TDMS Study 88122-06 Pathology Tables
NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 FINAL/RATS Facility: Battelle Columbus Laboratory Chemical CAS #: 37319-17-8 Lock Date: 06/01/00 Cage Range: All Reasons For Removal: All Removal Date Range: All Treatment Groups: Include All a Number of animals examined microscopically at site and number of animals with lesion Page 1 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 13 10 9 6 Moribund Sacrifice 6 8 11 11 Dosing Accident 1 2 5 Accidently Killed 1 1 Survivors Natural Death 1 Terminal Sacrifice 30 31 28 26 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Muscularis, Inflammation, Chronic 1 (2%) Intestine Large, Colon (50) (50) (50) (50) Parasite Metazoan 2 (4%) 3 (6%) 3 (6%) 3 (6%) Intestine Large, Rectum (46) (43) (44) (42) Infiltration Cellular, Histiocyte 18 (43%) Inflammation, Acute, Focal 1 (2%) Inflammation, Chronic 1 (2%) 1 (2%) Myxomatous Change 1 (2%) 12 (27%) 35 (83%) Parasite Metazoan 2 (4%) 3 (7%) 1 (2%) Intestine Small, Jejunum (50) (50) (50) (50) Peyer's Patch, Hyperplasia, Lymphoid 1 (2%) Intestine Small, Ileum (50) (50) (50) (50) Parasite Metazoan 1 (2%) Liver (50) (50) (50) (50) Angiectasis 2 (4%) 1 (2%) Basophilic Focus 39 (78%) 35 (70%) 40 (80%) 34 (68%) Clear Cell Focus 8 (16%) 4 (8%) 8 (16%) 6 (12%) Eosinophilic Focus 12 (24%) 12 (24%) 14 (28%) 10 (20%) Fibrosis, Focal 1 (2%) Hepatodiaphragmatic Nodule 9 (18%) 8 (16%) 11 (22%) 14 (28%) Inflammation, Granulomatous 36 (72%) 31 (62%) 37 (74%) 39 (78%) Mixed Cell Focus 19 (38%) 12 (24%) 10 (20%) 9 (18%) Necrosis, Focal 1 (2%) Regeneration 1 (2%) 1 (2%) Tension Lipidosis 1 (2%) Bile Duct, Hyperplasia 13 (26%) 14 (28%) 11 (22%) 14 (28%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Bile Duct, Inflammation 1 (2%) Centrilobular, Fatty Change 1 (2%) 2 (4%) Mesentery (8) (4) (6) (9) Fat, Necrosis 7 (88%) 4 (100%) 6 (100%) 9 (100%) Oral Mucosa (1) (1) Cyst 1 (100%) Pharyngeal, Hyperplasia, Squamous 1 (100%) Pancreas (50) (50) (50) (50) Acinus, Atrophy 7 (14%) 12 (24%) 11 (22%) 8 (16%) Acinus, Hyperplasia, Focal 1 (2%) 1 (2%) Salivary Glands (50) (50) (50) (50) Parotid Gland, Atrophy, Diffuse 1 (2%) Parotid Gland, Atrophy, Focal 2 (4%) 1 (2%) Parotid Gland, Hyperplasia, Focal 1 (2%) Stomach, Forestomach (50) (50) (50) (50) Inflammation, Acute 1 (2%) Inflammation, Chronic, Focal 1 (2%) Epithelium, Hyperplasia, Squamous 1 (2%) Epithelium, Inflammation, Focal, Suppurative 1 (2%) Stomach, Glandular (50) (50) (50) (50) Inflammation, Chronic, Focal 1 (2%) Mineralization 1 (2%) 1 (2%) Pigmentation, Hemosiderin 1 (2%) Ulcer 1 (2%) 3 (6%) Epithelium, Ectasia 1 (2%) Tongue (1) Epithelium, Hyperplasia, Focal, Squamous 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) Aorta, Inflammation, Chronic 1 (2%) 1 (2%) Heart (50) (50) (50) (50) Artery, Hyperplasia, Focal 1 (2%) Atrium, Thrombosis 1 (2%) Myocardium, Degeneration 38 (76%) 30 (60%) 31 (62%) 34 (68%) Myocardium, Inflammation, Chronic, Focal 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hyperplasia, Focal 20 (40%) 17 (34%) 17 (34%) 19 (38%) Adrenal Medulla (50) (50) (50) (50) Hyperplasia, Focal 5 (10%) 2 (4%) 4 (8%) 4 (8%) Necrosis 1 (2%) Islets, Pancreatic (50) (50) (50) (50) Hyperplasia 1 (2%) 1 (2%) 1 (2%) Pituitary Gland (50) (50) (50) (50) Angiectasis 1 (2%) 2 (4%) 2 (4%) 2 (4%) Cyst 20 (40%) 21 (42%) 18 (36%) 22 (44%) Hemorrhage 1 (2%) Pars Distalis, Hyperplasia, Focal 16 (32%) 15 (30%) 10 (20%) 13 (26%) Pars Distalis, Mineralization 1 (2%) Thyroid Gland (50) (50) (50) (50) Hemorrhage 1 (2%) 1 (2%) C-Cell, Hyperplasia 33 (66%) 38 (76%) 34 (68%) 31 (62%) Follicle, Hyperplasia 2 (4%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (50) (50) (49) Cyst 4 (8%) 4 (8%) 4 (8%) 3 (6%) Fibrosis 1 (2%) Hyperplasia 1 (2%) Hyperplasia, Focal 5 (10%) 3 (6%) 2 (4%) 3 (6%) Inflammation, Chronic 7 (14%) 10 (20%) 11 (22%) 8 (16%) Inflammation, Suppurative 1 (2%) 1 (2%) 2 (4%) Ovary (50) (50) (50) (50) Cyst 4 (8%) 5 (10%) 7 (14%) 5 (10%) Inflammation, Granulomatous 1 (2%) Oviduct (1) Cyst 1 (100%) Uterus (50) (50) (50) (50) Inflammation, Suppurative 1 (2%) Ulcer 1 (2%) Cervix, Endometrium, Hyperplasia 1 (2%) Endometrium, Hyperplasia, Cystic 4 (8%) 5 (10%) 3 (6%) 6 (12%) Endometrium, Inflammation, Chronic 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Vagina (2) (2) Hyperplasia 1 (50%) Infiltration Cellular, Polymorphonuclear 1 (50%) Epithelium, Vacuolization Cytoplasmic 1 (50%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Fibrosis 1 (2%) 1 (2%) Lymph Node (7) (19) (14) (13) Deep Cervical, Hemorrhage 1 (8%) Deep Cervical, Hyperplasia, Lymphoid 1 (5%) 1 (8%) Deep Cervical, Infiltration Cellular, Histiocyte 1 (14%) Mediastinal, Congestion 1 (8%) Mediastinal, Ectasia 2 (11%) 3 (21%) 1 (8%) Mediastinal, Hemorrhage 3 (16%) 2 (14%) 3 (23%) Mediastinal, Hyperplasia, Lymphoid 2 (29%) 3 (16%) 3 (21%) 6 (46%) Mediastinal, Infiltration Cellular, Mast Cell 1 (8%) Mediastinal, Infiltration Cellular, Plasma Cell 1 (14%) 1 (8%) Mediastinal, Infiltration Cellular, Histiocyte 1 (14%) 4 (29%) Mediastinal, Necrosis, Lymphoid 1 (5%) Pancreatic, Infiltration Cellular, Histiocyte 1 (8%) Pancreatic, Pigmentation, Hemosiderin 1 (8%) Lymph Node, Mandibular (3) (8) (3) (2) Infiltration Cellular, Histiocyte 1 (13%) Necrosis, Lymphoid 1 (13%) Lymph Node, Mesenteric (50) (50) (50) (49) Ectasia 1 (2%) Hyperplasia, Lymphoid 2 (4%) 2 (4%) Infiltration Cellular, Histiocyte 3 (6%) 27 (54%) 42 (86%) Spleen (50) (50) (50) (50) Hematopoietic Cell Proliferation 6 (12%) 2 (4%) 4 (8%) 5 (10%) Hemorrhage 1 (2%) Hyperplasia, Lymphohistiocytic 1 (2%) 2 (4%) 4 (8%) Necrosis, Focal 1 (2%) Lymphoid Follicle, Atrophy 35 (70%) 32 (64%) 31 (62%) 28 (56%) Lymphoid Follicle, Hyperplasia 1 (2%) Thymus (45) (41) (46) (41) Epithelial Cell, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) Hyperplasia 2 (4%) Hyperplasia, Focal 6 (12%) 3 (6%) 3 (6%) 2 (4%) Duct, Dilatation 29 (58%) 15 (30%) 20 (40%) 23 (46%) Skin (50) (50) (50) (50) Ulcer 1 (2%) Subcutaneous Tissue, Pigmentation, Hemosiderin 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Osteopetrosis 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Hydrocephalus 8 (16%) 6 (12%) 8 (16%) 10 (20%) Cerebrum, Degeneration, Focal 1 (2%) Cerebrum, Gliosis, Focal 1 (2%) Cerebrum, Necrosis, Focal 1 (2%) Hypothalamus, Compression 5 (10%) 3 (6%) 5 (10%) 8 (16%) Medulla, Compression 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 5 (10%) 3 (6%) 1 (2%) Hemorrhage 2 (4%) 1 (2%) 1 (2%) 4 (8%) Infiltration Cellular, Histiocyte 1 (2%) Inflammation, Chronic Active, Focal 1 (2%) Inflammation, Granulomatous, Multifocal 1 (2%) Metaplasia, Osseous 2 (4%) 1 (2%) 1 (2%) Alveolar Epithelium, Hyperplasia 1 (2%) Alveolar Epithelium, Hyperplasia, Focal 3 (6%) 4 (8%) 5 (10%) 3 (6%) Alveolus, Emphysema, Focal 1 (2%) Alveolus, Inflammation, Acute 1 (2%) 1 (2%) Alveolus, Inflammation, Chronic Active, Focal 2 (4%) 25 (50%) 27 (54%) 34 (68%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 28 MG/KG 84 MG/KG 252 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Nose (50) (50) (50) (50) Inflammation, Chronic 6 (12%) 3 (6%) 7 (14%) 5 (10%) Trachea (50) (50) (50) (50) Hemorrhage 1 (2%) Inflammation, Chronic 1 (2%) Peritracheal Tissue, Hemorrhage 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (3) (1) (3) Cataract 1 (33%) 1 (100%) 2 (67%) Degeneration 2 (67%) Cornea, Fibrosis 1 (33%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Infarct 2 (4%) 1 (2%) Inflammation, Focal, Suppurative 1 (2%) Nephropathy 16 (32%) 13 (26%) 11 (22%) 16 (32%) Pelvis, Inflammation, Suppurative 1 (2%) Renal Tubule, Cyst 1 (2%) Renal Tubule, Necrosis 1 (2%) Renal Tubule, Pigmentation, Lipofuscin 1 (2%) Urinary Bladder (50) (50) (50) (50) Hemorrhage 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 7 9 8 5 Moribund Sacrifice 15 10 17 12 Dosing Accident 2 2 5 Survivors Terminal Sacrifice 26 29 25 28 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Muscularis, Periesophageal Tissue, Inflammation, Chronic 1 (2%) Periesophageal Tissue, Hemorrhage 1 (2%) 1 (2%) Intestine Large, Colon (50) (50) (50) (50) Parasite Metazoan 4 (8%) 1 (2%) 3 (6%) Intestine Large, Rectum (48) (48) (49) (45) Erosion 2 (4%) 2 (4%) Infiltration Cellular, Histiocyte 4 (9%) Inflammation, Chronic 1 (2%) 1 (2%) 5 (11%) Myxomatous Change 1 (2%) 3 (6%) 25 (56%) Parasite Metazoan 5 (10%) 8 (17%) 4 (8%) 3 (7%) Ulcer 1 (2%) Intestine Small, Duodenum (50) (50) (50) (50) Epithelium, Cyst 1 (2%) Epithelium, Necrosis 1 (2%) Intestine Small, Jejunum (50) (50) (50) (50) Inflammation, Chronic, Focal 1 (2%) Peyer's Patch, Hyperplasia 1 (2%) Intestine Small, Ileum (50) (50) (50) (50) Parasite Metazoan 1 (2%) Liver (50) (50) (50) (50) Angiectasis 1 (2%) Basophilic Focus 27 (54%) 27 (54%) 22 (44%) 19 (38%) Clear Cell Focus 18 (36%) 22 (44%) 23 (46%) 16 (32%) Eosinophilic Focus 9 (18%) 12 (24%) 5 (10%) 4 (8%) Fatty Change, Focal 1 (2%) Fibrosis, Focal 1 (2%) 1 (2%) 1 (2%) Hepatodiaphragmatic Nodule 5 (10%) 5 (10%) 7 (14%) 9 (18%) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Inflammation, Granulomatous 30 (60%) 26 (52%) 32 (64%) 27 (54%) Mixed Cell Focus 8 (16%) 17 (34%) 13 (26%) 11 (22%) Necrosis, Focal 1 (2%) Artery, Hyperplasia, Focal 1 (2%) Bile Duct, Hyperplasia 44 (88%) 41 (82%) 32 (64%) 39 (78%) Centrilobular, Degeneration 1 (2%) 1 (2%) 1 (2%) 1 (2%) Centrilobular, Fatty Change 1 (2%) 1 (2%) Centrilobular, Necrosis 1 (2%) 1 (2%) 2 (4%) 3 (6%) Mesentery (9) (11) (9) (13) Accessory Spleen 1 (8%) Hemorrhage 1 (8%) Fat, Inflammation, Granulomatous 2 (15%) Fat, Necrosis 7 (78%) 10 (91%) 9 (100%) 8 (62%) Pancreas (50) (50) (50) (50) Fibrosis 1 (2%) Acinus, Atrophy 12 (24%) 14 (28%) 14 (28%) 16 (32%) Acinus, Hyperplasia, Focal 2 (4%) 1 (2%) Duct, Necrosis 1 (2%) Salivary Glands (50) (50) (49) (50) Duct, Parotid Gland, Sublingual Gland, Mineralization 1 (2%) Parotid Gland, Atrophy, Focal 1 (2%) 1 (2%) Sublingual Gland, Atrophy, Focal 1 (2%) Sublingual Gland, Hypertrophy, Focal 1 (2%) Stomach, Forestomach (50) (50) (50) (50) Edema 1 (2%) Hyperplasia, Focal, Squamous 2 (4%) 1 (2%) Inflammation, Acute 1 (2%) Inflammation, Chronic 1 (2%) Mineralization 1 (2%) Ulcer 1 (2%) 2 (4%) 4 (8%) 1 (2%) Stomach, Glandular (50) (50) (50) (50) Mineralization 2 (4%) 1 (2%) 1 (2%) Ulcer 1 (2%) 3 (6%) 5 (10%) 2 (4%) Epithelium, Hyperplasia, Focal 1 (2%) 2 (4%) 1 (2%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) Aorta, Mineralization 1 (2%) Heart (50) (50) (50) (50) Atrium, Inflammation, Chronic 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM - CONT Atrium, Thrombosis 2 (4%) 4 (8%) 1 (2%) Myocardium, Degeneration 41 (82%) 41 (82%) 42 (84%) 41 (82%) Myocardium, Necrosis, Focal 1 (2%) Vein, Thrombosis 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Hyperplasia 1 (2%) Hyperplasia, Diffuse 1 (2%) Hyperplasia, Focal 14 (28%) 16 (32%) 17 (34%) 17 (34%) Necrosis, Acute 1 (2%) Necrosis, Focal 1 (2%) Adrenal Medulla (50) (50) (50) (50) Fibrosis 3 (6%) Hyperplasia, Diffuse 2 (4%) Hyperplasia, Focal 10 (20%) 17 (34%) 12 (24%) 13 (26%) Necrosis, Acute 1 (2%) Necrosis, Focal 1 (2%) Islets, Pancreatic (50) (50) (50) (50) Hyperplasia 1 (2%) 1 (2%) 1 (2%) 2 (4%) Parathyroid Gland (46) (44) (45) (47) Cyst, Multiple 1 (2%) Pituitary Gland (50) (50) (50) (50) Angiectasis 1 (2%) 1 (2%) Cyst 3 (6%) 3 (6%) 5 (10%) 2 (4%) Hyperplasia 2 (4%) Necrosis, Focal 1 (2%) Pars Distalis, Hyperplasia, Focal 12 (24%) 12 (24%) 17 (34%) 9 (18%) Thyroid Gland (50) (50) (50) (50) C-Cell, Hyperplasia 31 (62%) 36 (72%) 40 (80%) 35 (70%) Follicle, Cyst 1 (2%) Follicle, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Peritoneum (1) Inflammation, Chronic 1 (100%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Coagulating Gland (1) (1) Inflammation, Chronic 1 (100%) Epididymis (50) (50) (50) (50) Fibrosis 1 (2%) Granuloma Sperm 1 (2%) 1 (2%) 1 (2%) Inflammation, Acute 1 (2%) Preputial Gland (50) (50) (50) (50) Cyst 3 (6%) 2 (4%) Hyperplasia 1 (2%) 2 (4%) Inflammation, Chronic 35 (70%) 44 (88%) 42 (84%) 37 (74%) Inflammation, Suppurative 1 (2%) 2 (4%) 1 (2%) Prostate, NOS (50) (50) (50) (49) Hyperplasia 1 (2%) Hyperplasia, Focal 1 (2%) Inflammation, Acute 1 (2%) Inflammation, Chronic Active 18 (36%) 16 (32%) 19 (38%) 18 (37%) Seminal Vesicle (50) (50) (50) (49) Atrophy 1 (2%) 1 (2%) Fibrosis 1 (2%) 1 (2%) Hyperplasia 4 (8%) 2 (4%) 2 (4%) Testes (50) (50) (50) (50) Cyst 2 (4%) Artery, Necrosis 1 (2%) Germinal Epithelium, Atrophy 3 (6%) 1 (2%) 1 (2%) 1 (2%) Interstitial Cell, Hyperplasia 5 (10%) 1 (2%) 2 (4%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Fibrosis 2 (4%) 1 (2%) 1 (2%) Infiltration Cellular, Lymphocyte 1 (2%) Infiltration Cellular, Histiocyte 1 (2%) Lymph Node (11) (17) (10) (13) Deep Cervical, Angiectasis 1 (8%) Deep Cervical, Hyperplasia, Lymphoid 1 (9%) Mediastinal, Angiectasis 1 (8%) Mediastinal, Ectasia 2 (12%) 2 (20%) 1 (8%) Mediastinal, Hemorrhage 2 (18%) 1 (8%) Mediastinal, Hyperplasia, Lymphoid 2 (18%) 7 (41%) 2 (20%) 1 (8%) Mediastinal, Hyperplasia, Plasma Cell 1 (8%) Mediastinal, Infiltration Cellular, a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Histiocyte 1 (10%) Pancreatic, Ectasia 1 (6%) Pancreatic, Hemorrhage 1 (6%) Renal, Ectasia 1 (10%) Renal, Infiltration Cellular, Plasma Cell 1 (10%) Lymph Node, Mandibular (5) (5) (9) (2) Ectasia 1 (11%) 1 (50%) Infiltration Cellular, Plasma Cell 1 (20%) Lymph Node, Mesenteric (50) (50) (50) (49) Ectasia 2 (4%) 2 (4%) Fibrosis 1 (2%) Hemorrhage 1 (2%) 1 (2%) 1 (2%) Hyperplasia, Lymphoid 1 (2%) 1 (2%) 1 (2%) Infiltration Cellular, Histiocyte 1 (2%) 1 (2%) 18 (36%) 39 (80%) Inflammation, Granulomatous 3 (6%) Necrosis, Lymphoid 1 (2%) Endothelial Cell, Hyperplasia 1 (2%) Spleen (50) (50) (50) (50) Fibrosis, Focal 2 (4%) 1 (2%) Hematopoietic Cell Proliferation 2 (4%) 2 (4%) 3 (6%) 4 (8%) Hyperplasia, Lymphohistiocytic 2 (4%) 2 (4%) 2 (4%) 8 (16%) Necrosis, Focal 1 (2%) Capsule, Fibrosis, Focal 1 (2%) 1 (2%) Lymphoid Follicle, Atrophy 20 (40%) 25 (50%) 29 (58%) 25 (50%) Lymphoid Follicle, Hyperplasia 1 (2%) 1 (2%) 1 (2%) Lymphoid Follicle, Necrosis 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (49) (49) (50) (48) Hyperplasia 25 (51%) 37 (76%) 31 (62%) 17 (35%) Duct, Dilatation 12 (24%) 24 (49%) 27 (54%) 15 (31%) Duct, Dilatation, Diffuse 1 (2%) Skin (50) (50) (50) (50) Metaplasia, Osseous 1 (2%) Epidermis, Cyst, Squamous 1 (2%) Epidermis, Epidermis, Cyst 1 (2%) Sebaceous Gland, Hyperplasia, Focal 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM a Number of animals examined microscopically at site and number of animals with lesion Page 12 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM - CONT Bone (50) (50) (50) (50) Cyst 2 (4%) Femur, Hyperostosis 1 (2%) Skeletal Muscle (1) (2) Hemorrhage 1 (50%) Inflammation, Acute 1 (50%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Hydrocephalus 8 (16%) 7 (14%) 9 (18%) 6 (12%) Cerebrum, Degeneration, Focal 1 (2%) Hippocampus, Cerebrum, Degeneration 1 (2%) Hypothalamus, Compression 6 (12%) 2 (4%) 5 (10%) 4 (8%) Medulla, Degeneration, Focal 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Larynx (1) Hemorrhage 1 (100%) Lung (50) (50) (50) (50) Emphysema, Focal 1 (2%) Hemorrhage 2 (4%) 1 (2%) 1 (2%) 4 (8%) Infiltration Cellular, Histiocyte 1 (2%) Metaplasia, Osseous 3 (6%) Myxomatous Change 1 (2%) Thrombosis 1 (2%) Alveolar Epithelium, Hyperplasia 6 (12%) 1 (2%) Alveolar Epithelium, Hyperplasia, Focal 3 (6%) 4 (8%) 3 (6%) 3 (6%) Alveolar Epithelium, Metaplasia, Squamous 2 (4%) Alveolus, Emphysema, Focal 1 (2%) 1 (2%) Alveolus, Inflammation, Acute 1 (2%) 1 (2%) 2 (4%) Alveolus, Inflammation, Chronic Active, Focal 6 (12%) 11 (22%) 14 (28%) Artery, Thrombosis 1 (2%) Interstitium, Fibrosis, Focal 1 (2%) Interstitium, Alveolus, Inflammation 1 (2%) Mediastinum, Inflammation, Chronic 1 (2%) Nose (50) (50) (50) (50) Foreign Body 1 (2%) Inflammation, Chronic 9 (18%) 7 (14%) 8 (16%) 9 (18%) Thrombosis 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 13 NTP Experiment-Test: 88122-06 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ELMIRON Date: 09/26/01 Route: GAVAGE Time: 14:32:26 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 14 MG/KG 42 MG/KG 126 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Ulcer 2 (4%) 1 (2%) Trachea (50) (50) (50) (50) Hemorrhage 1 (2%) Inflammation, Chronic 1 (2%) 4 (8%) Ulcer 1 (2%) Epithelium, Metaplasia, Squamous 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (1) (1) Cataract 1 (100%) 1 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Glomerulosclerosis 1 (2%) Hemorrhage 1 (2%) Hydronephrosis 2 (4%) Infarct 2 (4%) 2 (4%) Nephropathy 40 (80%) 42 (84%) 41 (82%) 37 (74%) Artery, Thrombosis 1 (2%) Pelvis, Inflammation, Suppurative 1 (2%) Renal Tubule, Necrosis, Focal 2 (4%) 1 (2%) 2 (4%) Renal Tubule, Pigmentation, Lipofuscin 1 (2%) 3 (6%) Vein, Inflammation, Chronic 1 (2%) Urethra (1) Inflammation, Suppurative 1 (100%) Urinary Bladder (50) (50) (50) (49) Hemorrhage 1 (2%) Inflammation, Acute 1 (2%) Mineralization 1 (2%) Ulcer 2 (4%) a Number of animals examined microscopically at site and number of animals with lesion Page 14 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------