TDMS Study 96007-05 Pathology Tables
NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 FINAL #3/RATS Facility: Battelle Columbus Laboratory Chemical CAS #: 57117-31-4 Lock Date: 07/25/02 Cage Range: All Reasons For Removal: 25018 Dosing Accident 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: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 98 98 98 98 98 98 Early Deaths Natural Death 7 10 10 8 14 11 Moribund Sacrifice 21 20 17 19 19 19 Dosing Accident 1 2 1 Survivors Terminal Sacrifice 25 22 24 25 20 23 Animals Examined Microscopically 53 53 53 53 53 53 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (53) (53) (52) (53) (53) (53) Cyst 2 [3.0] Perforation 1 [0.0] 2 [3.0] 1 [4.0] Muscularis, Inflammation 2 [1.5] 1 [1.0] 1 [1.0] 1 [2.0] 1 [2.0] Periesophageal Tissue, Inflammation 1 [3.0] 2 [3.0] 2 [3.0] 1 [3.0] Intestine Large, Colon (53) (53) (53) (53) (51) (53) Edema 1 [2.0] Inflammation 1 [2.0] 1 [2.0] Parasite Metazoan 2 Intestine Large, Rectum (53) (53) (53) (53) (52) (53) Parasite Metazoan 4 5 5 1 1 1 Artery, Inflammation, Chronic Active 1 [3.0] 1 [3.0] Intestine Large, Cecum (53) (53) (53) (52) (51) (53) Inflammation 1 [2.0] Artery, Inflammation, Chronic Active 1 [3.0] 2 [2.5] Artery, Mineralization 1 [2.0] Intestine Small, Ileum (53) (53) (53) (52) (52) (53) Parasite Metazoan 1 Liver (53) (53) (53) (52) (53) (53) Angiectasis 6 [1.5] 3 [1.3] 4 [1.8] 1 [2.0] 1 [2.0] Basophilic Focus 10 11 9 10 12 6 Basophilic Focus, Multiple 12 12 11 6 3 1 Cholangiofibrosis 1 [1.0] 3 [1.3] 3 [1.3] 5 [2.2] Clear Cell Focus 11 1 7 2 3 Clear Cell Focus, Multiple 2 5 3 1 6 8 Degeneration, Cystic 1 [1.0] Eosinophilic Focus 7 11 9 9 11 10 Eosinophilic Focus, Multiple 8 2 9 9 12 18 Fatty Change, Diffuse 1 [1.0] 4 [1.3] 10 [1.4] 12 [1.1] 20 [1.1] 26 [1.3] 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 2 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Fatty Change, Focal 5 [1.2] 6 [2.0] 5 [1.0] 6 [1.3] 6 [1.3] 4 [1.0] Hematopoietic Cell Proliferation 24 [1.1] 28 [1.3] 27 [1.1] 24 [1.0] 39 [1.1] 31 [1.1] Hemorrhage 1 [2.0] Hepatodiaphragmatic Nodule 3 3 3 1 1 1 Hyperplasia, Nodular 3 8 12 Inflammation 47 [1.1] 44 [1.2] 47 [1.1] 50 [1.2] 48 [1.2] 50 [1.3] Mixed Cell Focus 5 1 2 2 1 Mixed Cell Focus, Multiple 28 24 23 27 25 25 Necrosis 4 [2.5] 10 [2.1] 3 [2.0] 3 [2.3] 6 [2.0] 18 [1.8] Pigmentation 13 [1.1] 11 [1.1] 21 [1.3] 44 [1.5] 42 [1.8] 48 [1.9] Toxic Hepatopathy 2 [1.0] 3 [1.0] 8 [1.1] 27 [1.1] 44 [1.7] Artery, Inflammation, Chronic Active 1 [1.0] Bile Duct, Cyst 7 [2.3] 4 [2.3] 2 [3.0] 3 [2.0] 2 [2.0] 7 [1.7] Bile Duct, Fibrosis 1 [1.0] 4 [1.8] 2 [1.0] 2 [1.5] 3 [1.0] 6 [1.3] Bile Duct, Hyperplasia 3 [1.3] 2 [1.0] 2 [1.0] 2 [1.0] 1 [1.0] 13 [1.6] Centrilobular, Degeneration 4 [2.0] 2 [1.5] 3 [2.3] 4 [1.5] 4 [2.3] 5 [2.4] Hepatocyte, Hypertrophy 2 [1.0] 13 [1.0] 17 [1.0] 17 [1.0] 24 [1.0] 34 [1.2] Hepatocyte, Multinucleated 4 [1.0] 13 [1.0] 18 [1.3] 35 [1.2] Oval Cell, Hyperplasia 1 [1.0] 4 [1.3] 2 [1.0] 6 [1.2] 15 [1.1] 35 [1.4] Portal, Fibrosis 1 [1.0] Mesentery (1) (2) (1) (3) (2) (4) Inflammation 1 [2.0] Necrosis 1 [3.0] Artery, Inflammation, Chronic Active 1 [3.0] 2 [3.5] 1 [4.0] 4 [3.3] Fat, Necrosis 1 [3.0] 1 [2.0] 1 [3.0] Oral Mucosa (52) (53) (52) (53) (53) (53) Gingival, Cyst 1 [3.0] Gingival, Hyperplasia 1 [1.0] Gingival, Hyperplasia, Squamous 15 [1.1] 11 [1.4] 16 [1.4] 19 [1.2] 22 [1.1] 20 [1.4] Pancreas (53) (53) (53) (52) (52) (52) Cyst 1 [2.0] Cytoplasmic Alteration 3 [2.0] Inflammation, Chronic Active 2 [1.0] 1 [2.0] 1 [1.0] 1 [1.0] 4 [2.0] Lipomatosis 1 [2.0] Acinus, Atrophy 3 [1.7] 1 [4.0] 1 [1.0] 1 [2.0] 3 [2.7] Acinus, Hyperplasia 1 [3.0] Acinus, Vacuolization Cytoplasmic 2 [1.0] 23 [1.1] Artery, Inflammation, Chronic Active 1 [1.0] 2 [2.0] 1 [1.0] 2 [2.5] 4 [2.3] 11 [3.3] Duct, Dilatation 1 [4.0] Salivary Glands (53) (53) (51) (53) (51) (51) Atrophy 1 [2.0] 2 [1.5] Duct, Inflammation 1 [3.0] Stomach, Forestomach (53) (53) (53) (53) (52) (53) 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: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Cyst 1 [3.0] Edema 1 [2.0] Hyperkeratosis 1 [2.0] Hyperplasia, Squamous 4 [1.8] 1 [1.0] 5 [1.4] 6 [2.5] 3 [2.7] 10 [2.1] Inflammation 1 [2.0] 1 [1.0] 2 [2.5] 2 [2.5] 2 [2.0] Mineralization 1 [2.0] Ulcer 1 [1.0] 2 [1.5] 2 [2.0] 1 [3.0] 1 [2.0] Artery, Inflammation, Chronic Active 1 [2.0] 3 [2.7] Stomach, Glandular (53) (53) (53) (53) (52) (53) Erosion 1 [2.0] 2 [2.0] 1 [2.0] Hyperplasia 1 [2.0] Inflammation 1 [2.0] 1 [2.0] Mineralization 2 [1.0] 9 [1.1] 1 [1.0] 3 [1.3] 2 [2.0] 4 [1.5] Ulcer 1 [2.0] Artery, Inflammation, Chronic Active 1 [3.0] 1 [2.0] Serosa, Inflammation 1 [2.0] Tooth (33) (25) (22) (30) (29) (29) Peridontal Tissue, Inflammation 33 [1.6] 25 [1.4] 22 [1.1] 30 [1.6] 29 [1.1] 29 [1.3] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (53) (53) (53) (53) (53) (53) Aorta, Mineralization 1 [3.0] 1 [3.0] 2 [2.5] Aorta, Adventitia, Inflammation, Chronic Active 1 [4.0] Heart (53) (53) (52) (53) (53) (52) Cardiomyopathy 15 [1.1] 12 [1.0] 19 [1.1] 13 [1.0] 18 [1.0] 24 [1.1] Hemorrhage 2 [2.0] Infiltration Cellular, Mononuclear Cell 1 [1.0] Inflammation 1 [2.0] 1 [3.0] 1 [2.0] Mineralization 1 [2.0] 1 [2.0] 1 [2.0] Artery, Inflammation, Chronic Active 1 [2.0] 2 [1.5] Epicardium, Inflammation 1 [3.0] 1 [2.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (53) (53) (53) (52) (53) (53) Angiectasis 31 [1.5] 37 [1.4] 30 [1.4] 33 [1.4] 27 [1.2] 35 [1.3] Atrophy 3 [3.3] 1 [4.0] 4 [2.3] Degeneration, Cystic 4 [2.0] 17 [1.9] 14 [2.3] 18 [2.2] 12 [2.1] 14 [2.4] Hematopoietic Cell Proliferation 1 [2.0] 1 [1.0] 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 4 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hemorrhage 1 [4.0] 1 [3.0] Hyperplasia 8 [2.4] 10 [2.0] 10 [2.1] 7 [2.3] 10 [2.1] 11 [1.8] Hypertrophy 42 [1.7] 43 [1.9] 43 [2.1] 46 [2.1] 44 [2.1] 45 [2.1] Necrosis 4 [2.3] 2 [2.0] 2 [2.0] Vacuolization Cytoplasmic 9 [1.4] 13 [1.2] 14 [1.6] 7 [1.9] 17 [1.2] 9 [1.4] Adrenal Medulla (53) (53) (53) (52) (53) (53) Hyperplasia 11 [2.3] 12 [2.2] 14 [1.9] 14 [1.9] 7 [1.9] 10 [1.9] Islets, Pancreatic (53) (53) (53) (52) (52) (52) Hyperplasia 2 [2.5] Parathyroid Gland (49) (51) (44) (51) (49) (49) Hyperplasia 1 [2.0] 1 [2.0] 1 [2.0] 1 [2.0] Hypertrophy 1 [2.0] Pituitary Gland (53) (53) (53) (53) (53) (53) Angiectasis 20 [1.9] 21 [2.5] 20 [2.5] 13 [2.4] 12 [2.4] 14 [2.2] Atrophy 1 [4.0] Cyst 2 [1.5] 1 [2.0] 1 [3.0] 1 [2.0] Cytoplasmic Alteration 1 [1.0] 1 [1.0] Vacuolization Cytoplasmic 2 [1.0] 2 [1.0] 1 [1.0] Pars Distalis, Hyperplasia 22 [2.4] 16 [2.4] 14 [2.3] 11 [2.5] 15 [2.3] 19 [2.6] Pars Intermedia, Hyperplasia 1 [2.0] Rathke's Cleft, Pars Intermedia, Hyperplasia 1 [2.0] Thyroid Gland (53) (53) (51) (53) (51) (51) Inflammation 1 [3.0] C-Cell, Hyperplasia 15 [2.1] 16 [2.2] 9 [2.3] 13 [1.9] 9 [2.0] 11 [1.8] Follicle, Cyst 1 [2.0] 1 [2.0] 1 [2.0] Follicular Cell, Hypertrophy 7 [1.6] 13 [1.2] 24 [1.3] 24 [1.2] 24 [1.5] 22 [1.5] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (53) (51) (53) (53) (50) (53) Hyperplasia, Squamous 1 [2.0] Inflammation 52 [1.7] 47 [1.8] 46 [1.7] 51 [1.7] 47 [1.5] 47 [1.5] Duct, Cyst 40 [2.3] 37 [2.3] 34 [2.6] 41 [2.4] 44 [2.0] 40 [2.2] Ovary (53) (53) (53) (52) (52) (53) Atrophy 43 [4.0] 40 [4.0] 38 [4.0] 43 [4.0] 45 [4.0] 45 [3.9] Cyst 11 [2.2] 18 [2.1] 20 [2.1] 17 [2.3] 18 [2.3] 13 [2.5] Fibrosis 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 5 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Inflammation, Chronic Active 1 [4.0] 1 [3.0] 1 [4.0] Oviduct (1) (1) Cyst 1 [3.0] Inflammation, Chronic Active 1 [3.0] Uterus (53) (53) (53) (52) (52) (53) Adenomyosis 1 [2.0] 1 [2.0] 1 [3.0] Cyst 1 [3.0] 1 [2.0] Hemorrhage 1 [2.0] 2 [2.5] Inflammation, Chronic Active 5 [2.6] 3 [2.3] 3 [3.3] 4 [3.0] 3 [2.3] Inflammation, Suppurative 3 [1.7] 6 [1.3] 1 [1.0] 7 [1.4] 3 [1.7] 4 [1.0] Metaplasia, Squamous 17 [1.8] 25 [1.8] 21 [1.8] 36 [1.8] 31 [1.9] 35 [1.9] Ulcer 1 [3.0] 3 [2.7] 1 [2.0] Cervix, Cyst 1 [3.0] Endometrium, Hyperplasia, Cystic 31 [2.4] 29 [2.1] 29 [2.1] 33 [2.2] 39 [2.2] 37 [2.1] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (53) (53) (53) (53) (53) (53) Atrophy 2 [2.0] Hyperplasia 38 [2.8] 32 [2.9] 37 [3.1] 35 [2.9] 42 [2.9] 41 [2.8] Hyperplasia, Reticulum Cell 1 [3.0] Lymph Node (5) (4) (4) (4) (3) (7) Hyperplasia, Plasma Cell 1 [2.0] Iliac, Ectasia 1 [3.0] Lumbar, Ectasia 2 [2.0] 1 [3.0] 1 [2.0] Lumbar, Hemorrhage 2 [2.5] 1 [2.0] Lumbar, Hyperplasia, Histiocytic 1 [2.0] 1 [2.0] Lumbar, Hyperplasia, Plasma Cell 1 [3.0] 1 [3.0] 1 [3.0] 1 [2.0] Mediastinal, Ectasia 2 [1.5] 2 [2.0] Mediastinal, Hemorrhage 1 [2.0] 1 [1.0] Mediastinal, Hyperplasia, Lymphoid 1 [2.0] Mediastinal, Hyperplasia, Plasma Cell 1 [3.0] 1 [3.0] 1 [3.0] 2 [1.5] Popliteal, Ectasia 1 [2.0] Lymph Node, Mandibular (53) (53) (51) (53) (51) (51) Congestion 1 [2.0] Ectasia 1 [2.0] 2 [2.0] 1 [2.0] 1 [2.0] 1 [2.0] Hyperplasia, Histiocytic 1 [2.0] Hyperplasia, Lymphoid 1 [3.0] 1 [4.0] Hyperplasia, Plasma Cell 38 [2.1] 40 [2.2] 38 [2.1] 31 [2.1] 30 [2.2] 29 [2.2] Lymph Node, Mesenteric (53) (53) (53) (52) (52) (53) Atrophy 1 [3.0] Hemorrhage 1 [2.0] 1 [2.0] 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 6 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Hyperplasia, Histiocytic 1 [2.0] Hyperplasia, Lymphoid 1 [3.0] 1 [2.0] 1 [3.0] Hyperplasia, Plasma Cell 1 [2.0] 1 [2.0] Spleen (53) (53) (53) (52) (52) (51) Accessory Spleen 1 1 Congestion 1 [2.0] 1 [3.0] Hematopoietic Cell Proliferation 49 [2.0] 49 [2.2] 48 [2.3] 51 [1.9] 46 [2.2] 50 [2.0] Hemorrhage 1 [2.0] Infarct 1 [2.0] Necrosis 1 [3.0] Pigmentation 52 [1.7] 45 [1.6] 50 [1.9] 48 [1.8] 49 [1.9] 51 [1.9] Lymphatic, Angiectasis 1 [2.0] Lymphoid Follicle, Atrophy 7 [2.0] 8 [2.1] 7 [2.3] 6 [2.7] 12 [2.4] 4 [2.3] Red Pulp, Atrophy 2 [2.0] Red Pulp, Hyperplasia 1 [3.0] Thymus (53) (49) (50) (52) (49) (51) Atrophy 43 [2.3] 36 [2.6] 36 [2.7] 44 [2.8] 39 [3.1] 48 [3.6] Hemorrhage 1 [2.0] 1 [2.0] 1 [2.0] 1 [2.0] Hyperplasia, Lymphoid 1 [2.0] Inflammation 1 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (53) (53) (53) (53) (53) (53) Cyst 1 [3.0] 2 [2.5] 5 [2.2] 4 [2.5] 3 [2.3] Hyperplasia 33 [1.3] 29 [1.3] 26 [1.5] 20 [1.6] 20 [1.2] 17 [1.1] Inflammation, Granulomatous 2 [1.5] 4 [2.3] 3 [2.0] 4 [2.0] 4 [2.0] 3 [2.0] Skin (53) (53) (53) (53) (53) (53) Inflammation 2 [3.0] 1 [3.0] Ulcer 2 [3.0] 1 [3.0] Conjunctiva, Inflammation 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (53) (53) (53) (53) (53) (53) Edema 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: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM - CONT Gliosis 1 [2.0] Hemorrhage 1 [3.0] 1 [3.0] Hydrocephalus 1 [2.0] 1 [2.0] 1 [2.0] Peripheral Nerve (1) (1) Radicular Neuropathy 1 [2.0] Spinal Cord (1) (1) Degeneration 1 [3.0] Hemorrhage 1 [3.0] Necrosis 1 [2.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (53) (53) (53) (53) (53) (52) Edema 1 [2.0] Hemorrhage 1 [4.0] Infiltration Cellular, Histiocyte 44 [1.7] 44 [1.7] 40 [1.7] 40 [1.7] 41 [1.6] 36 [1.6] Inflammation 5 [1.4] 8 [1.4] 7 [1.3] 6 [1.5] 7 [1.9] 8 [1.6] Metaplasia, Squamous 2 [1.0] 4 [1.5] 3 [1.7] Mineralization 1 [2.0] 1 [2.0] Alveolar Epithelium, Hyperplasia 14 [1.1] 17 [1.1] 12 [1.2] 20 [1.2] 8 [1.1] 3 [1.0] Alveolar Epithelium, Metaplasia, Bronchiolar 5 [1.0] 6 [1.0] 5 [1.2] 9 [1.3] 23 [1.6] 28 [1.5] Alveolus, Metaplasia, Squamous 1 [1.0] Nose (53) (53) (53) (53) (53) (53) Inflammation 8 [1.1] 3 [1.3] 8 [1.1] 11 [1.2] 7 [1.1] 6 [1.3] Mineralization 1 [1.0] Olfactory Epithelium, Metaplasia 1 [2.0] Respiratory Epithelium, Hyperplasia 1 [2.0] 1 [1.0] 2 [1.5] 1 [2.0] 6 [2.0] 3 [2.0] Respiratory Epithelium, Metaplasia 1 [2.0] Septum, Inflammation 1 [1.0] 2 [1.0] 3 [1.0] 2 [1.0] 5 [1.4] 3 [1.7] Squamous Epithelium, Hyperplasia 1 [1.0] 1 [2.0] 1 [1.0] Trachea (53) (53) (52) (53) (53) (53) Inflammation 1 [3.0] 1 [2.0] Artery, Peritracheal Tissue, Inflammation, Chronic Active 1 [3.0] Peritracheal Tissue, Inflammation 1 [3.0] 2 [3.0] 1 [3.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (53) (53) (52) (53) (52) (52) Hemorrhage 1 [3.0] Inflammation 1 [3.0] 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 8 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 NG/KG ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM - CONT Cornea, Inflammation 1 [2.0] Lens, Degeneration 1 [3.0] Retina, Atrophy 1 [2.0] Retina, Degeneration 1 [3.0] Harderian Gland (53) (53) (53) (53) (52) (52) Inflammation 16 [1.0] 9 [1.0] 10 [1.0] 13 [1.1] 8 [1.1] 6 [1.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (53) (53) (53) (52) (53) (53) Accumulation, Hyaline Droplet 1 [1.0] Calculus Micro Observation Only 5 2 4 1 2 3 Cyst 1 [2.0] 2 [2.0] 1 [2.0] Fibrosis 1 [3.0] Hemorrhage 1 [2.0] Inflammation, Chronic Active 1 [3.0] 1 [1.0] Inflammation, Suppurative 2 [1.0] 1 [1.0] 1 [1.0] 3 [1.0] 2 [1.0] 2 [1.5] Mineralization 37 [1.0] 45 [1.0] 42 [1.0] 43 [1.1] 43 [1.0] 31 [1.1] Necrosis 2 [2.5] Nephropathy 34 [1.1] 39 [1.2] 35 [1.2] 42 [1.4] 36 [1.4] 45 [1.5] Pigmentation 2 [2.0] Artery, Inflammation, Chronic Active 1 [3.0] 1 [2.0] Capsule, Hemorrhage 1 [3.0] Pelvis, Dilatation 1 [3.0] 2 [2.0] 1 [3.0] Pelvis, Inflammation 1 [2.0] 1 [2.0] 5 [2.0] 1 [2.0] Renal Tubule, Dilatation 1 [2.0] Renal Tubule, Hyperplasia 1 [1.0] Renal Tubule, Necrosis 1 [2.0] Renal Tubule, Nephropathy 1 [1.0] Transitional Epithelium, Hyperplasia 2 [1.0] 2 [1.5] 1 [1.0] 2 [1.0] 6 [2.7] 5 [2.0] Urinary Bladder (53) (52) (53) (53) (51) (53) Infiltration Cellular, Lymphoid 1 [3.0] Inflammation 2 [2.5] 3 [1.7] 1 [2.0] 1 [1.0] 6 [1.5] 1 [2.0] Transitional Epithelium, Hyperplasia 1 [2.0] 4 [2.5] 4 [1.5] Transitional Epithelium, Metaplasia, Squamous 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 9 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 200 NG/ KG STOP ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 Early Deaths Moribund Sacrifice 25 Natural Death 10 Survivors Terminal Sacrifice 15 Animals Examined Microscopically 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Rectum (50) Parasite Metazoan 2 Liver (50) Angiectasis 1 [2.0] Basophilic Focus 9 Basophilic Focus, Multiple 4 Cholangiofibrosis 3 [2.7] Clear Cell Focus 4 Clear Cell Focus, Multiple 2 Degeneration, Cystic 1 [2.0] Eosinophilic Focus 8 Eosinophilic Focus, Multiple 14 Fatty Change, Diffuse 6 [1.2] Fatty Change, Focal 7 [1.1] Hematopoietic Cell Proliferation 31 [1.1] Hepatodiaphragmatic Nodule 1 Inflammation 48 [1.1] Mixed Cell Focus 5 Mixed Cell Focus, Multiple 19 Necrosis 11 [2.1] Pigmentation 48 [1.6] Toxic Hepatopathy 9 [1.0] Bile Duct, Cyst 2 [2.0] Bile Duct, Fibrosis 1 [1.0] Bile Duct, Hyperplasia 1 [2.0] Centrilobular, Degeneration 7 [2.4] Hepatocyte, Hypertrophy 14 [1.0] Hepatocyte, Multinucleated 25 [1.2] Oval Cell, Hyperplasia 3 [1.0] Mesentery (2) 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: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 200 NG/ KG STOP ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Inflammation, Chronic Active 1 [3.0] Necrosis 1 [3.0] Oral Mucosa (50) Gingival, Hyperplasia, Squamous 14 [1.2] Pancreas (49) Acinus, Vacuolization Cytoplasmic 2 [1.0] Artery, Inflammation, Chronic Active 1 [2.0] Stomach, Forestomach (50) Erosion 1 [2.0] Hyperkeratosis 1 [2.0] Hyperplasia, Squamous 5 [2.2] Inflammation 1 [3.0] Ulcer 1 [2.0] Stomach, Glandular (50) Mineralization 3 [1.3] Tooth (24) Peridontal Tissue, Inflammation 24 [1.2] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) Cardiomyopathy 13 [1.1] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (48) Angiectasis 29 [1.4] Degeneration, Cystic 12 [1.8] Hyperplasia 7 [2.3] Hypertrophy 36 [2.1] Necrosis 3 [2.3] Vacuolization Cytoplasmic 10 [1.3] Bilateral, Inflammation, Chronic Active 1 [3.0] Adrenal Medulla (48) Hyperplasia 7 [1.9] Parathyroid Gland (47) Fibrosis 1 [3.0] Pituitary Gland (49) Angiectasis 13 [2.3] Cyst 1 [3.0] Cytoplasmic Alteration 2 [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 11 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 200 NG/ KG STOP ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Vacuolization Cytoplasmic 2 [1.5] Pars Distalis, Hyperplasia 19 [2.6] Thyroid Gland (48) C-Cell, Hyperplasia 15 [1.7] Follicular Cell, Hypertrophy 23 [1.3] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) Inflammation 48 [1.8] Duct, Cyst 39 [2.3] Ovary (47) Atrophy 39 [4.0] Cyst 12 [2.3] Uterus (49) Congestion 1 [2.0] Hemorrhage 1 [2.0] Inflammation, Chronic Active 7 [1.9] Inflammation, Suppurative 3 [1.3] Metaplasia, Squamous 28 [2.1] Endometrium, Hyperplasia, Cystic 35 [2.5] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) Hyperplasia 43 [3.0] Lymph Node (3) Iliac, Ectasia 1 [3.0] Iliac, Hyperplasia, Plasma Cell 1 [3.0] Lumbar, Ectasia 1 [2.0] Lumbar, Hyperplasia, Plasma Cell 1 [3.0] Renal, Ectasia 1 [2.0] Renal, Hyperplasia, Plasma Cell 1 [2.0] Lymph Node, Mandibular (49) Ectasia 1 [2.0] Hyperplasia, Lymphoid 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 12 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 200 NG/ KG STOP ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Hyperplasia, Plasma Cell 29 [2.0] Spleen (49) Hematopoietic Cell Proliferation 49 [2.2] Pigmentation 48 [1.7] Lymphoid Follicle, Atrophy 2 [2.0] Thymus (49) Atrophy 44 [2.9] Hemorrhage 1 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) Cyst 3 [2.3] Hyperplasia 19 [1.4] Inflammation 1 [3.0] Inflammation, Granulomatous 1 [2.0] Skin (50) Hyperkeratosis 1 [1.0] Lip, Inflammation, Chronic Active 1 [4.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) Osteopetrosis 1 [2.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (49) Mineralization 1 [1.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) Congestion 1 [3.0] Hemorrhage 2 [2.0] Infiltration Cellular, Histiocyte 30 [1.4] Inflammation 5 [1.6] Metaplasia, Squamous 1 [3.0] Mineralization 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 13 NTP Experiment-Test: 96007-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 09/30/03 Route: GAVAGE TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) Time: 12:03:03 ____________________________________________________________________________________________________________________________________ SPRAGUE-DAWLEY RATS FEMALE 200 NG/ KG STOP ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Alveolar Epithelium, Hyperplasia 6 [1.0] Alveolar Epithelium, Metaplasia, Bronchiolar 7 [1.1] Nose (50) Inflammation 7 [1.0] Nasolacrimal Duct, Inflammation 1 [3.0] Respiratory Epithelium, Hyperplasia 2 [2.0] Trachea (50) Inflammation 1 [2.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (49) Retina, Atrophy 1 [2.0] Harderian Gland (49) Inflammation 6 [1.3] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) Accumulation, Hyaline Droplet 3 [2.0] Calculus Micro Observation Only 1 Infarct 1 [3.0] Inflammation 1 [4.0] Inflammation, Suppurative 2 [1.0] Mineralization 41 [1.0] Nephropathy 35 [1.1] Pelvis, Dilatation 1 [3.0] Pelvis, Inflammation 1 [2.0] Transitional Epithelium, Hyperplasia 3 [1.7] Urinary Bladder (50) Inflammation 2 [3.0] Transitional Epithelium, Hyperplasia 3 [1.7] 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 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------