) | |POLY-3 RATE (b) | 9/10.00 9/9.00 7/7.00 7/7.00 8/8.00 8/9.00 | |POLY-3 PERCENT (g) | 90.0% 100.0% 100.0% 100.0% 100.0% 88.9% | |TERMINAL (d) | 9/10 (90%) 9/9 (100%) 7/7 (100%) 7/7 (100%) 8/8 (100%) 8/9 (89%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.381N P=0.521 P=0.571 P=0.571 P=0.545 P=0.743N | |POLY 3 | P=0.383N P=0.521 P=0.570 P=0.570 P=0.544 P=0.737N | |POLY 1.5 | P=0.383N P=0.521 P=0.570 P=0.570 P=0.544 P=0.737N | |POLY 6 | P=0.383N P=0.521 P=0.570 P=0.570 P=0.544 P=0.737N | |LOGISTIC REGRESSION| P=0.381N P=0.521 P=0.571 P=0.571 P=0.545 P=0.743N | |COCH-ARM / FISHERS | P=0.379N P=0.526 P=0.588 P=0.588 P=0.556 P=0.737N | |ORDER RESTRICTED | P=0.281N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/10 (70%) 4/4 (100%) 10/10 (100%) 7/7 (100%) 7/7 (100%) 7/10 (70%) | |POLY-3 RATE (b) | 7/10.00 4/4.00 10/10.00 7/7.00 7/7.00 7/10.00 | |POLY-3 PERCENT (g) | 70.0% 100.0% 100.0% 100.0% 100.0% 70.0% | |TERMINAL (d) | 7/10 (70%) 4/4 (100%) 10/10 (100%) 7/7 (100%) 7/7 (100%) 7/10 (70%) | |FIRST INCIDENCE | 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.131N P=0.310 P=0.111 P=0.178 P=0.178 P=0.683 | |POLY 3 | P=0.118N P=0.307 P=0.095 P=0.166 P=0.166 P=0.678 | |POLY 1.5 | P=0.118N P=0.307 P=0.095 P=0.166 P=0.166 P=0.678 | |POLY 6 | P=0.118N P=0.307 P=0.095 P=0.166 P=0.166 P=0.678 | |LOGISTIC REGRESSION| P=0.131N P=0.310 P=0.111 P=0.178 P=0.178 P=0.683 | |COCH-ARM / FISHERS | P=0.128N P=0.330 P=0.105 P=0.176 P=0.176 P=0.686N | |ORDER RESTRICTED | P=0.060 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/10 (80%) 0/9 (0%) 0/7 (0%) 0/7 (0%) 0/8 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 8/10.00 0/9.00 0/7.00 0/7.00 0/8.00 0/9.00 | |POLY-3 PERCENT (g) | 80.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/10 (80%) 0/9 (0%) 0/7 (0%) 0/7 (0%) 0/8 (0%) 0/9 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.042N* P<0.001N** P=0.004N** P=0.004N** P=0.002N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.042N* (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.040N* P<0.001N** P=0.002N** P=0.002N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/10 (40%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 0/4.00 0/10.00 0/7.00 0/7.00 0/10.00 | |POLY-3 PERCENT (g) | 40.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/10 (40%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.153N P=0.209N P=0.051N P=0.098N P=0.098N P=0.051N | |POLY 3 | P=0.116N P=0.198N P=0.033N* P=0.079N P=0.079N P=0.033N* | |POLY 1.5 | P=0.116N P=0.198N P=0.033N* P=0.079N P=0.079N P=0.033N* | |POLY 6 | P=0.116N P=0.198N P=0.033N* P=0.079N P=0.079N P=0.033N* | |LOGISTIC REGRESSION| P=0.153N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.151N P=0.210N P=0.043N* P=0.088N P=0.088N P=0.043N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/10 (80%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 9/9 (100%) | |POLY-3 RATE (b) | 8/10.00 0/0.00 0/0.00 0/0.00 0/0.00 9/9.00 | |POLY-3 PERCENT (g) | 80.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 8/10 (80%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 9/9 (100%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.189 P=1.000 P=1.000N P=1.000N P=1.000 P=0.257 | |POLY 3 | (e) (e) (e) (e) (e) P=0.251 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.251 | |POLY 6 | (e) (e) (e) (e) (e) P=0.251 | |LOGISTIC REGRESSION| P=0.189 (e) (e) (e) (e) P=0.257 | |COCH-ARM / FISHERS | P=0.183 P=1.000 P=1.000 P=1.000 P=1.000 P=0.263 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/9 (89%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/10 (80%) | |POLY-3 RATE (b) | 8/9.00 0/0.00 0/0.00 0/0.00 0/0.00 8/10.00 | |POLY-3 PERCENT (g) | 88.9% 0.0% 0.0% 0.0% 0.0% 80.0% | |TERMINAL (d) | 8/9 (89%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/10 (80%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.462N P=1.000N P=1.000N P=1.000 P=1.000 P=0.539N | |POLY 3 | (e) (e) (e) (e) (e) P=0.538N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.538N | |POLY 6 | (e) (e) (e) (e) (e) P=0.538N | |LOGISTIC REGRESSION| P=0.462N (e) (e) (e) (e) P=0.539N | |COCH-ARM / FISHERS | P=0.461N P=1.000 P=1.000 P=1.000 P=1.000 P=0.542N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/10 (90%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/9 (11%) | |POLY-3 RATE (b) | 9/10.00 0/0.00 0/0.00 0/0.00 0/0.00 1/9.00 | |POLY-3 PERCENT (g) | 90.0% 0.0% 0.0% 0.0% 0.0% 11.1% | |TERMINAL (d) | 9/10 (90%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/9 (11%) | |FIRST INCIDENCE | 93 (T) --- --- --- --- 93 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=1.000N P=1.000N P=1.000N P=1.000N P=0.002N** | |POLY 3 | (e) (e) (e) (e) (e) P<0.001N** | |POLY 1.5 | (e) (e) (e) (e) (e) P<0.001N** | |POLY 6 | (e) (e) (e) (e) (e) P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** (e) (e) (e) (e) P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=1.000 P=1.000 P=1.000 P=1.000 P<0.001N** | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/9 (78%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 4/10 (40%) | |POLY-3 RATE (b) | 7/9.00 0/0.00 0/0.00 0/0.00 0/0.00 4/10.00 | |POLY-3 PERCENT (g) | 77.8% 0.0% 0.0% 0.0% 0.0% 40.0% | |TERMINAL (d) | 7/9 (78%) 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=0.095N P=1.000 P=1.000 P=1.000 P=1.000 P=0.121N | |POLY 3 | (e) (e) (e) (e) (e) P=0.110N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.110N | |POLY 6 | (e) (e) (e) (e) (e) P=0.110N | |LOGISTIC REGRESSION| P=0.095N (e) (e) (e) (e) P=0.121N | |COCH-ARM / FISHERS | P=0.089N P=1.000 P=1.000 P=1.000 P=1.000 P=0.115N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Ovary: Periovarian Tissue | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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 | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Ovary: Periovarian Tissue | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/0 (0%) 2/3 (67%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 0/0.00 2/3.00 0/0.00 0/0.00 0/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 66.7% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/10 (20%) 0/0 (0%) 2/3 (67%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |FIRST INCIDENCE | 93 (T) --- 93 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.070N P=1.000 P=0.215 P=1.000 P=1.000 P=0.234N | |POLY 3 | (e) (e) P=0.201 (e) (e) P=0.227N | |POLY 1.5 | (e) (e) P=0.201 (e) (e) P=0.227N | |POLY 6 | (e) (e) P=0.201 (e) (e) P=0.227N | |LOGISTIC REGRESSION| P=0.070N (e) P=0.215 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.066N P=1.000 P=0.203 P=1.000 P=1.000 P=0.237N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 14 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 2/3 (67%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/0.00 0/0.00 1/1.00 2/3.00 0/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% 66.7% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 2/3 (67%) 0/10 (0%) | |FIRST INCIDENCE | --- --- --- 93 (T) 93 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.345N (e) (e) P=0.077 P=0.034 * (e) | |POLY 3 | (e) (e) (e) P=0.091N P=0.003 ** (e) | |POLY 1.5 | (e) (e) (e) P=0.091N P=0.003 ** (e) | |POLY 6 | (e) (e) (e) P=0.091N P=0.003 ** (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.077 P=0.034 * (e) | |COCH-ARM / FISHERS | P=0.341N (e) (e) P=0.091 P=0.038 * (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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) | |=================================================================================================================================| (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).