TDMS Study 05161-05 Pathology Tables
NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 RATS/FINAL#1 Facility: Southern Research Institute Chemical CAS #: 23246-96-0 Lock Date: 11/17/99 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: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 50 50 Early Deaths Natural Death 6 11 6 12 2 31 Dosing Accident 2 6 3 2 3 Moribund Sacrifice 9 11 13 14 16 19 Survivors Terminal Sacrifice 33 22 28 22 29 Animals Examined Microscopically 50 50 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (48) (50) (48) (50) (49) (50) Inflammation, Chronic 2 (4%) Perforation 1 (2%) Intestine Large, Colon (49) (50) (50) (47) (50) (50) Diverticulum 1 (2%) Intestine Large, Cecum (50) (50) (48) (47) (50) (50) Edema 1 (2%) Liver (50) (50) (50) (50) (50) (50) Angiectasis 2 (4%) 1 (2%) 2 (4%) 5 (10%) 1 (2%) Basophilic Focus 45 (90%) 46 (92%) 44 (88%) 42 (84%) 40 (80%) 20 (40%) Clear Cell Focus 9 (18%) 8 (16%) 9 (18%) 13 (26%) 22 (44%) 2 (4%) Cyst 1 (2%) Degeneration, Cystic 1 (2%) 1 (2%) Eosinophilic Focus 1 (2%) 2 (4%) 6 (12%) 4 (8%) 12 (24%) 13 (26%) Hematopoietic Cell Proliferation 2 (4%) 1 (2%) 4 (8%) 1 (2%) 3 (6%) Hemorrhage 2 (4%) 1 (2%) 7 (14%) Hepatodiaphragmatic Nodule 13 (26%) 8 (16%) 9 (18%) 6 (12%) 4 (8%) 5 (10%) Infiltration Cellular, Mixed Cell 9 (18%) 7 (14%) 9 (18%) 8 (16%) 15 (30%) 3 (6%) Mixed Cell Focus 8 (16%) 10 (20%) 10 (20%) 11 (22%) 23 (46%) 5 (10%) Necrosis, Focal 4 (8%) 2 (4%) 3 (6%) 4 (8%) 4 (8%) 15 (30%) Bile Duct, Hyperplasia 2 (4%) 1 (2%) 4 (8%) 4 (8%) 3 (6%) 10 (20%) Hepatocyte, Cytomegaly 7 (14%) 23 (46%) 32 (64%) 29 (58%) Hepatocyte, Hyperplasia, Atypical 1 (2%) Hepatocyte, Hyperplasia, Focal 1 (2%) Hepatocyte, Hyperplasia, Regenerative 8 (16%) 50 (100%) Hepatocyte, Vacuolization Cytoplasmic 4 (8%) 5 (10%) 7 (14%) 4 (8%) 3 (6%) 5 (10%) Kupffer Cell, Pigmentation 2 (4%) 3 (6%) 2 (4%) 6 (12%) 4 (8%) Mesentery (10) (10) (18) (14) (13) (5) Accessory Spleen 2 (20%) 1 (6%) 2 (14%) 1 (8%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Fat, Necrosis 8 (80%) 10 (100%) 18 (100%) 12 (86%) 9 (69%) 3 (60%) Pancreas (50) (50) (50) (46) (50) (50) Atrophy 10 (20%) 3 (6%) 9 (18%) 8 (17%) 4 (8%) 4 (8%) Acinus, Hyperplasia, Focal 3 (6%) 1 (2%) 1 (2%) Salivary Glands (50) (50) (50) (50) (50) (50) Atrophy 1 (2%) 2 (4%) Stomach, Forestomach (50) (50) (50) (49) (49) (50) Ulcer 2 (4%) Epithelium, Hyperplasia 1 (2%) 5 (10%) 1 (2%) 1 (2%) 3 (6%) Stomach, Glandular (50) (50) (50) (49) (49) (50) Erosion 2 (4%) 1 (2%) 9 (18%) Hemorrhage 1 (2%) Mineralization 1 (2%) Ulcer 2 (4%) 7 (14%) Tooth (1) Malformation 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) (50) (50) Cardiomyopathy 12 (24%) 15 (30%) 8 (16%) 13 (26%) 8 (16%) 6 (12%) Thrombosis 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 6 (12%) 2 (4%) 6 (12%) 4 (8%) 2 (4%) 7 (14%) Atrophy 1 (2%) Degeneration, Fatty 9 (18%) 9 (18%) 12 (24%) 8 (16%) 13 (26%) 3 (6%) Hyperplasia, Diffuse 3 (6%) 1 (2%) Hyperplasia, Focal 4 (8%) 5 (10%) 6 (12%) 4 (8%) 9 (18%) 3 (6%) Hypertrophy 1 (2%) 1 (2%) Hypertrophy, Focal 9 (18%) 5 (10%) 7 (14%) 2 (4%) 4 (8%) 2 (4%) Necrosis 1 (2%) Adrenal Medulla (50) (49) (50) (50) (50) (50) Hyperplasia 1 (2%) 3 (6%) 3 (6%) 3 (6%) Pituitary Gland (50) (48) (50) (49) (50) (49) Pars Distalis, Angiectasis 6 (12%) 6 (13%) 8 (16%) 8 (16%) 9 (18%) 7 (14%) Pars Distalis, Cyst 16 (32%) 11 (23%) 19 (38%) 16 (33%) 17 (34%) 19 (39%) Pars Distalis, Hyperplasia 1 (2%) 1 (2%) Pars Distalis, Hyperplasia, Focal 10 (20%) 8 (17%) 9 (18%) 11 (22%) 7 (14%) 6 (12%) a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Pars Intermedia, Angiectasis 1 (2%) 1 (2%) 1 (2%) Pars Intermedia, Cyst 1 (2%) 1 (2%) Thyroid Gland (49) (50) (49) (49) (50) (50) Ultimobranchial Cyst 1 (2%) 2 (4%) 1 (2%) 2 (4%) C-Cell, Hyperplasia 22 (45%) 9 (18%) 24 (49%) 15 (31%) 20 (40%) 10 (20%) Follicle, Cyst 1 (2%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (49) (49) (49) (48) (49) (50) Cyst 5 (10%) 2 (4%) 3 (6%) 1 (2%) 4 (8%) 3 (6%) Hyperplasia 3 (6%) 5 (10%) 4 (8%) 2 (4%) 2 (4%) Inflammation, Chronic 4 (8%) 5 (10%) 4 (8%) 3 (6%) 4 (8%) Ovary (50) (49) (50) (50) (50) (50) Cyst 11 (22%) 7 (14%) 8 (16%) 9 (18%) 6 (12%) 9 (18%) Infiltration Cellular, Mixed Cell 1 (2%) Uterus (50) (50) (50) (50) (50) (50) Hydrometra 5 (10%) 7 (14%) 6 (12%) 6 (12%) 6 (12%) Hyperplasia, Cystic 4 (8%) 3 (6%) 7 (14%) 5 (10%) 2 (4%) 9 (18%) Inflammation, Chronic 2 (4%) 1 (2%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) (50) (50) Hyperplasia 6 (12%) 3 (6%) 8 (16%) 7 (14%) 10 (20%) 32 (64%) Inflammation, Granulomatous 1 (2%) Myelofibrosis 1 (2%) 1 (2%) 1 (2%) 1 (2%) Lymph Node (26) (24) (36) (19) (21) (40) Iliac, Pigmentation 1 (4%) Mediastinal, Congestion 4 (15%) 3 (13%) 3 (8%) 3 (16%) 1 (5%) 9 (23%) Mediastinal, Hemorrhage 5 (19%) 8 (33%) 9 (25%) 5 (26%) 7 (33%) 25 (63%) Mediastinal, Infiltration Cellular, Histiocyte 1 (4%) Mediastinal, Pigmentation 23 (88%) 22 (92%) 32 (89%) 15 (79%) 16 (76%) 31 (78%) Pancreatic, Hemorrhage 2 (5%) Pancreatic, Hyperplasia, Histiocytic 1 (4%) 1 (3%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Pancreatic, Hyperplasia, Lymphoid 1 (4%) 1 (4%) 1 (3%) 1 (5%) Pancreatic, Pigmentation 1 (4%) 2 (6%) 4 (19%) 1 (3%) Renal, Pigmentation 2 (6%) 2 (10%) 1 (3%) Lymph Node, Mandibular (50) (49) (48) (50) (50) (50) Ectasia 3 (6%) Hemorrhage 1 (2%) 1 (2%) 1 (2%) 1 (2%) Hyperplasia, Lymphoid 2 (4%) 3 (6%) 1 (2%) 5 (10%) 5 (10%) Pigmentation 5 (10%) 2 (4%) 2 (4%) 11 (22%) 3 (6%) Lymph Node, Mesenteric (50) (50) (50) (47) (49) (49) Congestion 1 (2%) 1 (2%) Hemorrhage 1 (2%) 2 (4%) 3 (6%) 4 (9%) 6 (12%) Hyperplasia 1 (2%) Inflammation, Granulomatous 1 (2%) Pigmentation 3 (6%) 1 (2%) 2 (4%) 2 (4%) 3 (6%) 2 (4%) Spleen (50) (50) (50) (50) (50) (50) Congestion 1 (2%) 3 (6%) 7 (14%) Fibrosis 1 (2%) 1 (2%) 2 (4%) 2 (4%) Hematopoietic Cell Proliferation 24 (48%) 33 (66%) 25 (50%) 26 (52%) 27 (54%) 34 (68%) Hyperplasia, Stromal 1 (2%) Necrosis 1 (2%) Pigmentation 37 (74%) 41 (82%) 35 (70%) 34 (68%) 35 (70%) 29 (58%) Thymus (48) (48) (46) (48) (50) (49) Cyst 1 (2%) Hemorrhage 2 (4%) 2 (4%) Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) (49) (49) Hyperplasia 48 (96%) 46 (92%) 46 (92%) 45 (90%) 44 (90%) 43 (88%) Skin (50) (50) (49) (50) (50) (50) Cyst Epithelial Inclusion 1 (2%) Hemorrhage 1 (2%) Hyperkeratosis 1 (2%) Inflammation, Chronic 1 (2%) Ulcer 1 (2%) Epidermis, Hyperplasia 1 (2%) Subcutaneous Tissue, Edema 2 (4%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM - CONT Bone (50) (50) (50) (50) (50) (50) Cranium, Osteopetrosis 10 (20%) 10 (20%) 12 (24%) 6 (12%) 7 (14%) Femur, Osteopetrosis 12 (24%) 7 (14%) 9 (18%) 15 (30%) 14 (28%) 9 (18%) Skeletal Muscle (1) (1) (2) (6) Hemorrhage 4 (67%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) (50) (50) Compression 9 (18%) 11 (22%) 15 (30%) 6 (12%) 12 (24%) 2 (4%) Hemorrhage 1 (2%) 1 (2%) 3 (6%) Hydrocephalus 3 (6%) 4 (8%) 8 (16%) 1 (2%) 10 (20%) 3 (6%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) (50) (50) Congestion 4 (8%) 7 (14%) 2 (4%) 8 (16%) 1 (2%) 1 (2%) Edema 1 (2%) 2 (4%) Hemorrhage 4 (8%) 7 (14%) 1 (2%) 3 (6%) 5 (10%) 19 (38%) Infiltration Cellular, Histiocyte 46 (92%) 41 (82%) 48 (96%) 44 (88%) 49 (98%) 42 (84%) Inflammation, Chronic 1 (2%) Inflammation, Granulomatous 1 (2%) Metaplasia, Osseous 2 (4%) Alveolar Epithelium, Hyperplasia 5 (10%) 4 (8%) 10 (20%) 5 (10%) 5 (10%) 7 (14%) Nose (50) (50) (50) (49) (50) (50) Foreign Body 2 (4%) 1 (2%) 1 (2%) 1 (2%) Inflammation, Chronic 3 (6%) 2 (4%) 1 (2%) Olfactory Epithelium, Degeneration 1 (2%) 1 (2%) Respiratory Epithelium, Hyperplasia 1 (2%) 1 (2%) 3 (6%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (1) Cataract 1 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) (50) (50) Cyst 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 0.01 0.033 0.1 0.33 1.0 MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Hydronephrosis 1 (2%) 1 (2%) Infarct 1 (2%) 1 (2%) Inflammation, Chronic 1 (2%) Nephropathy 32 (64%) 32 (64%) 33 (66%) 30 (60%) 38 (76%) 28 (56%) Papilla, Fibrosis, Focal 1 (2%) Pelvis, Mineralization 1 (2%) Renal Tubule, Cytoplasmic Alteration 1 (2%) 1 (2%) Renal Tubule, Dilatation 1 (2%) 2 (4%) 2 (4%) 1 (2%) Renal Tubule, Hyaline Droplet 33 (66%) 23 (46%) 30 (60%) 26 (52%) 26 (52%) 9 (18%) Renal Tubule, Mineralization 1 (2%) Renal Tubule, Necrosis 1 (2%) 1 (2%) 6 (12%) Renal Tubule, Pigmentation 38 (76%) 28 (56%) 31 (62%) 31 (62%) 41 (82%) 23 (46%) Transitional Epithelium, Hyperplasia 1 (2%) 1 (2%) 1 (2%) 1 (2%) 5 (10%) Urinary Bladder (50) (50) (50) (48) (50) (50) Edema 1 (2%) 1 (2%) Transitional Epithelium, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 1.0 MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 Early Deaths Moribund Sacrifice 1 9 Natural Death 36 Dosing Accident 2 Survivors Terminal Sacrifice 49 3 Animals Examined Microscopically 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) Perforation 1 (2%) Intestine Large, Cecum (50) (49) Edema 1 (2%) 3 (6%) Intestine Small, Duodenum (50) (50) Hemorrhage 1 (2%) Necrosis 1 (2%) Liver (50) (50) Basophilic Focus 32 (64%) 21 (42%) Clear Cell Focus 3 (6%) 5 (10%) Degeneration, Cystic 1 (2%) 3 (6%) Eosinophilic Focus 3 (6%) 15 (30%) Hematopoietic Cell Proliferation 2 (4%) Hemorrhage 4 (8%) Hepatodiaphragmatic Nodule 4 (8%) 4 (8%) Infiltration Cellular, Mixed Cell 8 (16%) Metaplasia, Osseous 1 (2%) Mixed Cell Focus 3 (6%) 7 (14%) Necrosis, Focal 23 (46%) Bile Duct, Hyperplasia 48 (96%) 37 (74%) Hepatocyte, Cytomegaly 32 (64%) Hepatocyte, Hyperplasia, Atypical 1 (2%) Hepatocyte, Hyperplasia, Regenerative 49 (98%) Hepatocyte, Vacuolization Cytoplasmic 30 (60%) 5 (10%) Kupffer Cell, Pigmentation 1 (2%) Mesentery (8) (9) Accessory Spleen 1 (13%) 1 (11%) Fat, Necrosis 7 (88%) 3 (33%) Pancreas (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 1.0 MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Atrophy 7 (14%) 7 (14%) Acinus, Cytoplasmic Alteration 1 (2%) Acinus, Hyperplasia, Focal 1 (2%) Salivary Glands (50) (50) Atrophy 1 (2%) Necrosis 2 (4%) Stomach, Forestomach (50) (50) Edema 2 (4%) Ulcer 3 (6%) Stomach, Glandular (50) (50) Erosion 10 (20%) Hemorrhage 1 (2%) Ulcer 6 (12%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) Cardiomyopathy 32 (64%) 28 (56%) Myocardium, Hemorrhage 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (49) (50) Accessory Adrenal Cortical Nodule 8 (16%) 1 (2%) Degeneration, Fatty 5 (10%) 4 (8%) Hyperplasia, Diffuse 1 (2%) Hyperplasia, Focal 3 (6%) 1 (2%) Hypertrophy 1 (2%) Necrosis 1 (2%) Pituitary Gland (50) (49) Pars Distalis, Cyst 4 (8%) 2 (4%) Pars Distalis, Hyperplasia, Focal 5 (10%) 4 (8%) Thyroid Gland (50) (50) Ultimobranchial Cyst 1 (2%) C-Cell, Hyperplasia 4 (8%) 1 (2%) Follicle, Cyst 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 1.0 MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (50) (50) Atypia Cellular 9 (18%) 9 (18%) Preputial Gland (50) (50) Inflammation, Chronic 24 (48%) 16 (32%) Prostate (50) (50) Inflammation, Chronic 18 (36%) 15 (30%) Testes (50) (50) Atrophy 3 (6%) 6 (12%) Interstitial Cell, Hyperplasia 22 (44%) 12 (24%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (49) Hyperplasia 1 (2%) 36 (73%) Myelofibrosis 1 (2%) Lymph Node (13) (39) Bronchial, Hemorrhage 1 (3%) Bronchial, Pigmentation 1 (3%) Iliac, Necrosis 1 (3%) Mediastinal, Congestion 3 (23%) 11 (28%) Mediastinal, Hemorrhage 3 (23%) 20 (51%) Mediastinal, Hyperplasia 1 (8%) Mediastinal, Necrosis 1 (3%) Mediastinal, Pigmentation 10 (77%) 20 (51%) Pancreatic, Hemorrhage 2 (5%) Pancreatic, Pigmentation 2 (5%) Renal, Hemorrhage 3 (8%) Renal, Necrosis 1 (3%) Renal, Pigmentation 3 (8%) Lymph Node, Mandibular (50) (50) Congestion 1 (2%) Hemorrhage 2 (4%) 1 (2%) Pigmentation 1 (2%) 1 (2%) Lymph Node, Mesenteric (50) (50) Congestion 4 (8%) Hemorrhage 1 (2%) 8 (16%) Pigmentation 1 (2%) Spleen (50) (49) Congestion 24 (49%) Fibrosis 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 1.0 MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Hematopoietic Cell Proliferation 1 (2%) 23 (47%) Hyperplasia, Reticulum Cell 1 (2%) Necrosis 1 (2%) Thymus (49) (49) Hemorrhage 4 (8%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (42) (38) Cyst 1 (2%) 1 (3%) Hyperplasia 5 (12%) 2 (5%) Skin (50) (50) Cyst Epithelial Inclusion 1 (2%) 1 (2%) Hyperkeratosis 1 (2%) Subcutaneous Tissue, Fibrosis 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) Femur, Osteopetrosis 2 (4%) Skeletal Muscle (1) (5) Hemorrhage 3 (60%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) Compression 2 (4%) Hydrocephalus 1 (2%) Spinal Cord (5) Hemorrhage 1 (20%) Necrosis 1 (20%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) Edema 5 (10%) Hemorrhage 1 (2%) 21 (42%) Infiltration Cellular, Polymorphonuclear 1 (2%) Infiltration Cellular, Histiocyte 42 (84%) 32 (64%) a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 05161-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC RIDDELLIINE Date: 12/15/00 Route: GAVAGE Time: 12:05:56 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 1.0 MG/KG/DY MG/KG/DY ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Metaplasia, Osseous 2 (4%) 1 (2%) Alveolar Epithelium, Hyperplasia 3 (6%) 1 (2%) Nose (50) (50) Foreign Body 5 (10%) 5 (10%) Hemorrhage 1 (2%) 2 (4%) Inflammation, Chronic 7 (14%) 5 (10%) Respiratory Epithelium, Hyperplasia 7 (14%) 6 (12%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM None ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) Glomerulosclerosis 1 (2%) Hydronephrosis 2 (4%) Infarct 1 (2%) Inflammation, Suppurative 1 (2%) Nephropathy 47 (94%) 38 (76%) Renal Tubule, Hyaline Droplet 1 (2%) 3 (6%) Renal Tubule, Necrosis 6 (12%) Renal Tubule, Pigmentation 1 (2%) 4 (8%) Transitional Epithelium, Hyperplasia 2 (4%) Urinary Bladder (50) (50) Hemorrhage 1 (2%) Transitional Epithelium, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 12 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------