TDMS Study 05135-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/15/04 EXPERIMENT: 05135 TEST: 05 TIME: 13:17:12 TEST TYPE: SIX MONTH EXPOS. PAGE: 1 CONT: N01-ES-55105 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 61825C PATHOLOGIST: HAILEY, JAMES R. PERSING, RONALD 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: 05 TIME: 13:17:12 TEST TYPE: SIX MONTH EXPOS. CONT: N01-ES-55105 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 61825C PATHOLOGIST: HAILEY, JAMES R. PERSING, RONALD CAS: 78-79-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ISOPRENE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Heart Cardiomyopathy Cardiomyopathy Focal Kidney Nephropathy Chronic Kidney: Bilateral Nephropathy Chronic Larynx Infiltration Cellular Mixed Cell Liver Fatty Change Fatty Change Focal Hepatodiaphragmatic Nodule Necrosis Focal Lung Hemorrhage Focal Lung: Alveolar Epithelium Hyperplasia Hyperplasia Focal Lung: Alveolus Hemorrhage Infiltration Cellular Focal Histiocyte Infiltration Cellular Histiocyte Lung: Peribronchial Hyperplasia Focal Lymphoid Hyperplasia Lymphoid Focal Lung: Perivascular Hyperplasia Lymphoid Focal Lymph Node, Bronchial Congestion Hyperplasia Lymph Node, Mandibular Hyperplasia Lymph Node, Mediastinal Congestion Hyperplasia Pigmentation Hemosiderin Mammary Gland Hyperplasia Mesentery Necrosis Pituitary Gland Hyperplasia Preputial Gland Infiltration Cellular Mixed Cell Inflammation Prostate Inflammation Spleen Accessory Spleen Testes: Interstitial Cell Hyperplasia Urinary Bladder Calculus Micro Observation Only =============================================================== Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/5 (80%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/6 (50%) | |POLY-3 RATE (b) | 4/5.00 0/0.00 0/0.00 0/0.00 0/0.00 3/4.26 | |POLY-3 PERCENT (g) | 80.0% 0.0% 0.0% 0.0% 0.0% 70.4% | |INT SACRIFICE 1 (c)| 2/2 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) | |TERMINAL (d) | 2/3 (67%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/4 (75%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.275N P=1.000 P=1.000 P=1.000 P=1.000 P=0.339N | |POLY 3 | (e) (e) (e) (e) (e) P=0.655N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.555N | |POLY 6 | (e) (e) (e) (e) (e) P=0.704N | |LOGISTIC REGRESSION| P=0.253N (e) (e) (e) (e) P=0.322N | |COCH-ARM / FISHERS | P=0.275N P=1.000 P=1.000 P=1.000 P=1.000 P=0.348N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Lymphoid Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/5 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/6 (50%) | |POLY-3 RATE (b) | 0/3.26 0/0.00 0/0.00 0/0.00 0/0.00 3/6.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 50.0% | |INT SACRIFICE 1 (c)| 0/2 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/2 (100%) | |TERMINAL (d) | 0/3 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/4 (25%) | |FIRST INCIDENCE | --- --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.077 (e) (e) (e) (e) P=0.111 | |POLY 3 | (e) (e) (e) (e) (e) P=0.216 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.174 | |POLY 6 | (e) (e) (e) (e) (e) P=0.241 | |LOGISTIC REGRESSION| P=0.055 (e) (e) (e) (e) P=0.085 | |COCH-ARM / FISHERS | P=0.083 (e) (e) (e) (e) P=0.121 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 12/40 (30%) | |POLY-3 RATE (b) | 1/31.31 0/1.31 0/1.40 0/1.31 0/1.31 12/33.92 | |POLY-3 PERCENT (g) | 3.2% 0.0% 0.0% 0.0% 0.0% 35.4% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 3/10 (30%) | |TERMINAL (d) | 1/30 (3%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 9/30 (30%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=1.000N P=1.000N P=1.000N P=1.000N P<0.001 ** | |POLY 3 | P<0.001 ** P=0.856N P=0.846N P=0.856N P=0.856N P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.834N P=0.822N P=0.834N P=0.834N P<0.001 ** | |POLY 6 | P<0.001 ** P=0.866N P=0.857N P=0.866N P=0.866N P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.800N P=0.784N P=0.800N P=0.800N P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 16/40 (40%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 16/37.39 0/1.31 0/1.40 0/1.31 0/1.31 2/32.18 | |POLY-3 PERCENT (g) | 42.8% 0.0% 0.0% 0.0% 0.0% 6.2% | |INT SACRIFICE 1 (c)| 7/10 (70%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 9/30 (30%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/30 (3%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004N** P=0.003N** P=0.003N** P=0.003N** P=0.003N** P<0.001N** | |POLY 3 | P<0.001N** P=0.487N P=0.478N P=0.487N P=0.487N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.244N P=0.227N P=0.244N P=0.244N P<0.001N** | |POLY 6 | P<0.001N** P=0.622N P=0.617N P=0.622N P=0.622N P<0.001N** | |LOGISTIC REGRESSION| P=0.004N** P=0.002N** P=0.002N** P=0.002N** P=0.002N** P<0.001N** | |COCH-ARM / FISHERS | P=0.008N** P=0.013N* P=0.009N** P=0.013N* P=0.013N* P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/40 (10%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 6/40 (15%) | |POLY-3 RATE (b) | 4/31.31 0/1.31 0/1.40 0/1.31 0/1.31 6/31.31 | |POLY-3 PERCENT (g) | 12.8% 0.0% 0.0% 0.0% 0.0% 19.2% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 4/30 (13%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 6/30 (20%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.326 P=1.000 P=1.000 P=1.000 P=1.000 P=0.366 | |POLY 3 | P=0.257 P=0.661N P=0.651N P=0.661N P=0.661N P=0.366 | |POLY 1.5 | P=0.203 P=0.556N P=0.540N P=0.556N P=0.556N P=0.366 | |POLY 6 | P=0.266 P=0.714N P=0.706N P=0.714N P=0.714N P=0.366 | |LOGISTIC REGRESSION| P=0.326 (e) (e) (e) (e) P=0.366 | |COCH-ARM / FISHERS | P=0.075 P=0.397N P=0.366N P=0.397N P=0.397N P=0.369 | |ORDER RESTRICTED | P=0.100 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/40 (57%) 0/10 (0%) 1/12 (8%) 2/12 (17%) 6/16 (38%) 29/40 (73%) | |POLY-3 RATE (b) | 23/31.31 0/1.31 1/2.40 2/3.31 6/7.31 29/31.31 | |POLY-3 PERCENT (g) | 73.5% 0.0% 41.7% 60.4% 82.1% 92.6% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 23/30 (77%) 0/0 (0%) 1/1 (100%) 2/2 (100%) 6/6 (100%) 29/30 (97%) | |FIRST INCIDENCE | 366 (T) --- 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.031 * P=1.000 P=0.744 P=0.543 P=0.229 P=0.030 * | |POLY 3 | P=0.004 ** P=0.341N P=0.424N P=0.540N P=0.497 P=0.029 * | |POLY 1.5 | P<0.001 ** P=0.052N P=0.086N P=0.174N P=0.515N P=0.046 * | |POLY 6 | P=0.006 ** P=0.637N P=0.643 P=0.566 P=0.304 P=0.026 * | |LOGISTIC REGRESSION| P=0.030 * (e) P=0.744 P=0.543 P=0.229 P=0.030 * | |COCH-ARM / FISHERS | P<0.001 ** P<0.001N** P=0.003N** P=0.014N* P=0.145N P=0.120 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Kidney: Bilateral | | Nephropathy Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/40 (57%) 0/10 (0%) 1/12 (8%) 1/12 (8%) 6/16 (38%) 29/40 (73%) | |POLY-3 RATE (b) | 23/31.31 0/1.31 1/2.40 1/3.31 6/7.31 29/31.31 | |POLY-3 PERCENT (g) | 73.5% 0.0% 41.7% 30.2% 82.1% 92.6% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 23/30 (77%) 0/0 (0%) 1/1 (100%) 1/2 (50%) 6/6 (100%) 29/30 (97%) | |FIRST INCIDENCE | 366 (T) --- 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.020 * P=1.000 P=0.744 P=0.500N P=0.229 P=0.030 * | |POLY 3 | P=0.003 ** P=0.341N P=0.424N P=0.237N P=0.497 P=0.029 * | |POLY 1.5 | P<0.001 ** P=0.052N P=0.086N P=0.047N* P=0.515N P=0.046 * | |POLY 6 | P=0.006 ** P=0.637N P=0.643 P=0.460N P=0.304 P=0.026 * | |LOGISTIC REGRESSION| P=0.020 * (e) P=0.744 P=0.500N P=0.229 P=0.030 * | |COCH-ARM / FISHERS | P<0.001 ** P<0.001N** P=0.003N** P=0.003N** P=0.145N P=0.120 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Larynx | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 3/40 (8%) | |POLY-3 RATE (b) | 1/31.31 0/1.31 0/1.31 0/1.31 0/1.31 3/31.31 | |POLY-3 PERCENT (g) | 3.2% 0.0% 0.0% 0.0% 0.0% 9.6% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/30 (3%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/30 (10%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.250 P=1.000 P=1.000 P=1.000N P=1.000 P=0.304 | |POLY 3 | P=0.175 P=0.856N P=0.856N P=0.856N P=0.856N P=0.303 | |POLY 1.5 | P=0.158 P=0.834N P=0.834N P=0.834N P=0.834N P=0.304 | |POLY 6 | P=0.176 P=0.866N P=0.866N P=0.866N P=0.866N P=0.303 | |LOGISTIC REGRESSION| P=0.250 (e) (e) (e) (e) P=0.304 | |COCH-ARM / FISHERS | P=0.094 P=0.800N P=0.800N P=0.800N P=0.800N P=0.308 | |ORDER RESTRICTED | P=0.041 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/15 (0%) 3/22 (14%) 4/15 (27%) 0/17 (0%) 0/40 (0%) | |POLY-3 RATE (b) | 1/31.31 0/6.31 3/12.40 4/6.31 0/8.31 0/31.31 | |POLY-3 PERCENT (g) | 3.2% 0.0% 24.2% 63.4% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/30 (3%) 0/5 (0%) 3/11 (27%) 4/5 (80%) 0/7 (0%) 0/30 (0%) | |FIRST INCIDENCE | 366 (T) --- 366 (T) 366 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040N* P=0.846N P=0.047 * P<0.001 ** P=0.786N P=0.500N | |POLY 3 | P=0.062N P=0.765N P=0.065 P<0.001 ** P=0.733N P=0.500N | |POLY 1.5 | P=0.057N P=0.744N P=0.080 P=0.002 ** P=0.713N P=0.500N | |POLY 6 | P=0.068N P=0.777N P=0.058 P<0.001 ** P=0.743N P=0.500N | |LOGISTIC REGRESSION| P=0.040N* (e) P=0.047 * P<0.001 ** (e) (e) | |COCH-ARM / FISHERS | P=0.069N P=0.727N P=0.124 P=0.017 * P=0.702N P=0.500N | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/40 (0%) 0/15 (0%) 2/22 (9%) 1/15 (7%) 1/17 (6%) 0/40 (0%) | |POLY-3 RATE (b) | 0/31.31 0/6.31 2/12.40 1/6.31 1/8.31 0/31.31 | |POLY-3 PERCENT (g) | 0.0% 0.0% 16.1% 15.8% 12.0% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/30 (0%) 0/5 (0%) 2/11 (18%) 1/5 (20%) 1/7 (14%) 0/30 (0%) | |FIRST INCIDENCE | --- --- 366 (T) 366 (T) 366 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.223N (e) P=0.060 P=0.154 P=0.214 (e) | |POLY 3 | P=0.289N (e) P=0.076 P=0.227 P=0.262 (e) | |POLY 1.5 | P=0.282N (e) P=0.087 P=0.250 P=0.283 (e) | |POLY 6 | P=0.298N (e) P=0.071 P=0.215 P=0.251 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.060 P=0.154 P=0.214 (e) | |COCH-ARM / FISHERS | P=0.290N (e) P=0.122 P=0.273 P=0.298 (e) | |ORDER RESTRICTED | P=0.039 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/40 (13%) 9/15 (60%) 8/22 (36%) 4/15 (27%) 8/17 (47%) 6/40 (15%) | |POLY-3 RATE (b) | 5/33.92 9/9.79 8/13.27 4/8.92 8/10.92 6/31.31 | |POLY-3 PERCENT (g) | 14.7% 92.0% 60.3% 44.9% 73.3% 19.2% | |INT SACRIFICE 1 (c)| 3/10 (30%) 4/10 (40%) 1/10 (10%) 3/10 (30%) 3/10 (30%) 0/10 (0%) | |TERMINAL (d) | 2/30 (7%) 5/5 (100%) 7/11 (64%) 1/5 (20%) 5/7 (71%) 6/30 (20%) | |FIRST INCIDENCE | 186 (I) 186 (I) 186 (I) 186 (I) 186 (I) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059N P=0.002 ** P=0.020 * P=0.476 P=0.012 * P=0.500 | |POLY 3 | P=0.053N P<0.001 ** P=0.003 ** P=0.084 P<0.001 ** P=0.443 | |POLY 1.5 | P=0.054N P<0.001 ** P=0.006 ** P=0.112 P<0.001 ** P=0.460 | |POLY 6 | P=0.056N P<0.001 ** P=0.002 ** P=0.071 P<0.001 ** P=0.433 | |LOGISTIC REGRESSION| P=0.060N P=0.002 ** P=0.021 * P=0.476 P=0.011 * P=0.500 | |COCH-ARM / FISHERS | P=0.081N P<0.001 ** P=0.032 * P=0.193 P=0.008 ** P=0.500 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/15 (0%) 0/22 (0%) 0/15 (0%) 0/17 (0%) 1/40 (3%) | |POLY-3 RATE (b) | 2/31.31 0/6.31 0/12.40 0/6.31 0/8.31 1/32.18 | |POLY-3 PERCENT (g) | 6.4% 0.0% 0.0% 0.0% 0.0% 3.1% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 2/30 (7%) 0/5 (0%) 0/11 (0%) 0/5 (0%) 0/7 (0%) 0/30 (0%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.677 P=0.670N P=0.476N P=0.670N P=0.588N P=0.500N | |POLY 3 | P=0.560N P=0.602N P=0.460N P=0.602N P=0.549N P=0.490N | |POLY 1.5 | P=0.612N P=0.558N P=0.432N P=0.558N P=0.512N P=0.493N | |POLY 6 | P=0.529N P=0.626N P=0.476N P=0.626N P=0.570N P=0.489N | |LOGISTIC REGRESSION| P=0.677 (e) (e) (e) (e) P=0.500N | |COCH-ARM / FISHERS | P=0.662 P=0.525N P=0.412N P=0.525N P=0.489N P=0.500N | |ORDER RESTRICTED | P=0.095N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/15 (0%) 3/22 (14%) 0/15 (0%) 0/17 (0%) 4/40 (10%) | |POLY-3 RATE (b) | 1/31.31 0/6.31 3/12.40 0/6.31 0/8.31 4/31.31 | |POLY-3 PERCENT (g) | 3.2% 0.0% 24.2% 0.0% 0.0% 12.8% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/30 (3%) 0/5 (0%) 3/11 (27%) 0/5 (0%) 0/7 (0%) 4/30 (13%) | |FIRST INCIDENCE | 366 (T) --- 366 (T) --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.274 P=0.846N P=0.047 * P=0.846N P=0.786N P=0.177 | |POLY 3 | P=0.209 P=0.765N P=0.065 P=0.765N P=0.733N P=0.175 | |POLY 1.5 | P=0.190 P=0.744N P=0.080 P=0.744N P=0.713N P=0.176 | |POLY 6 | P=0.219 P=0.777N P=0.058 P=0.777N P=0.743N P=0.175 | |LOGISTIC REGRESSION| P=0.274 (e) P=0.047 * (e) (e) P=0.177 | |COCH-ARM / FISHERS | P=0.153 P=0.727N P=0.124 P=0.727N P=0.702N P=0.179 | |ORDER RESTRICTED | P=0.029 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/40 (13%) 10/40 (25%) 11/40 (28%) 10/40 (25%) 10/40 (25%) 5/40 (13%) | |POLY-3 RATE (b) | 5/31.31 10/40.00 11/39.09 10/40.00 10/40.00 5/32.18 | |POLY-3 PERCENT (g) | 16.0% 25.0% 28.1% 25.0% 25.0% 15.5% | |INT SACRIFICE 1 (c)| 0/10 (0%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 1/10 (10%) | |TERMINAL (d) | 5/30 (17%) 0/30 (0%) 1/29 (3%) 0/30 (0%) 0/30 (0%) 4/30 (13%) | |FIRST INCIDENCE | 366 (T) 186 (I) 186 (I) 186 (I) 186 (I) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.074N P=0.102 P=0.060 P=0.102 P=0.102 P=0.632 | |POLY 3 | P=0.224N P=0.267 P=0.181 P=0.267 P=0.267 P=0.616N | |POLY 1.5 | P=0.196N P=0.218 P=0.144 P=0.218 P=0.218 P=0.621N | |POLY 6 | P=0.240N P=0.293 P=0.203 P=0.293 P=0.293 P=0.613N | |LOGISTIC REGRESSION| P=0.089N P=0.098 P=0.081 P=0.098 P=0.098 P=0.633N | |COCH-ARM / FISHERS | P=0.139N P=0.126 P=0.081 P=0.126 P=0.126 P=0.631N | |ORDER RESTRICTED | P=0.412N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 35/40 (88%) 30/40 (75%) 26/40 (65%) 24/40 (60%) 22/40 (55%) 35/40 (88%) | |POLY-3 RATE (b) | 35/40.00 30/31.31 26/30.40 24/31.31 22/31.31 35/39.13 | |POLY-3 PERCENT (g) | 87.5% 95.8% 85.5% 76.7% 70.3% 89.4% | |INT SACRIFICE 1 (c)| 10/10 (100%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 9/10 (90%) | |TERMINAL (d) | 25/30 (83%) 30/30 (100%) 26/29 (90%) 24/30 (80%) 22/30 (73%) 26/30 (87%) | |FIRST INCIDENCE | 186 (I) 366 (T) 366 (T) 366 (T) 366 (T) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.067 P=0.102N P=0.021N* P=0.004N** P<0.001N** P=0.632 | |POLY 3 | P=0.474 P=0.193 P=0.546N P=0.182N P=0.061N P=0.532 | |POLY 1.5 | P=0.284 P=0.560 P=0.236N P=0.062N P=0.017N* P=0.560 | |POLY 6 | P=0.583 P=0.075 P=0.567 P=0.288N P=0.110N P=0.518 | |LOGISTIC REGRESSION| P=0.063 P=0.098N P=0.015N* P=0.004N** P<0.001N** P=0.633 | |COCH-ARM / FISHERS | P=0.088 P=0.126N P=0.017N* P=0.005N** P<0.001N** P=0.631N | |ORDER RESTRICTED | P=0.075N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/40 (8%) 0/40 (0%) 0/40 (0%) 1/40 (3%) 0/40 (0%) 1/40 (3%) | |POLY-3 RATE (b) | 3/31.31 0/31.31 0/30.40 1/31.31 0/31.31 1/32.18 | |POLY-3 PERCENT (g) | 9.6% 0.0% 0.0% 3.2% 0.0% 3.1% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 3/30 (10%) 0/30 (0%) 0/29 (0%) 1/30 (3%) 0/30 (0%) 0/30 (0%) | |FIRST INCIDENCE | 366 (T) --- --- 366 (T) --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.612N P=0.120N P=0.126N P=0.304N P=0.120N P=0.306N | |POLY 3 | P=0.607N P=0.116N P=0.122N P=0.303N P=0.116N P=0.294N | |POLY 1.5 | P=0.610N P=0.117N P=0.120N P=0.304N P=0.117N P=0.297N | |POLY 6 | P=0.605N P=0.116N P=0.122N P=0.303N P=0.116N P=0.292N | |LOGISTIC REGRESSION| P=0.614N (e) (e) P=0.304N (e) P=0.304N | |COCH-ARM / FISHERS | P=0.615N P=0.120N P=0.120N P=0.308N P=0.120N P=0.308N | |ORDER RESTRICTED | P=0.026N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 15/40 (38%) 13/40 (33%) 11/40 (28%) 12/40 (30%) 5/40 (13%) | |POLY-3 RATE (b) | 2/31.31 15/31.31 13/30.40 11/31.31 12/31.31 5/31.31 | |POLY-3 PERCENT (g) | 6.4% 47.9% 42.8% 35.1% 38.3% 16.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/30 (7%) 15/30 (50%) 13/29 (45%) 11/30 (37%) 12/30 (40%) 5/30 (17%) | |FIRST INCIDENCE | 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.066N P<0.001 ** P<0.001 ** P=0.006 ** P=0.003 ** P=0.213 | |POLY 3 | P=0.061N P<0.001 ** P<0.001 ** P=0.005 ** P=0.002 ** P=0.212 | |POLY 1.5 | P=0.064N P<0.001 ** P<0.001 ** P=0.005 ** P=0.002 ** P=0.212 | |POLY 6 | P=0.060N P<0.001 ** P<0.001 ** P=0.005 ** P=0.002 ** P=0.211 | |LOGISTIC REGRESSION| P=0.066N P<0.001 ** P<0.001 ** P=0.006 ** P=0.003 ** P=0.213 | |COCH-ARM / FISHERS | P=0.081N P<0.001 ** P=0.002 ** P=0.006 ** P=0.003 ** P=0.216 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/40 (0%) 0/40 (0%) 0/40 (0%) 1/40 (3%) 3/40 (8%) | |POLY-3 RATE (b) | 2/31.31 0/31.31 0/30.40 0/31.31 1/31.31 3/32.18 | |POLY-3 PERCENT (g) | 6.4% 0.0% 0.0% 0.0% 3.2% 9.3% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 2/30 (7%) 0/30 (0%) 0/29 (0%) 0/30 (0%) 1/30 (3%) 2/30 (7%) | |FIRST INCIDENCE | 366 (T) --- --- --- 366 (T) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040 * P=0.238N P=0.245N P=0.238N P=0.500N P=0.500 | |POLY 3 | P=0.041 * P=0.236N P=0.243N P=0.236N P=0.500N P=0.513 | |POLY 1.5 | P=0.040 * P=0.236N P=0.241N P=0.236N P=0.500N P=0.509 | |POLY 6 | P=0.041 * P=0.236N P=0.243N P=0.236N P=0.500N P=0.515 | |LOGISTIC REGRESSION| P=0.039 * (e) (e) (e) P=0.500N P=0.500 | |COCH-ARM / FISHERS | P=0.039 * P=0.247N P=0.247N P=0.247N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.058 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Focal Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/40 (10%) 17/40 (43%) 19/40 (48%) 17/40 (43%) 16/40 (40%) 19/40 (48%) | |POLY-3 RATE (b) | 4/33.05 17/31.31 19/30.40 17/31.31 16/31.31 19/31.31 | |POLY-3 PERCENT (g) | 12.1% 54.3% 62.5% 54.3% 51.1% 60.7% | |INT SACRIFICE 1 (c)| 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/30 (7%) 17/30 (57%) 19/29 (66%) 17/30 (57%) 16/30 (53%) 19/30 (63%) | |FIRST INCIDENCE | 186 (I) 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.063 P<0.001 ** P<0.001 ** P<0.001 ** P=0.002 ** P<0.001 ** | |POLY 3 | P=0.037 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.044 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.034 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.062 P<0.001 ** P<0.001 ** P<0.001 ** P=0.002 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.076 P<0.001 ** P<0.001 ** P<0.001 ** P=0.002 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/40 (0%) 0/40 (0%) 1/40 (3%) 0/40 (0%) 0/40 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 0/31.31 0/31.31 1/31.27 0/31.31 0/31.31 2/32.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 3.2% 0.0% 0.0% 6.2% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/30 (0%) 0/30 (0%) 0/29 (0%) 0/30 (0%) 0/30 (0%) 1/30 (3%) | |FIRST INCIDENCE | --- --- 186 (I) --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.058 (e) P=0.500 (e) (e) P=0.240 | |POLY 3 | P=0.059 (e) P=0.500 (e) (e) P=0.242 | |POLY 1.5 | P=0.059 (e) P=0.500 (e) (e) P=0.240 | |POLY 6 | P=0.059 (e) P=0.500 (e) (e) P=0.243 | |LOGISTIC REGRESSION| P=0.055 (e) P=0.536 (e) (e) P=0.236 | |COCH-ARM / FISHERS | P=0.058 (e) P=0.500 (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Peribronchial | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/40 (0%) 2/40 (5%) 3/40 (8%) 0/40 (0%) 0/40 (0%) 4/40 (10%) | |POLY-3 RATE (b) | 0/31.31 2/31.31 3/30.40 0/31.31 0/31.31 4/33.92 | |POLY-3 PERCENT (g) | 0.0% 6.4% 9.9% 0.0% 0.0% 11.8% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 3/10 (30%) | |TERMINAL (d) | 0/30 (0%) 2/30 (7%) 3/29 (10%) 0/30 (0%) 0/30 (0%) 1/30 (3%) | |FIRST INCIDENCE | --- 366 (T) 366 (T) --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.066 P=0.238 P=0.114 (e) (e) P=0.059 | |POLY 3 | P=0.070 P=0.236 P=0.111 (e) (e) P=0.069 | |POLY 1.5 | P=0.067 P=0.236 P=0.113 (e) (e) P=0.066 | |POLY 6 | P=0.071 P=0.236 P=0.110 (e) (e) P=0.071 | |LOGISTIC REGRESSION| P=0.064 P=0.238 P=0.114 (e) (e) P=0.055 | |COCH-ARM / FISHERS | P=0.064 P=0.247 P=0.120 (e) (e) P=0.058 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Peribronchial | | Hyperplasia Lymphoid Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/40 (13%) 8/40 (20%) 7/40 (18%) 7/40 (18%) 4/40 (10%) 1/40 (3%) | |POLY-3 RATE (b) | 5/35.66 8/31.31 7/30.40 7/31.31 4/31.31 1/31.31 | |POLY-3 PERCENT (g) | 14.0% 25.6% 23.0% 22.4% 12.8% 3.2% | |INT SACRIFICE 1 (c)| 5/10 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/30 (0%) 8/30 (27%) 7/29 (24%) 7/30 (23%) 4/30 (13%) 1/30 (3%) | |FIRST INCIDENCE | 186 (I) 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013N* P=0.273 P=0.363 P=0.377 P=0.500N P=0.089N | |POLY 3 | P=0.015N* P=0.191 P=0.268 P=0.287 P=0.582N P=0.132N | |POLY 1.5 | P=0.014N* P=0.213 P=0.299 P=0.313 P=0.557N P=0.121N | |POLY 6 | P=0.016N* P=0.179 P=0.253 P=0.273 P=0.595N P=0.138N | |LOGISTIC REGRESSION| P=0.012N* P=0.270 P=0.392 P=0.376 P=0.500N P=0.084N | |COCH-ARM / FISHERS | P=0.013N* P=0.273 P=0.378 P=0.378 P=0.500N P=0.100N | |ORDER RESTRICTED | P=0.032N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Perivascular | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 1/40 (3%) 0/40 (0%) 2/40 (5%) 2/40 (5%) 2/40 (5%) | |POLY-3 RATE (b) | 1/32.18 1/32.18 0/30.40 2/31.31 2/31.31 2/32.18 | |POLY-3 PERCENT (g) | 3.1% 3.1% 0.0% 6.4% 6.4% 6.2% | |INT SACRIFICE 1 (c)| 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/30 (0%) 0/30 (0%) 0/29 (0%) 2/30 (7%) 2/30 (7%) 1/30 (3%) | |FIRST INCIDENCE | 186 (I) 186 (I) --- 366 (T) 366 (T) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.290 P=0.766 P=0.500N P=0.500 P=0.500 P=0.500 | |POLY 3 | P=0.298 P=0.761 P=0.511N P=0.490 P=0.490 P=0.500 | |POLY 1.5 | P=0.295 P=0.761 P=0.508N P=0.493 P=0.493 P=0.500 | |POLY 6 | P=0.300 P=0.761 P=0.513N P=0.489 P=0.489 P=0.500 | |LOGISTIC REGRESSION| P=0.285 (e) P=0.464N P=0.500 P=0.500 P=0.500 | |COCH-ARM / FISHERS | P=0.287 P=0.753N P=0.500N P=0.500 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.361 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lung: Perivascular | | Hyperplasia Lymphoid Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/40 (38%) 23/40 (57%) 25/40 (63%) 20/40 (50%) 17/40 (43%) 23/40 (57%) | |POLY-3 RATE (b) | 15/35.66 23/32.18 25/32.14 20/32.18 17/33.92 23/31.31 | |POLY-3 PERCENT (g) | 42.1% 71.5% 77.8% 62.2% 50.1% 73.5% | |INT SACRIFICE 1 (c)| 5/10 (50%) 1/10 (10%) 2/10 (20%) 1/10 (10%) 3/10 (30%) 0/10 (0%) | |TERMINAL (d) | 10/30 (33%) 22/30 (73%) 23/29 (79%) 19/30 (63%) 14/30 (47%) 23/30 (77%) | |FIRST INCIDENCE | 186 (I) 186 (I) 186 (I) 186 (I) 186 (I) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.342 P=0.057 P=0.015 * P=0.183 P=0.411 P=0.054 | |POLY 3 | P=0.176 P=0.011 * P=0.002 ** P=0.076 P=0.333 P=0.007 ** | |POLY 1.5 | P=0.220 P=0.019 * P=0.004 ** P=0.101 P=0.355 P=0.014 * | |POLY 6 | P=0.156 P=0.009 ** P<0.001 ** P=0.066 P=0.322 P=0.005 ** | |LOGISTIC REGRESSION| P=0.337 P=0.055 P=0.017 * P=0.181 P=0.410 P=0.052 | |COCH-ARM / FISHERS | P=0.335 P=0.058 P=0.022 * P=0.184 P=0.410 P=0.058 | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 17/32 (53%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/11 (0%) 19/37 (51%) | |POLY-3 RATE (b) | 17/32.00 0/1.31 0/1.40 0/1.31 0/2.31 19/35.26 | |POLY-3 PERCENT (g) | 53.1% 0.0% 0.0% 0.0% 0.0% 53.9% | |INT SACRIFICE 1 (c)| 9/9 (100%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 8/10 (80%) | |TERMINAL (d) | 8/23 (35%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 11/27 (41%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.022 * P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.563N | |POLY 3 | P=0.488 P=0.450N P=0.440N P=0.450N P=0.321N P=0.572 | |POLY 1.5 | P=0.307 P=0.171N P=0.154N P=0.171N P=0.107N P=0.594 | |POLY 6 | P=0.513 P=0.615N P=0.610N P=0.615N P=0.472N P=0.561 | |LOGISTIC REGRESSION| P=0.020 * P<0.001N** P<0.001N** P<0.001N** P<0.001N** P=0.563N | |COCH-ARM / FISHERS | P=0.011 * P=0.002N** P<0.001N** P=0.002N** P<0.001N** P=0.538N | |ORDER RESTRICTED | P=0.157 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Bronchial | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/32 (3%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 1/11 (9%) 6/37 (16%) | |POLY-3 RATE (b) | 1/25.05 0/1.31 0/1.40 0/1.31 1/2.31 6/28.31 | |POLY-3 PERCENT (g) | 4.0% 0.0% 0.0% 0.0% 43.2% 21.2% | |INT SACRIFICE 1 (c)| 1/9 (11.1%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/23 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 6/27 (22%) | |FIRST INCIDENCE | 186 (I) --- --- --- 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.061 P=0.479N P=0.479N P=0.479N P=0.550 P=0.084 | |POLY 3 | P=0.025 * P=0.832N P=0.823N P=0.832N P=0.302 P=0.070 | |POLY 1.5 | P=0.021 * P=0.805N P=0.793N P=0.805N P=0.369 P=0.073 | |POLY 6 | P=0.025 * P=0.845N P=0.836N P=0.845N P=0.267 P=0.069 | |LOGISTIC REGRESSION| P=0.059 (e) P=0.450N (e) P=0.552 P=0.082 | |COCH-ARM / FISHERS | P=0.008 ** P=0.762N P=0.744N P=0.762N P=0.451 P=0.078 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/35 (3%) 0/10 (0%) 0/12 (0%) 1/11 (9%) 0/10 (0%) 3/40 (8%) | |POLY-3 RATE (b) | 1/27.18 0/1.31 0/2.40 1/3.18 0/1.31 3/33.05 | |POLY-3 PERCENT (g) | 3.7% 0.0% 0.0% 31.4% 0.0% 9.1% | |INT SACRIFICE 1 (c)| 0/9 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 2/10 (20%) | |TERMINAL (d) | 1/26 (4%) 0/0 (0%) 0/1 (0%) 0/1 (0%) 0/0 (0%) 1/30 (3%) | |FIRST INCIDENCE | 366 (T) --- --- 186 (I) --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.145 P=1.000 P=0.993N P=0.547 P=1.000 P=0.351 | |POLY 3 | P=0.302 P=0.842N P=0.813N P=0.317 P=0.842N P=0.377 | |POLY 1.5 | P=0.287 P=0.816N P=0.785N P=0.372 P=0.816N P=0.369 | |POLY 6 | P=0.309 P=0.853N P=0.826N P=0.288 P=0.853N P=0.381 | |LOGISTIC REGRESSION| P=0.140 (e) (e) P=0.548 (e) P=0.348 | |COCH-ARM / FISHERS | P=0.192 P=0.778N P=0.745N P=0.425 P=0.778N P=0.360 | |ORDER RESTRICTED | P=0.058 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/35 (23%) 0/10 (0%) 1/12 (8%) 0/11 (0%) 0/10 (0%) 5/40 (13%) | |POLY-3 RATE (b) | 8/28.05 0/1.31 1/2.40 0/2.31 0/1.31 5/31.31 | |POLY-3 PERCENT (g) | 28.5% 0.0% 41.7% 0.0% 0.0% 16.0% | |INT SACRIFICE 1 (c)| 1/9 (11.1%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 7/26 (27%) 0/0 (0%) 1/1 (100%) 0/1 (0%) 0/0 (0%) 5/30 (17%) | |FIRST INCIDENCE | 186 (I) --- 366 (T) --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.160N P=0.479N P=0.683 P=0.334N P=0.479N P=0.185N | |POLY 3 | P=0.121N P=0.552N P=0.570 P=0.461N P=0.552N P=0.196N | |POLY 1.5 | P=0.194N P=0.365N P=0.578N P=0.298N P=0.365N P=0.194N | |POLY 6 | P=0.111N P=0.654N P=0.459 P=0.558N P=0.654N P=0.199N | |LOGISTIC REGRESSION| P=0.158N P=0.478N P=0.697 P=0.330N P=0.478N P=0.183N | |COCH-ARM / FISHERS | P=0.517N P=0.109N P=0.259N P=0.090N P=0.109N P=0.190N | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 20/35 (57%) 3/15 (20%) 1/12 (8%) 0/11 (0%) 1/10 (10%) 17/30 (57%) | |POLY-3 RATE (b) | 20/35.00 3/7.18 1/3.27 0/2.31 1/2.18 17/30.00 | |POLY-3 PERCENT (g) | 57.1% 41.8% 30.6% 0.0% 45.9% 56.7% | |INT SACRIFICE 1 (c)| 8/8 (100%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 6/6 (100%) | |TERMINAL (d) | 12/27 (44%) 2/5 (40%) 0/1 (0%) 0/1 (0%) 0/0 (0%) 11/24 (46%) | |FIRST INCIDENCE | 186 (I) 186 (I) 186 (I) --- 186 (I) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062 P=0.007N** P<0.001N** P<0.001N** P<0.001N** P=0.572 | |POLY 3 | P=0.492 P=0.394N P=0.419N P=0.298N P=0.578N P=0.583N | |POLY 1.5 | P=0.303 P=0.194N P=0.162N P=0.085N P=0.278N P=0.583N | |POLY 6 | P=0.556 P=0.515N P=0.575N P=0.459N P=0.549 P=0.583N | |LOGISTIC REGRESSION| P=0.058 P=0.006N** P<0.001N** P<0.001N** P<0.001N** (e) | |COCH-ARM / FISHERS | P=0.030 * P=0.016N* P=0.003N** P<0.001N** P=0.009N** P=0.584N | |ORDER RESTRICTED | P=0.262N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/35 (14%) 4/15 (27%) 1/12 (8%) 1/11 (9%) 0/10 (0%) 8/30 (27%) | |POLY-3 RATE (b) | 5/31.53 4/6.31 1/2.40 1/2.31 0/1.31 8/24.79 | |POLY-3 PERCENT (g) | 15.9% 63.4% 41.7% 43.2% 0.0% 32.3% | |INT SACRIFICE 1 (c)| 4/8 (50%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/6 (0%) | |TERMINAL (d) | 1/27 (4%) 4/5 (80%) 1/1 (100%) 1/1 (100%) 0/0 (0%) 8/24 (33%) | |FIRST INCIDENCE | 186 (I) 366 (T) 366 (T) 366 (T) --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.325 P=0.337 P=0.199N P=0.199N P=0.028N* P=0.170 | |POLY 3 | P=0.154 P=0.049 * P=0.472 P=0.465 P=0.624N P=0.129 | |POLY 1.5 | P=0.168 P=0.092 P=0.611 P=0.598 P=0.499N P=0.141 | |POLY 6 | P=0.133 P=0.034 * P=0.399 P=0.395 P=0.685N P=0.123 | |LOGISTIC REGRESSION| P=0.322 P=0.333 P=0.165N P=0.192N P=0.025N* P=0.166 | |COCH-ARM / FISHERS | P=0.120 P=0.254 P=0.514N P=0.555N P=0.266N P=0.175 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Pigmentation Hemosiderin | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/35 (17%) 0/15 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) 2/30 (7%) | |POLY-3 RATE (b) | 6/29.79 0/6.31 0/2.40 0/2.31 0/1.31 2/24.79 | |POLY-3 PERCENT (g) | 20.1% 0.0% 0.0% 0.0% 0.0% 8.1% | |INT SACRIFICE 1 (c)| 2/8 (25%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/6 (0%) | |TERMINAL (d) | 4/27 (15%) 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/0 (0%) 2/24 (8%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.327N P=0.101N P=0.163N P=0.163N P=0.185N P=0.189N | |POLY 3 | P=0.147N P=0.303N P=0.520N P=0.526N P=0.596N P=0.192N | |POLY 1.5 | P=0.220N P=0.222N P=0.377N P=0.391N P=0.449N P=0.189N | |POLY 6 | P=0.123N P=0.354N P=0.597N P=0.600N P=0.672N P=0.194N | |LOGISTIC REGRESSION| P=0.326N P=0.096N P=0.142N P=0.156N P=0.178N P=0.185N | |COCH-ARM / FISHERS | P=0.459N P=0.102N P=0.151N P=0.173N P=0.199N P=0.185N | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/3 (33%) 0/10 (0%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 1/3.00 0/1.31 0/1.31 0/2.31 0/1.31 2/2.13 | |POLY-3 PERCENT (g) | 33.3% 0.0% 0.0% 0.0% 0.0% 93.8% | |INT SACRIFICE 1 (c)| 1/1 (100%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/2 (50%) | |TERMINAL (d) | 0/2 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) 1/1 (100%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.019 * P=0.077N P=0.077N P=0.077N P=0.077N P=0.599 | |POLY 3 | P=0.003 ** P=0.637N P=0.637N P=0.553N P=0.637N P=0.327 | |POLY 1.5 | P<0.001 ** P=0.456N P=0.456N P=0.394N P=0.456N P=0.383 | |POLY 6 | P=0.005 ** P=0.727N P=0.727N P=0.644N P=0.727N P=0.297 | |LOGISTIC REGRESSION| P=0.012 * (e) (e) (e) (e) P=0.620 | |COCH-ARM / FISHERS | P=0.002 ** P=0.231N P=0.231N P=0.214N P=0.231N P=0.500 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Mesentery | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 2/2 (100%) 0/2 (0%) 2/2 (100%) 2/2 (100%) 0/1 (0%) | |POLY-3 RATE (b) | 1/1.00 2/2.00 0/0.22 2/2.00 2/2.00 0/0.13 | |POLY-3 PERCENT (g) | 100.0% 100.0% 0.0% 100.0% 100.0% 0.0% | |INT SACRIFICE 1 (c)| 0/0 (0%) 0/0 (0%) 0/1 (0%) 1/1 (100%) 0/0 (0%) 0/1 (0%) | |TERMINAL (d) | 1/1 (100%) 2/2 (100%) 0/0 (0%) 1/1 (100%) 2/2 (100%) 0/0 (0%) | |FIRST INCIDENCE | 366 (T) 366 (T) --- 186 (I) 366 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.559N (e) P=1.000 (e) (e) P=1.000 | |POLY 3 | P=1.000N (e) P=1.000N (e) (e) P=1.000 | |POLY 1.5 | P=0.955N (e) P=1.000N (e) (e) P=1.000 | |POLY 6 | P=1.000N (e) P=1.000N (e) (e) P=1.000 | |LOGISTIC REGRESSION| P=0.559N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.365N (e) P=0.333N (e) (e) P=0.500N | |ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/40 (20%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 9/40 (23%) | |POLY-3 RATE (b) | 8/31.31 0/1.31 0/1.40 0/1.31 0/1.31 9/32.18 | |POLY-3 PERCENT (g) | 25.6% 0.0% 0.0% 0.0% 0.0% 28.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 8/30 (27%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/30 (27%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407 P=1.000 P=1.000 P=1.000 P=1.000 P=0.500 | |POLY 3 | P=0.443 P=0.566N P=0.557N P=0.566N P=0.566N P=0.526 | |POLY 1.5 | P=0.324 P=0.394N P=0.376N P=0.394N P=0.394N P=0.518 | |POLY 6 | P=0.468 P=0.660N P=0.654N P=0.660N P=0.660N P=0.531 | |LOGISTIC REGRESSION| P=0.406 (e) (e) (e) (e) P=0.500 | |COCH-ARM / FISHERS | P=0.083 P=0.143N P=0.121N P=0.143N P=0.143N P=0.500 | |ORDER RESTRICTED | P=0.307 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 1/40 (3%) | |POLY-3 RATE (b) | 2/32.18 0/1.31 0/1.40 0/1.31 0/1.31 1/31.31 | |POLY-3 PERCENT (g) | 6.2% 0.0% 0.0% 0.0% 0.0% 3.2% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/30 (3%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/30 (3%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.551N P=0.500N P=0.500N P=0.500N P=0.500N P=0.500N | |POLY 3 | P=0.392N P=0.758N P=0.748N P=0.758N P=0.758N P=0.510N | |POLY 1.5 | P=0.450N P=0.703N P=0.689N P=0.703N P=0.703N P=0.507N | |POLY 6 | P=0.377N P=0.785N P=0.776N P=0.785N P=0.785N P=0.511N | |LOGISTIC REGRESSION| P=0.553N P=0.500N P=0.482N P=0.500N P=0.500N P=0.500N | |COCH-ARM / FISHERS | P=0.621N P=0.637N P=0.612N P=0.637N P=0.637N P=0.500N | |ORDER RESTRICTED | P=0.229N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 2/31.31 0/1.31 0/1.40 0/1.31 0/1.31 2/33.05 | |POLY-3 PERCENT (g) | 6.4% 0.0% 0.0% 0.0% 0.0% 6.1% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) | |TERMINAL (d) | 2/30 (7%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/30 (0%) | |FIRST INCIDENCE | 366 (T) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421 P=1.000 P=1.000 P=1.000 P=1.000 P=0.695 | |POLY 3 | P=0.612N P=0.757N P=0.747N P=0.757N P=0.757N P=0.675N | |POLY 1.5 | P=0.595 P=0.702N P=0.688N P=0.702N P=0.702N P=0.681N | |POLY 6 | P=0.593N P=0.785N P=0.776N P=0.785N P=0.785N P=0.672N | |LOGISTIC REGRESSION| P=0.417 (e) (e) (e) (e) P=0.698N | |COCH-ARM / FISHERS | P=0.418 P=0.637N P=0.612N P=0.637N P=0.637N P=0.692N | |ORDER RESTRICTED | P=0.659N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/40 (28%) 1/18 (6%) 0/14 (0%) 0/14 (0%) 1/14 (7%) 11/40 (28%) | |POLY-3 RATE (b) | 11/32.18 1/9.31 0/4.40 0/5.31 1/5.31 11/31.31 | |POLY-3 PERCENT (g) | 34.2% 10.7% 0.0% 0.0% 18.8% 35.1% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 10/30 (33%) 1/8 (13%) 0/3 (0%) 0/4 (0%) 1/4 (25%) 11/30 (37%) | |FIRST INCIDENCE | 186 (I) 366 (T) --- --- 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.225 P=0.148N P=0.161N P=0.120N P=0.387N P=0.602 | |POLY 3 | P=0.274 P=0.191N P=0.258N P=0.199N P=0.439N P=0.573 | |POLY 1.5 | P=0.174 P=0.129N P=0.139N P=0.112N P=0.298N P=0.582 | |POLY 6 | P=0.332 P=0.235N P=0.344N P=0.265N P=0.525N P=0.568 | |LOGISTIC REGRESSION| P=0.224 P=0.144N P=0.152N P=0.116N P=0.385N P=0.603N | |COCH-ARM / FISHERS | P=0.058 P=0.053N P=0.024N* P=0.024N* P=0.111N P=0.599N | |ORDER RESTRICTED | P=0.082 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/18 (0%) 1/14 (7%) 0/14 (0%) 0/14 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 1/32.18 0/9.31 1/4.40 0/5.31 0/5.31 2/32.18 | |POLY-3 PERCENT (g) | 3.1% 0.0% 22.7% 0.0% 0.0% 6.2% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/30 (0%) 0/8 (0%) 1/3 (33%) 0/4 (0%) 0/4 (0%) 1/30 (3%) | |FIRST INCIDENCE | 186 (I) --- 366 (T) --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.316 P=0.500N P=0.563 P=0.500N P=0.500N P=0.500 | |POLY 3 | P=0.383 P=0.720N P=0.341 P=0.784N P=0.784N P=0.500 | |POLY 1.5 | P=0.376 P=0.701N P=0.396 P=0.762N P=0.762N P=0.500 | |POLY 6 | P=0.383 P=0.731N P=0.313 P=0.796N P=0.796N P=0.500 | |LOGISTIC REGRESSION| P=0.312 (e) P=0.580 (e) (e) P=0.500 | |COCH-ARM / FISHERS | P=0.335 P=0.690N P=0.455 P=0.741N P=0.741N P=0.500 | |ORDER RESTRICTED | P=0.231 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Preputial Gland | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/39 (5%) 0/10 (0%) 0/10 (0%) 2/12 (17%) 0/10 (0%) 1/40 (3%) | |POLY-3 RATE (b) | 2/30.31 0/1.31 0/1.31 2/3.31 0/1.31 1/31.31 | |POLY-3 PERCENT (g) | 6.6% 0.0% 0.0% 60.4% 0.0% 3.2% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/29 (7%) 0/0 (0%) 0/0 (0%) 2/2 (100%) 0/0 (0%) 1/30 (3%) | |FIRST INCIDENCE | 366 (T) --- --- 366 (T) --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.193N P=1.000 P=1.000N P=0.004 ** P=1.000 P=0.488N | |POLY 3 | P=0.281N P=0.754N P=0.754N P=0.087 P=0.754N P=0.489N | |POLY 1.5 | P=0.286N P=0.697N P=0.697N P=0.129 P=0.697N P=0.489N | |POLY 6 | P=0.296N P=0.782N P=0.782N P=0.069 P=0.782N P=0.488N | |LOGISTIC REGRESSION| P=0.193N (e) (e) P=0.004 ** (e) P=0.488N | |COCH-ARM / FISHERS | P=0.378N P=0.630N P=0.630N P=0.232 P=0.630N P=0.490N | |ORDER RESTRICTED | P=0.034N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/39 (8%) 0/10 (0%) 0/10 (0%) 2/12 (17%) 0/10 (0%) 0/40 (0%) | |POLY-3 RATE (b) | 3/31.18 0/1.31 0/1.31 2/3.31 0/1.31 0/31.31 | |POLY-3 PERCENT (g) | 9.6% 0.0% 0.0% 60.4% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/29 (7%) 0/0 (0%) 0/0 (0%) 2/2 (100%) 0/0 (0%) 0/30 (0%) | |FIRST INCIDENCE | 186 (I) --- --- 366 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.052N P=0.500N P=0.500N P=0.139 P=0.500N P=0.119N | |POLY 3 | P=0.043N* P=0.698N P=0.698N P=0.131 P=0.698N P=0.116N | |POLY 1.5 | P=0.047N* P=0.615N P=0.615N P=0.193 P=0.615N P=0.115N | |POLY 6 | P=0.047N* P=0.739N P=0.739N P=0.103 P=0.739N P=0.116N | |LOGISTIC REGRESSION| P=0.050N P=0.500N P=0.500N P=0.134 P=0.500N P=0.115N | |COCH-ARM / FISHERS | P=0.093N P=0.496N P=0.496N P=0.335 P=0.496N P=0.116N | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Prostate | | Corpora Amylacea | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/40 (3%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 1/32.18 0/1.31 0/1.40 0/1.31 0/1.31 2/33.05 | |POLY-3 PERCENT (g) | 3.1% 0.0% 0.0% 0.0% 0.0% 6.1% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) | |TERMINAL (d) | 0/30 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/30 (0%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062 P=0.500N P=0.500N P=0.500N P=0.500N P=0.500 | |POLY 3 | P=0.372 P=0.856N P=0.847N P=0.856N P=0.856N P=0.509 | |POLY 1.5 | P=0.347 P=0.835N P=0.823N P=0.835N P=0.835N P=0.506 | |POLY 6 | P=0.373 P=0.866N P=0.857N P=0.866N P=0.866N P=0.511 | |LOGISTIC REGRESSION| P=0.056 (e) P=0.470N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.238 P=0.800N P=0.784N P=0.800N P=0.800N P=0.500 | |ORDER RESTRICTED | P=0.230 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Prostate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/40 (0%) 0/10 (0%) 0/11 (0%) 0/10 (0%) 0/10 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 0/31.31 0/1.31 0/1.40 0/1.31 0/1.31 2/31.31 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 6.4% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/30 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/30 (7%) | |FIRST INCIDENCE | --- --- --- --- --- 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 (e) (e) (e) (e) P=0.238 | |POLY 3 | P=0.098 (e) (e) (e) (e) P=0.236 | |POLY 1.5 | P=0.096 (e) (e) (e) (e) P=0.236 | |POLY 6 | P=0.096 (e) (e) (e) (e) P=0.236 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.238 | |COCH-ARM / FISHERS | P=0.073 (e) (e) (e) (e) P=0.247 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Spleen | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 1/13 (8%) 1/12 (8%) 2/13 (15%) 3/13 (23%) 2/40 (5%) | |POLY-3 RATE (b) | 2/31.31 1/4.31 1/2.40 2/4.31 3/4.31 2/31.31 | |POLY-3 PERCENT (g) | 6.4% 23.2% 41.7% 46.4% 69.6% 6.4% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/30 (7%) 1/3 (33%) 1/1 (100%) 2/3 (67%) 3/3 (100%) 2/30 (7%) | |FIRST INCIDENCE | 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174N P=0.319 P=0.086 P=0.019 * P<0.001 ** P=0.696 | |POLY 3 | P=0.374N P=0.427 P=0.351 P=0.110 P=0.015 * P=0.695 | |POLY 1.5 | P=0.348N P=0.497 P=0.436 P=0.152 P=0.027 * P=0.695 | |POLY 6 | P=0.411N P=0.389 P=0.307 P=0.091 P=0.011 * P=0.695 | |LOGISTIC REGRESSION| P=0.174N P=0.319 P=0.086 P=0.019 * P<0.001 ** P=0.696 | |COCH-ARM / FISHERS | P=0.408N P=0.578 P=0.553 P=0.249 P=0.088 P=0.692N | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/40 (65%) 31/40 (78%) 31/40 (78%) 31/40 (78%) 32/39 (82%) 40/40 (100%) | |POLY-3 RATE (b) | 26/32.18 31/32.18 31/33.01 31/32.18 32/32.92 40/40.00 | |POLY-3 PERCENT (g) | 80.8% 96.3% 93.9% 96.3% 97.2% 100.0% | |INT SACRIFICE 1 (c)| 1/10 (10%) 1/10 (10%) 3/10 (30%) 1/10 (10%) 3/10 (30%) 10/10 (100%) | |TERMINAL (d) | 25/30 (83%) 30/30 (100%) 28/29 (97%) 30/30 (100%) 29/29 (100%) 30/30 (100%) | |FIRST INCIDENCE | 186 (I) 186 (I) 186 (I) 186 (I) 186 (I) 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.059 P=0.050 P=0.059 P=0.018 * P<0.001 ** | |POLY 3 | P=0.006 ** P=0.033 * P=0.083 P=0.033 * P=0.022 * P=0.003 ** | |POLY 1.5 | P<0.001 ** P=0.059 P=0.095 P=0.059 P=0.028 * P<0.001 ** | |POLY 6 | P=0.056 P=0.028 * P=0.089 P=0.028 * P=0.025 * P=0.011 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.057 P=0.052 P=0.057 P=0.017 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.162 P=0.162 P=0.162 P=0.072 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/15/04 EXPERIMENT: 05135 TEST: 05 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ISOPRENE Terminal Sacrifice at 53 weeks |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 3/40 (8%) | |POLY-3 RATE (b) | 2/33.05 0/1.31 0/1.31 0/1.31 0/1.31 3/32.18 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 0.0% 0.0% 9.3% | |INT SACRIFICE 1 (c)| 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/30 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/30 (7%) | |FIRST INCIDENCE | 186 (I) --- --- --- --- 186 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.158 P=0.234N P=0.234N P=0.234N P=0.234N P=0.500 | |POLY 3 | P=0.375 P=0.759N P=0.759N P=0.759N P=0.759N P=0.488 | |POLY 1.5 | P=0.341 P=0.705N P=0.705N P=0.705N P=0.705N P=0.492 | |POLY 6 | P=0.376 P=0.784N P=0.784N P=0.784N P=0.784N P=0.486 | |LOGISTIC REGRESSION| P=0.156 (e) (e) (e) (e) P=0.500 | |COCH-ARM / FISHERS | P=0.209 P=0.637N P=0.637N P=0.637N P=0.637N P=0.500 | |ORDER RESTRICTED | P=0.252 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Males | |Dose | CONTROL 70 PPM 220 PPM 700 PPM 2200 PPM 7000 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Calculus Micro Observation Only | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/40 (5%) 0/11 (0%) 3/13 (23%) 0/10 (0%) 5/17 (29%) 12/40 (30%) | |POLY-3 RATE (b) | 2/31.31 0/2.31 3/4.31 0/1.31 5/8.31 12/31.31 | |POLY-3 PERCENT (g) | 6.4% 0.0% 69.6% 0.0% 60.2% 38.3% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/30 (7%) 0/1 (0%) 3/3 (100%) 0/0 (0%) 5/7 (71%) 12/30 (40%) | |FIRST INCIDENCE | 366 (T) --- 366 (T) --- 366 (T) 366 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.038 * P=0.962N P<0.001 ** P=1.000N P<0.001 ** P=0.003 ** | |POLY 3 | P=0.003 ** P=0.724N P=0.015 * P=0.757N P=0.002 ** P=0.002 ** | |POLY 1.5 | P=0.003 ** P=0.669N P=0.027 * P=0.702N P=0.003 ** P=0.002 ** | |POLY 6 | P=0.003 ** P=0.752N P=0.011 * P=0.785N P<0.001 ** P=0.002 ** | |LOGISTIC REGRESSION| P=0.038 * (e) P<0.001 ** (e) P<0.001 ** P=0.003 ** | |COCH-ARM / FISHERS | P=0.002 ** P=0.612N P=0.088 P=0.637N P=0.020 * P=0.003 ** | |ORDER RESTRICTED | P<0.001 ** (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).