TDMS Study 92012-05 Pathology Tables
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 FINAL#1; REVISION#1 Facility: Southern Research Institute Chemical CAS #: 693-98-1 Lock Date: 10/16/01 Cage Range: All Reasons For Removal: 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice Removal Date Range: All Treatment Groups: Include All a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 1 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 60 60 60 60 Early Deaths Natural Death 4 3 10 1 Moribund Sacrifice 6 8 12 7 Survivors Terminal Sacrifice 40 39 28 41 Natural Death 1 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Cecum (48) (47) (44) (50) Edema 1 [3.0] Intestine Small, Jejunum (47) (46) (44) (49) Necrosis, Focal 1 [3.0] Liver (50) (49) (50) (50) Angiectasis, Focal 2 [2.0] 1 [2.0] 2 [3.5] Basophilic Focus 42 44 43 39 Cholangiofibrosis 1 [2.0] Congestion 2 [2.5] 1 [4.0] Congestion, Focal 1 [2.0] Degeneration, Cystic, Focal 1 [2.0] 2 [2.0] Eosinophilic Focus 1 Fatty Change 2 [3.0] 1 [2.0] Hemorrhage 2 [2.0] 2 [2.0] Hepatodiaphragmatic Nodule 6 11 14 13 Hyperplasia, Focal, Lymphoid 1 [3.0] 1 [2.0] Infarct 2 Infiltration Cellular, Mixed Cell 42 [1.7] 44 [2.0] 34 [1.9] 38 [1.9] Inflammation, Granulomatous 18 [1.6] 23 [2.0] 22 [1.5] 42 [2.1] Mixed Cell Focus 15 14 11 26 Necrosis, Focal 1 [2.0] 1 [2.0] Bile Duct, Cholangiofibrosis, Focal 1 [2.0] Bile Duct, Cyst 2 Bile Duct, Cyst, Multiple 1 1 Bile Duct, Hyperplasia 20 [1.3] 29 [1.4] 20 [1.5] 40 [1.9] Hepatocyte, Necrosis, Focal 1 [2.0] 2 [2.0] Hepatocyte, Vacuolization Cytoplasmic, Focal 9 [1.4] 10 [1.4] 11 [1.2] 9 [1.8] Hepatocyte, Periportal, Vacuolization Cytoplasmic 1 [2.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 2 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Hepatocyte, Centrilobular, Necrosis 1 [3.0] 1 [3.0] Hepatocyte, Centrilobular, Vacuolization Cytoplasmic 1 [4.0] 4 [3.0] 1 [2.0] Mesentery (8) (10) (12) (9) Fibrosis 1 [1.0] Hemorrhage, Focal 1 [2.0] Infiltration Cellular, Mixed Cell 1 [2.0] Inflammation, Chronic 1 [2.0] Artery, Inflammation, Chronic, Focal 1 [3.0] Fat, Necrosis 1 [2.0] 2 [2.5] Fat, Necrosis, Focal 5 [2.0] 7 [2.7] 6 [2.8] 3 [2.0] Pancreas (50) (49) (49) (50) Infiltration Cellular, Diffuse, Mixed Cell 1 [2.0] Acinus, Atrophy, Diffuse 1 [3.0] 1 [4.0] 1 [2.0] Acinus, Atrophy, Focal 13 [1.6] 14 [1.2] 13 [1.7] 11 [1.9] Duct, Cyst, Focal 1 [2.0] 1 [2.0] Duct, Cyst, Focal, Multiple 9 [1.8] 12 [1.9] 4 [2.0] 5 [1.8] Salivary Glands (50) (49) (50) (50) Duct, Mineralization, Focal 2 [2.5] Stomach, Forestomach (50) (50) (50) (50) Diverticulum 1 [2.0] 1 [2.0] 2 [1.5] Edema 1 [3.0] Erosion 1 [2.0] Inflammation, Chronic 1 [3.0] 1 [3.0] Inflammation, Focal 1 [2.0] Ulcer 2 [2.5] 1 [2.0] 1 [2.0] Epithelium, Hyperplasia 3 [1.3] 1 [2.0] 4 [2.5] 1 [2.0] Stomach, Glandular (49) (49) (48) (50) Erosion 1 [2.0] 1 [2.0] Inflammation, Chronic 1 [2.0] Necrosis, Focal 1 [2.0] Ulcer 1 [2.0] Epithelium, Hyperplasia, Focal 1 [2.0] Glands, Degeneration, Cystic, Focal 1 [1.0] Glands, Ectasia, Focal 1 [2.0] Glands, Hyperplasia, Focal 2 [2.0] Tongue (3) (1) Epithelium, Hyperplasia, Focal 1 [1.0] Tooth (1) Peridontal Tissue, Inflammation, Chronic 1 [2.0] ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 3 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (49) (50) (50) Cardiomyopathy 5 [1.4] 8 [1.9] 7 [1.6] 6 [1.7] Infiltration Cellular, Mixed Cell 4 [1.5] 3 [2.0] 2 [1.5] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (49) (50) (50) Accessory Adrenal Cortical Nodule 2 [1.0] 2 [1.0] 5 [1.2] 5 [1.0] Angiectasis 1 [2.0] 1 [3.0] 1 [2.0] 2 [2.0] Cytoplasmic Alteration, Focal 3 [1.7] 1 [1.0] 5 [1.4] Hematopoietic Cell Proliferation 1 [2.0] Hemorrhage 1 [2.0] Hemorrhage, Focal 1 [2.0] Vacuolization Cytoplasmic, Focal 8 [1.8] 3 [2.0] 7 [1.9] 12 [1.6] Adrenal Medulla (49) (49) (50) (50) Hyperplasia, Focal 1 [2.0] 1 [2.0] 1 [1.0] 2 [1.0] Pituitary Gland (50) (48) (50) (50) Angiectasis 5 [2.8] 9 [2.6] 7 [2.7] 2 [3.0] Cyst 1 [3.0] Hemorrhage 1 [3.0] Metaplasia, Focal, Lipocyte 1 [2.0] Pars Distalis, Angiectasis 1 [2.0] Pars Distalis, Cyst 1 [3.0] 3 [2.3] 2 [2.0] 1 [2.0] Pars Distalis, Cyst, Multiple 2 [2.5] Pars Distalis, Cytoplasmic Alteration, Focal 4 [1.5] 4 [1.5] 1 [2.0] 3 [1.7] Pars Distalis, Degeneration, Cystic 1 [2.0] Pars Distalis, Degeneration, Cystic, Focal 9 [2.2] 14 [2.1] 8 [2.4] 5 [2.2] Pars Distalis, Hemorrhage, Focal 1 [1.0] 3 [2.7] 4 [3.0] 6 [2.7] Pars Distalis, Hyperplasia, Focal 1 [2.0] 1 [2.0] 1 [3.0] 1 [2.0] Pars Distalis, Pigmentation, Focal 1 [2.0] Pars Intermedia, Cyst 1 [2.0] 3 [2.0] Pars Intermedia, Degeneration, Cystic, Focal 1 [2.0] Pars Intermedia, Hemorrhage 1 [2.0] Pars Intermedia, Pars Nervosa, Atypia Cellular, Focal 1 [2.0] Rathke's Cleft, Cyst 1 [3.0] 1 [2.0] Rathke's Cleft, Hemorrhage 2 [3.0] Thyroid Gland (49) (48) (42) (48) Vacuolization Cytoplasmic, Focal 1 [1.0] C-Cell, Hyperplasia 48 [2.2] 46 [2.2] 40 [2.0] 25 [1.7] Follicle, Cyst 2 1 a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 4 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Follicle, Mineralization, Focal 42 [1.0] 47 [1.7] 41 [2.4] 48 [2.7] Follicular Cell, Hyperplasia 41 [1.5] 34 [1.7] 46 [2.2] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (3) (4) (2) Mediastinum, Infiltration Cellular, Mixed Cell 1 [3.0] Pelvic, Hemorrhage, Focal 1 [3.0] Thoracic, Infiltration Cellular, Focal, Mixed Cell 1 [3.0] ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (49) (50) (50) Degeneration, Cystic 6 [2.5] 4 [3.0] 1 [2.0] 1 [3.0] Fibrosis, Focal 1 [2.0] Hyperplasia, Cystic 1 [2.0] 4 [2.8] 3 [3.0] 1 [3.0] Inflammation, Chronic 2 [3.0] 5 [2.2] 4 [2.3] Ovary (50) (49) (50) (50) Angiectasis 1 [2.0] 1 [2.0] Atrophy 1 [3.0] Congestion 1 [3.0] Cyst 5 [2.0] 5 [2.8] 1 [2.0] Bilateral, Cyst, Multiple 1 [4.0] Periovarian Tissue, Cyst 4 [3.3] 5 [3.2] 4 [3.0] 6 [3.0] Periovarian Tissue, Cyst, Multiple 1 [2.0] Uterus (50) (50) (50) (50) Cyst 3 [2.7] 1 [2.0] 1 [2.0] Hemorrhage 2 [2.0] Inflammation, Chronic 1 [3.0] Cervix, Hyperplasia 1 [3.0] Endometrium, Hyperplasia, Cystic 10 [1.7] 14 [1.8] 15 [1.6] 15 [1.6] Vagina (2) (2) Inflammation, Chronic 1 [2.0] Epithelium, Cyst 1 [3.0] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (49) (50) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 5 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Atrophy 1 [3.0] Fibrosis 1 [3.0] Hyperplasia, Focal, Histiocytic 1 [2.0] 4 [2.3] Myelofibrosis 1 [3.0] Necrosis 1 [2.0] Myeloid Cell, Hyperplasia 2 [3.0] 3 [2.7] 5 [2.6] 2 [3.0] Myeloid Cell, Erythroid Cell, Hyperplasia 2 [2.5] 1 [3.0] Lymph Node (32) (31) (34) (41) Deep Cervical, Hemorrhage 2 [3.0] Mediastinal, Angiectasis 1 [3.0] Mediastinal, Congestion 1 [3.0] Mediastinal, Ectasia 5 [2.8] 3 [2.7] 2 [3.0] 7 [2.9] Mediastinal, Hemorrhage 2 [2.0] 3 [3.0] 9 [2.8] 8 [2.9] Mediastinal, Hyperplasia 1 [3.0] 2 [3.0] Mediastinal, Hyperplasia, Histiocytic 8 [2.9] 8 [2.9] 5 [3.0] 12 [3.0] Mediastinal, Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] 1 [3.0] Mediastinal, Pigmentation 1 [2.0] 2 [3.0] Pancreatic, Atrophy 1 [3.0] Pancreatic, Ectasia 2 [2.0] 2 [3.0] 11 [2.7] Pancreatic, Hemorrhage 5 [2.6] 3 [3.0] 2 [2.5] 9 [3.0] Pancreatic, Hyperplasia, Histiocytic 16 [2.8] 24 [2.8] 17 [3.0] 18 [3.1] Pancreatic, Hyperplasia, Plasma Cell 1 [3.0] Pancreatic, Infiltration Cellular, Mixed Cell 1 [3.0] Pancreatic, Pigmentation 4 [2.8] 2 [2.5] 1 [3.0] Lymph Node, Mandibular (5) (4) (5) (1) Ectasia 1 [3.0] Lymph Node, Mesenteric (49) (49) (49) (50) Angiectasis 1 [3.0] Ectasia 1 [3.0] 5 [3.0] Hemorrhage 1 [2.0] 2 [3.0] 2 [3.0] Hyperplasia, Histiocytic 2 [3.0] 1 [3.0] 2 [3.0] 2 [3.0] Hyperplasia, Lymphoid 1 [3.0] Pigmentation 2 [2.5] Spleen (50) (49) (48) (50) Accessory Spleen 1 [1.0] 1 [2.0] Angiectasis, Focal 1 [2.0] Congestion 1 [3.0] Fibrosis, Focal 1 [2.0] 1 [2.0] Hematopoietic Cell Proliferation 6 [2.2] 8 [2.4] 5 [2.6] 4 [2.0] Hemorrhage 1 [2.0] Infarct 1 [3.0] Inflammation, Granulomatous 3 [3.3] 2 [3.0] 4 [2.5] 27 [3.3] Pigmentation 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 6 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Pigmentation, Focal 1 [2.0] 1 [3.0] 1 [3.0] Thymus (48) (45) (49) (49) Angiectasis 2 [3.0] Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] 2 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) Dilatation 33 [2.4] 35 [2.5] 22 [2.6] 19 [2.3] Ectasia 2 [3.5] 3 [2.3] 7 [2.3] Fibrosis 1 [3.0] Hyperplasia 3 [2.3] 5 [2.6] 4 [2.0] 3 [2.0] Hyperplasia, Cystic 1 [3.0] 2 [2.5] Inflammation, Focal 1 [3.0] Skin (50) (50) (50) (50) Necrosis, Focal 4 [3.3] Ulcer 1 [3.0] 1 [4.0] Subcutaneous Tissue, Angiectasis, Focal 1 [2.0] Subcutaneous Tissue, Hemorrhage, Focal 1 [3.0] Subcutaneous Tissue, Inflammation, Focal, Suppurative 1 [3.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (49) (50) (50) Compression, Focal 10 [2.9] 8 [3.0] 12 [2.9] 4 [3.0] Hemorrhage, Focal 2 [2.5] 1 [2.0] 2 [3.0] Necrosis, Focal 2 [3.0] Pigmentation, Focal 1 [2.0] Cerebellum, Developmental Malformation 1 [3.0] Spinal Cord (3) (1) (4) Hemorrhage, Focal 1 [2.0] Necrosis, Focal 1 [2.0] ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 7 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) (50) (50) Congestion 2 [1.5] 4 [2.3] 2 [2.0] 2 [1.5] Emphysema 1 [3.0] Hemorrhage 1 [1.0] Hemorrhage, Focal 1 [2.0] 2 [2.5] Hyperplasia, Focal, Histiocytic 1 [1.0] 1 [3.0] Hyperplasia, Histiocytic 6 [1.3] 6 [1.2] 7 [1.0] 1 [2.0] Infiltration Cellular, Focal, Mixed Cell 1 [2.0] Infiltration Cellular, Mixed Cell 3 [2.0] 1 [3.0] 6 [2.0] Inflammation, Chronic, Focal 1 [1.0] 2 [1.0] 1 [2.0] Inflammation, Focal, Granulomatous 1 [1.0] 1 [1.0] Pigmentation, Focal 1 [2.0] Alveolar Epithelium, Hyperplasia, Focal 7 [1.6] 5 [1.8] 3 [1.7] 3 [2.0] Alveolus, Inflammation, Focal, Granulomatous 1 [2.0] Interstitium, Edema 1 [3.0] Nose (50) (49) (50) (50) Foreign Body 1 [2.0] 1 [3.0] Inflammation, Suppurative 1 [2.0] 1 [2.0] 2 [2.5] Nasolacrimal Duct, Inflammation 4 [2.8] 2 [2.0] 4 [2.3] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (49) (49) (50) Atrophy 1 [3.0] 1 [3.0] 1 [3.0] Cataract 1 [3.0] 2 [3.0] 2 [1.5] 1 [3.0] Iris, Synechia 1 [3.0] Retina, Degeneration 2 [3.0] 1 [3.0] 1 [3.0] Harderian Gland (50) (49) (50) (50) Hyperplasia, Cystic, Focal 1 [2.0] Hyperplasia, Focal 2 [1.0] 1 [2.0] 1 [1.0] Hyperplasia, Focal, Histiocytic 1 [2.0] 2 [1.5] 1 [2.0] 4 [1.5] Inflammation, Chronic, Focal 3 [1.3] 1 [3.0] Inflammation, Focal, Granulomatous 1 [1.0] Epithelium, Hyperplasia, Focal 2 [1.5] 2 [2.0] 1 [1.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (48) (47) (50) Atrophy, Focal 2 [2.0] 1 [2.0] Congestion 2 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 8 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Cyst 1 [2.0] Infarct 1 [2.0] Nephropathy 38 [1.0] 40 [1.0] 38 [1.1] 40 [1.1] Glomerulus, Amyloid Deposition, Diffuse 1 [3.0] Pelvis, Inflammation 1 [2.0] Renal Tubule, Accumulation, Hyaline Droplet 11 [2.2] 7 [2.0] 3 [2.3] 4 [2.5] Renal Tubule, Pigmentation 8 [1.6] 4 [1.5] 5 [2.2] Urethra (2) Transitional Epithelium, Hyperplasia, Diffuse 1 [2.0] Urinary Bladder (50) (49) (49) (50) Transitional Epithelium, Hyperplasia 2 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 9 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 60 60 60 60 Early Deaths Moribund Sacrifice 13 6 7 13 Natural Death 2 4 7 2 Survivors Terminal Sacrifice 34 39 35 35 Moribund Sacrifice 1 Natural Death 1 1 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Rectum (49) (48) (48) (50) Angiectasis, Focal 1 [2.0] Liver (50) (50) (50) (50) Angiectasis, Focal 1 [3.0] Basophilic Focus 23 23 8 2 Cholangiofibrosis 1 [4.0] 1 [2.0] Congestion 2 [3.0] 1 [3.0] Degeneration, Cystic, Focal 4 [1.8] 3 [1.3] 2 [2.0] 7 [1.7] Eosinophilic Focus 3 6 1 Fibrosis, Focal 1 [3.0] Hematopoietic Cell Proliferation 2 [1.0] Hepatodiaphragmatic Nodule 6 5 4 9 Hyperplasia, Focal, Lymphoid 1 [2.0] 2 [2.0] 1 [3.0] Infiltration Cellular, Mixed Cell 25 [2.0] 30 [1.9] 27 [1.9] 36 [1.9] Inflammation, Granulomatous 12 [1.3] 11 [1.2] 4 [1.8] 11 [1.4] Mixed Cell Focus 14 16 23 26 Necrosis, Focal 2 [2.5] 2 [2.5] 1 [2.0] Pigmentation, Focal 2 [2.5] Bile Duct, Cyst 1 Bile Duct, Hyperplasia 49 [2.7] 49 [2.6] 47 [2.7] 49 [2.8] Centrilobular, Congestion 1 [3.0] Hepatocyte, Necrosis, Focal 1 [4.0] 1 [1.0] 3 [2.0] 2 [1.5] Hepatocyte, Vacuolization Cytoplasmic, Diffuse 1 [2.0] 1 [2.0] Hepatocyte, Vacuolization Cytoplasmic, Focal 23 [1.8] 30 [1.8] 26 [1.7] 23 [1.6] Hepatocyte, Centrilobular, Necrosis 2 [2.5] 2 [2.5] Hepatocyte, Centrilobular, Vacuolization Cytoplasmic 5 [2.8] 4 [2.8] 3 [2.3] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 10 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Hepatocyte, Midzonal, Vacuolization Cytoplasmic 1 [2.0] 1 [2.0] 2 [2.5] Oval Cell, Hyperplasia 1 [2.0] Serosa, Fibrosis, Focal 2 [2.5] Mesentery (26) (46) (35) (20) Fibrosis, Focal 1 [3.0] Hemorrhage 2 [3.5] Necrosis, Focal 1 [3.0] Artery, Inflammation, Chronic 1 [3.0] Fat, Necrosis 1 [2.0] 1 [3.0] 2 [2.5] Fat, Necrosis, Focal 8 [2.9] 10 [2.7] 16 [2.8] 10 [2.7] Pancreas (49) (49) (50) (50) Atrophy, Diffuse 1 [3.0] Atrophy, Focal 1 [2.0] 1 [2.0] Fibrosis, Focal 1 [3.0] Acinus, Atrophy, Diffuse 1 [4.0] 1 [3.0] Acinus, Atrophy, Focal 22 [1.9] 27 [1.9] 20 [2.0] 36 [2.0] Acinus, Hyperplasia, Focal 1 [3.0] Duct, Cyst 1 [1.0] Duct, Cyst, Focal 1 [4.0] Duct, Cyst, Focal, Multiple 6 [2.7] 2 [2.0] 5 [2.0] 12 [1.9] Duct, Hyperplasia, Cystic 1 [2.0] 1 [2.0] Duct, Hyperplasia, Cystic, Focal 2 [2.0] 3 [2.0] Duct, Hyperplasia, Focal 1 [2.0] Salivary Glands (50) (50) (50) (50) Atrophy, Focal 1 [1.0] Inflammation, Chronic 1 [2.0] Stomach, Forestomach (50) (50) (50) (49) Diverticulum 1 [1.0] 1 [1.0] 2 [1.5] 1 [2.0] Edema 1 [3.0] Erosion 1 [2.0] 1 [1.0] Inflammation, Focal 1 [2.0] 1 [2.0] Ulcer 2 [1.5] 1 [2.0] 1 [2.0] 4 [2.0] Epithelium, Hyperplasia 2 [2.0] 3 [2.7] 6 [2.0] Epithelium, Hyperplasia, Focal 1 [2.0] Serosa, Foreign Body 1 [1.0] Serosa, Inflammation, Chronic, Focal 1 [2.0] Stomach, Glandular (50) (50) (50) (49) Erosion 4 [1.8] 1 [1.0] 1 [2.0] Erosion, Focal 1 [2.0] 1 [3.0] Inflammation, Focal 1 [2.0] Ulcer 2 [1.0] Epithelium, Necrosis, Focal 1 [1.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 11 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Glands, Hyperplasia, Cystic, Focal 1 [2.0] Glands, Hyperplasia, Focal 1 [1.0] Tongue (1) (2) (1) Epithelium, Hyperplasia, Focal 1 [2.0] Tooth (1) (1) (1) (2) Malformation 1 [2.0] Peridontal Tissue, Inflammation 1 [3.0] Peridontal Tissue, Inflammation, Chronic 1 [2.0] Peridontal Tissue, Inflammation, Focal, Suppurative 1 [3.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) Cardiomyopathy 3 [1.7] 5 [1.6] 10 [2.0] 5 [2.0] Cardiomyopathy, Focal 2 [2.0] 1 [2.0] Congestion 1 [3.0] Fibrosis 1 [2.0] Infiltration Cellular, Mixed Cell 1 [2.0] Thrombosis 1 [3.0] 1 [3.0] Endocardium, Myocardium, Fibrosis, Focal 1 [3.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 1 [2.0] 4 [1.3] 9 [1.1] 5 [1.6] Cytoplasmic Alteration, Focal 2 [2.0] 1 [1.0] 1 [1.0] 3 [1.3] Degeneration, Cystic, Focal 1 [2.0] Hemorrhage 2 [1.5] Vacuolization Cytoplasmic, Focal 6 [1.5] 9 [1.4] 10 [1.3] 10 [1.4] Adrenal Medulla (50) (50) (50) (50) Angiectasis 1 [2.0] Hyperplasia 1 [2.0] 1 [1.0] 1 [2.0] Hyperplasia, Focal 7 [1.3] 5 [2.2] 3 [1.3] 7 [1.4] Infiltration Cellular, Lymphoid 1 [2.0] Vacuolization Cytoplasmic, Focal 1 [2.0] Islets, Pancreatic (50) (49) (50) (50) Atrophy 1 [3.0] Hyperplasia, Focal 2 [2.0] 1 [3.0] 1 [2.0] Parathyroid Gland (47) (49) (48) (49) Cyst 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 12 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hyperplasia 1 [3.0] Hyperplasia, Focal 1 [2.0] 1 [3.0] Bilateral, Hyperplasia, Focal 1 [2.0] Pituitary Gland (50) (50) (50) (50) Angiectasis 2 [1.5] 3 [2.7] Pars Distalis, Angiectasis 3 [2.3] 2 [2.5] 2 [2.0] 1 [2.0] Pars Distalis, Cyst 1 [2.0] 4 [1.3] 2 [2.5] 3 [2.0] Pars Distalis, Cytoplasmic Alteration, Focal 1 [1.0] 4 [1.8] 2 [1.5] 5 [1.0] Pars Distalis, Degeneration, Cystic, Focal 1 [2.0] 1 [2.0] 1 [2.0] 1 [1.0] Pars Distalis, Hyperplasia, Focal 2 [1.5] 1 [2.0] 2 [1.5] Pars Distalis, Inflammation, Chronic, Focal, Granulomatous 1 [2.0] Pars Distalis, Pars Intermedia, Angiectasis 1 [3.0] Pars Intermedia, Cyst 2 [1.5] 1 [2.0] Pars Intermedia, Hemorrhage 1 [2.0] Pars Intermedia, Hyperplasia, Focal 1 [1.0] Pars Nervosa, Infiltration Cellular, Focal, Mixed Cell 1 [2.0] Thyroid Gland (48) (46) (43) (50) Cyst 1 C-Cell, Hyperplasia 41 [1.7] 43 [1.7] 38 [1.5] 34 [1.7] Follicle, Cyst 1 1 Follicle, Mineralization, Focal 48 [1.0] 45 [1.0] 43 [1.9] 49 [2.7] Follicular Cell, Atrophy, Focal 1 [1.0] Follicular Cell, Hyperplasia 17 [1.1] 37 [1.1] 43 [1.8] Follicular Cell, Hyperplasia, Cystic, Focal 1 [2.0] 1 [2.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (7) (2) (6) (4) Mediastinum, Hemorrhage 1 [3.0] Thoracic, Hemorrhage 1 [3.0] ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (50) (50) (50) (50) Atrophy 1 [3.0] 1 [2.0] Granuloma Sperm 1 [2.0] 1 [4.0] 1 [2.0] Inflammation, Chronic 1 [3.0] 1 [2.0] Preputial Gland (50) (50) (50) (50) Cyst 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 13 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Degeneration, Cystic 2 [2.5] Hyperplasia 1 [2.0] Hyperplasia, Cystic 2 [3.0] 2 [3.0] 1 [4.0] Hyperplasia, Focal 1 [2.0] Inflammation, Chronic 4 [2.0] 10 [1.6] 10 [1.7] 11 [2.0] Inflammation, Chronic, Focal 1 [1.0] Inflammation, Suppurative 1 [3.0] 1 [3.0] 2 [3.5] Prostate (50) (50) (50) (50) Atrophy 1 [3.0] Hyperplasia, Focal 1 [1.0] Inflammation, Chronic 15 [1.8] 10 [1.9] 17 [1.6] 19 [1.5] Epithelium, Degeneration, Focal, Mucoid 1 [2.0] Epithelium, Hyperplasia, Focal 4 [1.3] 2 [1.5] 5 [1.2] Testes (50) (50) (50) (50) Atrophy 5 [3.2] 4 [3.8] 13 [3.1] 13 [3.2] Mineralization, Focal 1 [1.0] Bilateral, Atrophy 2 [3.5] 3 [3.3] 2 [3.0] Bilateral, Interstitial Cell, Hyperplasia, Focal 2 [1.5] Germinal Epithelium, Atrophy 2 [2.5] 3 [3.3] 1 [3.0] 1 [3.0] Interstitial Cell, Hyperplasia 2 [1.5] 1 [1.0] 1 [2.0] Interstitial Cell, Hyperplasia, Focal 1 [1.0] 4 [1.5] 4 [1.5] 9 [1.6] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (47) (50) Fibrosis 1 [3.0] Hyperplasia 1 [3.0] Hyperplasia, Focal, Histiocytic 1 [3.0] 1 [2.0] Myeloid Cell, Hyperplasia 1 [3.0] 5 [3.0] Lymph Node (39) (49) (42) (38) Hemorrhage 1 [2.0] Hyperplasia, Lymphoid 1 [3.0] Mediastinal, Angiectasis 1 [3.0] Mediastinal, Congestion 1 [4.0] Mediastinal, Ectasia 1 [3.0] 3 [3.0] 1 [3.0] Mediastinal, Hemorrhage 1 [3.0] 1 [3.0] 5 [3.0] 1 [3.0] Mediastinal, Hyperplasia, Histiocytic 2 [2.5] 1 [3.0] 4 [2.8] Mediastinal, Hyperplasia, Lymphoid 1 [3.0] 1 [1.0] 1 [3.0] 1 [3.0] Mediastinal, Pigmentation 1 [3.0] 1 [3.0] Pancreatic, Angiectasis 1 [3.0] 1 [3.0] Pancreatic, Ectasia 1 [3.0] 3 [3.0] 3 [2.7] 2 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 14 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Pancreatic, Hemorrhage 1 [3.0] 1 [2.0] 4 [2.8] Pancreatic, Hyperplasia, Focal, Histiocytic 1 [3.0] Pancreatic, Hyperplasia, Histiocytic 13 [2.8] 12 [3.0] 15 [2.9] 19 [2.9] Pancreatic, Hyperplasia, Lymphoid 1 [3.0] 1 [2.0] Pancreatic, Pigmentation 1 [3.0] 1 [2.0] Lymph Node, Mandibular (2) (1) (2) (2) Hyperplasia, Plasma Cell 1 [4.0] Lymph Node, Mesenteric (47) (50) (50) (50) Ectasia 2 [2.5] 2 [3.0] Hemorrhage 1 [3.0] 1 [3.0] Hyperplasia, Histiocytic 1 [3.0] 2 [3.0] 1 [3.0] 4 [2.8] Hyperplasia, Lymphoid 2 [3.0] 1 [3.0] Spleen (49) (49) (50) (50) Angiectasis, Focal 1 [3.0] 1 [2.0] Congestion 1 [3.0] Cyst 1 Fibrosis, Focal 2 [2.5] 2 [2.5] 1 [2.0] Hematopoietic Cell Proliferation 4 [2.5] 4 [2.5] 1 [3.0] 6 [2.5] Hemorrhage 1 [3.0] Hemorrhage, Focal 1 [3.0] Hyperplasia, Lymphoid 1 [2.0] 2 [2.5] Infarct 1 [2.5] 1 [3.0] Inflammation, Granulomatous 2 [3.0] 3 [1.7] Necrosis, Focal 1 [4.0] 1 [2.0] 1 [3.0] Pigmentation 1 [2.0] Capsule, Fibrosis, Focal 1 [2.0] Thymus (48) (48) (44) (49) Atrophy 1 [3.0] 1 [3.0] Cyst, Multiple 1 [4.0] Hemorrhage 1 [3.0] 1 [2.0] Hyperplasia, Lymphoid 2 [3.0] 1 [3.0] 1 [3.0] Epithelial Cell, Cyst, Multiple 1 [3.0] Epithelial Cell, Hyperplasia 1 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (48) (47) (45) (42) Dilatation 7 [2.1] 1 [2.0] 3 [2.3] 2 [2.5] Ectasia 1 [3.0] Hyperplasia 2 [2.0] Hyperplasia, Cystic 1 [3.0] Epithelium, Pigmentation 1 [2.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 15 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM - CONT Skin (50) (50) (50) (50) Angiectasis, Focal 1 [1.0] Cyst Epithelial Inclusion 1 [1.0] 1 [3.0] Fibrosis, Focal 1 [3.0] Hemorrhage, Focal 1 [2.0] 1 [2.0] Inflammation, Chronic, Focal 1 [2.0] 1 [2.0] 1 [2.0] Necrosis, Focal 1 [2.0] Pinna, Necrosis, Focal 1 [3.0] Subcutaneous Tissue, Angiectasis, Focal 1 [2.0] Subcutaneous Tissue, Cyst 1 [2.0] Subcutaneous Tissue, Foreign Body 1 [3.0] Subcutaneous Tissue, Hemorrhage, Focal 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Skeletal Muscle (2) (1) (1) (4) Fibrosis, Focal 1 [1.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Compression, Focal 4 [3.0] 2 [2.5] 4 [3.0] 1 [2.0] Hemorrhage, Focal 2 [2.5] 3 [3.3] 2 [3.0] 1 [2.0] Necrosis, Focal 1 [3.0] 1 [3.0] Spinal Cord (1) (1) Hemorrhage, Focal 1 [3.0] Mineralization, Focal 1 [2.0] Necrosis, Focal 1 [3.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Larynx (1) (1) Glands, Hyperplasia, Focal 1 [3.0] Lung (50) (50) (50) (50) Congestion 1 [3.0] 1 [3.0] 1 [2.0] Hemorrhage, Focal 1 [2.0] 1 [3.0] 1 [2.0] Hyperplasia, Focal, Histiocytic 4 [2.3] 1 [2.0] Hyperplasia, Histiocytic 3 [1.3] 3 [1.7] 2 [1.0] 2 [1.0] Infiltration Cellular, Focal, Mixed Cell 1 [3.0] Infiltration Cellular, Mixed Cell 2 [2.5] 1 [2.0] 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 16 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Inflammation, Focal 1 [3.0] Metaplasia, Focal, Osseous 2 [1.5] 1 [1.0] 2 [1.0] Metaplasia, Osseous 2 [1.0] Alveolar Epithelium, Hyperplasia, Focal 2 [1.0] 9 [1.6] 6 [1.7] 5 [1.8] Alveolus, Foreign Body, Focal 1 [2.0] Interstitium, Edema 1 [2.0] 1 [2.0] Nose (50) (50) (50) (50) Foreign Body 1 [2.0] Inflammation, Suppurative 2 [2.0] 1 [2.0] Nasolacrimal Duct, Inflammation 2 [2.0] 1 [3.0] 2 [3.0] Nasolacrimal Duct, Inflammation, Chronic 1 [2.0] Nasolacrimal Duct, Inflammation, Suppurative 3 [2.3] Sinus, Foreign Body 1 [3.0] Sinus, Inflammation, Suppurative 1 [3.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (49) (50) (46) (50) Atrophy 1 [3.0] Cataract 1 [3.0] 1 [2.0] Synechia 1 [3.0] Cornea, Inflammation, Focal 1 [2.0] Cornea, Necrosis, Focal 1 [1.0] Iris, Hyperplasia 1 [2.0] Lens, Cataract 1 [2.0] Retina, Degeneration 1 [3.0] Retrobulbar, Inflammation, Focal 1 [2.0] Harderian Gland (50) (50) (49) (50) Hyperplasia, Focal 1 [1.0] 2 [1.0] Hyperplasia, Focal, Histiocytic 1 [1.0] Hyperplasia, Histiocytic 1 [2.0] Inflammation, Chronic, Focal 1 [1.0] 2 [1.0] 3 [1.7] Inflammation, Focal, Granulomatous 1 [1.0] Epithelium, Hyperplasia, Focal 3 [1.3] 1 [3.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (49) (49) (49) (50) Accumulation, Hyaline Droplet 1 [3.0] Atrophy, Focal 1 [2.0] Congestion 1 [2.0] 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 17 NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/14/03 Route: DOSED FEED 2-METHYLIMIDAZOLE Time: 10:45:10 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Cyst 2 [2.5] 2 [2.0] Fibrosis, Focal 1 [2.0] Infarct 1 [3.0] Inflammation 1 [2.0] Nephropathy 43 [1.3] 43 [1.3] 41 [1.2] 46 [1.2] Pelvis, Inflammation, Chronic 1 [3.0] Pelvis, Transitional Epithelium, Hyperplasia 1 [3.0] Renal Tubule, Accumulation, Hyaline Droplet 1 [3.0] 1 [1.0] 3 [3.0] 2 [3.0] Renal Tubule, Necrosis, Focal 1 [2.0] Renal Tubule, Pigmentation 5 [2.8] 3 [2.0] 2 [2.5] 3 [2.3] Urinary Bladder (50) (50) (49) (50) Hemorrhage 1 [3.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 18 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------