TDMS Study 93020-08 Pathology Tables
NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 FINAL #1 MICE Facility: Southern Research Institute Chemical CAS #: 693-13-0 Lock Date: 03/14/03 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 b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 1 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 5 5 6 4 Moribund Sacrifice 12 11 4 5 Accidently Killed 1 1 1 Survivors Terminal Sacrifice 33 32 38 40 Natural Death 1 Moribund Sacrifice 1 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Gallbladder (42) (47) (42) (47) Cyst 1 [1.0] Intestine Large, Cecum (46) (45) (44) (47) Cyst 1 [1.0] Edema 1 [3.0] Intestine Small, Duodenum (46) (46) (44) (47) Hyperplasia, Lymphoid 1 [3.0] Perforation 1 [3.0] Intestine Small, Jejunum (47) (45) (44) (46) Inflammation, Focal 1 [2.0] Epithelium, Hyperplasia, Focal 1 [2.0] Peyer's Patch, Hyperplasia, Lymphoid 1 [3.0] Intestine Small, Ileum (46) (44) (45) (47) Peyer's Patch, Hyperplasia, Lymphoid 1 [3.0] Liver (50) (50) (50) (50) Angiectasis, Focal 1 [2.0] 2 [2.5] Clear Cell Focus 1 Congestion 1 [2.0] Eosinophilic Focus 6 1 6 Hematopoietic Cell Proliferation 2 [3.0] 1 [2.0] Hyperplasia, Focal, Lymphoid 1 [2.0] 2 [2.0] Infiltration Cellular, Polymorphonuclear 1 [3.0] 1 [3.0] Infiltration Cellular, Mixed Cell 16 [1.6] 9 [1.7] 10 [1.2] 22 [1.2] Mineralization, Focal 1 [3.0] Necrosis, Focal 1 [2.0] Hepatocyte, Basophilic Focus 1 1 1 Hepatocyte, Clear Cell Focus 3 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 2 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Hepatocyte, Eosinophilic Focus 4 Hepatocyte, Karyomegaly 1 [1.0] Hepatocyte, Mixed Cell Focus 2 1 6 Hepatocyte, Necrosis, Focal 3 [1.3] 3 [3.0] 1 [1.0] 1 [1.0] Hepatocyte, Vacuolization Cytoplasmic 5 [1.8] 3 [2.3] 1 [1.0] 5 [2.2] Mesentery (23) (20) (14) (18) Hemorrhage 1 [3.0] Infiltration Cellular, Lymphoid 1 [3.0] Infiltration Cellular, Mixed Cell 1 [3.0] Inflammation 3 [3.3] 5 [3.2] 1 [2.0] Artery, Inflammation 1 [2.0] Fat, Necrosis, Focal 17 [2.6] 13 [2.7] 9 [2.3] 15 [2.3] Pancreas (50) (48) (50) (50) Inflammation, Focal 1 [2.0] Acinus, Atrophy, Diffuse 2 [4.0] Acinus, Atrophy, Focal 1 [4.0] 2 [3.5] 1 [1.0] 3 [2.7] Duct, Cyst, Focal, Multiple 2 [3.5] 1 [4.0] Stomach, Forestomach (50) (49) (50) (50) Diverticulum 1 [1.0] 1 [1.0] Erosion 2 [2.0] 2 [1.5] Inflammation, Focal 1 [2.0] 1 [2.0] 1 [3.0] Ulcer 1 [2.0] 1 [2.0] 2 [2.5] Epithelium, Hyperplasia 4 [1.8] 4 [1.8] 2 [2.0] 1 [3.0] Stomach, Glandular (49) (48) (47) (50) Erosion 1 [1.0] Glands, Hyperplasia, Focal 1 [2.0] Tooth (1) (1) (1) (2) Malformation 1 [3.0] 1 [3.0] Peridontal Tissue, Inflammation, Chronic 1 [3.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (49) (50) Cardiomyopathy 3 [1.7] 1 [1.0] 1 [1.0] Infiltration Cellular, Polymorphonuclear 1 [2.0] Infiltration Cellular, Mixed Cell 1 [2.0] Inflammation, Chronic, Focal 1 [2.0] Thrombosis 4 [3.0] 2 [3.5] Artery, Inflammation, Chronic 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 3 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (49) (50) Accessory Adrenal Cortical Nodule 2 [1.0] 1 [1.0] 1 [1.0] 3 [1.3] Angiectasis 1 [2.0] Cytoplasmic Alteration, Focal 1 [1.0] 2 [1.5] 1 [2.0] Degeneration, Cystic 1 [2.0] 1 [3.0] 1 [2.0] Infiltration Cellular, Polymorphonuclear 1 [3.0] Inflammation, Suppurative 1 [3.0] Necrosis, Focal 1 [3.0] Adrenal Medulla (49) (50) (49) (49) Angiectasis 1 [2.0] Hyperplasia 1 [2.0] Inflammation, Suppurative 1 [2.0] Islets, Pancreatic (50) (49) (50) (50) Hyperplasia 2 [2.0] 1 [2.0] Parathyroid Gland (46) (43) (49) (49) Cyst 2 [2.0] 2 [2.0] 1 [2.0] Pituitary Gland (48) (50) (50) (46) Angiectasis 3 [2.0] 1 [2.0] 1 [2.0] 3 [1.7] Cyst 1 [3.0] Hemorrhage 1 [3.0] Pars Distalis, Cytoplasmic Alteration, Focal 2 [1.5] 4 [1.5] 1 [1.0] Pars Distalis, Degeneration, Cystic, Focal 1 [2.0] Pars Distalis, Hyperplasia, Focal 3 [2.3] 2 [2.0] 7 [2.0] 3 [2.0] Pars Intermedia, Hyperplasia, Focal 1 [2.0] Thyroid Gland (50) (50) (50) (50) Cyst 2 [2.0] 3 [2.7] 1 [2.0] Inflammation, Chronic, Focal 1 [1.0] C-Cell, Hyperplasia 2 [1.5] Follicle, Degeneration, Cystic, Focal 14 [1.8] 14 [1.9] 18 [1.7] 12 [1.9] Follicular Cell, Hyperplasia, Focal 1 [1.0] 11 [1.5] 9 [1.3] 4 [1.5] Follicular Cell, Vacuolization Cytoplasmic, Focal 1 [2.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (5) (8) (3) (4) Mediastinum, Infiltration Cellular, Lymphoid 1 [3.0] 1 [2.0] Mediastinum, Inflammation, Suppurative 1 [3.0] 1 [3.0] Nasal, 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 4 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (46) (48) (48) (47) Degeneration, Cystic 1 [3.0] Inflammation, Chronic 1 [3.0] Ovary (49) (50) (49) (49) Angiectasis 2 [3.5] 3 [2.7] 1 [4.0] 1 [3.0] Cyst 14 [2.6] 16 [2.6] 13 [2.8] 18 [2.6] Hemorrhage 2 [2.5] Hyperplasia, Lymphoid 1 [3.0] Inflammation, Suppurative 2 [3.5] 2 [3.0] 2 [3.5] Thrombosis 2 [3.0] 1 [4.0] 1 [4.0] Bilateral, Cyst 1 [3.0] Bilateral, Inflammation, Suppurative 1 [3.0] 1 [3.0] Interstitial Cell, Hyperplasia 1 [3.0] Oviduct (3) (1) Inflammation, Suppurative 3 [3.0] Uterus (50) (50) (50) (50) Hemorrhage 1 [3.0] Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] Inflammation, Suppurative 5 [2.6] 8 [3.0] 6 [2.7] 2 [1.5] Thrombosis 1 [3.0] Cervix, Hypertrophy 1 [3.0] Endometrium, Hyperplasia, Cystic 46 [2.7] 44 [2.9] 47 [2.8] 49 [2.8] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (49) (50) (50) (49) Hyperplasia 14 [3.1] 5 [3.4] 10 [2.9] 2 [3.0] Lymph Node (11) (13) (10) (10) Hyperplasia, Lymphoid 1 [3.0] Bronchial, Hyperplasia, Lymphoid 1 [3.0] Iliac, Ectasia 1 [3.0] 1 [3.0] 3 [2.7] Iliac, Hemorrhage 2 [3.0] Iliac, Hyperplasia, Lymphoid 2 [2.5] 2 [3.5] 2 [3.0] 2 [2.5] Inguinal, Hyperplasia, Lymphoid 1 [3.0] Mediastinal, Ectasia 1 [3.0] Mediastinal, Hemorrhage 1 [3.0] Mediastinal, Hyperplasia 1 [3.0] Mediastinal, Hyperplasia, Lymphoid 1 [2.0] 2 [3.0] 1 [3.0] 3 [3.0] Pancreatic, Hemorrhage 1 [3.0] Pancreatic, Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] 1 [3.0] Renal, Ectasia 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Renal, Hyperplasia, Lymphoid 1 [3.0] 1 [4.0] 2 [2.5] Lymph Node, Mandibular (47) (49) (49) (48) Hemorrhage 1 [3.0] Hyperplasia, Lymphoid 6 [3.0] 4 [3.0] 2 [2.5] 1 [3.0] Lymph Node, Mesenteric (47) (48) (49) (50) Ectasia 1 [3.0] 1 [3.0] 5 [3.2] 2 [3.0] Hematopoietic Cell Proliferation 1 [3.0] Hemorrhage 1 [3.0] Hyperplasia, Lymphoid 3 [3.0] 6 [3.2] 2 [3.0] 5 [3.0] Spleen (49) (49) (50) (50) Accessory Spleen 1 Atrophy 1 [2.0] Congestion 1 [3.0] Hematopoietic Cell Proliferation 24 [2.8] 21 [2.8] 18 [2.6] 13 [2.8] Hyperplasia, Histiocytic 1 [3.0] Hyperplasia, Lymphoid 6 [2.7] 12 [2.6] 12 [2.5] 6 [2.3] Capsule, Inflammation, Chronic, Focal 1 [2.0] Thymus (46) (48) (44) (47) Hyperplasia, Lymphoid 5 [2.8] 4 [3.0] 4 [3.0] 1 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (49) (49) Dilatation 1 [2.0] Hyperplasia 1 [2.0] Skin (50) (50) (50) (50) Ulcer 1 [3.0] Control Dermis, Hyperplasia, Focal 1 [1.0] Control Dermis, Inflammation, Focal 1 [2.0] 1 [2.0] 1 [1.0] Control Epidermis, Hyperplasia, Focal 1 [3.0] 1 [1.0] Epidermis, Hyperplasia, Focal 1 [3.0] Site of Application - Dermis, Fibrosis 1 [1.0] Site of Application - Dermis, Inflammation, Focal 3 [1.3] 2 [2.5] 7 [1.4] 2 [1.5] Site of Application - Epidermis, Hyperplasia 5 [2.0] 3 [1.7] 7 [1.4] 7 [1.3] Site of Application, Ulcer 2 [3.0] 1 [2.0] Subcutaneous Tissue, Angiectasis, Focal 1 [2.0] Subcutaneous Tissue, Edema 1 [3.0] 2 [2.5] 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM - CONT Bone (50) (50) (50) (50) Hyperostosis 3 [2.3] 1 [2.0] 1 [2.0] 2 [2.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Compression, Focal 2 [3.0] 2 [3.5] 1 [3.0] Hemorrhage, Focal 1 [1.0] 2 [2.0] Infarct 1 Inflammation, Focal 1 [1.0] Cerebellum, Hippocampus, Necrosis 1 [2.0] Cerebrum, Atrophy, Focal 1 [4.0] Hippocampus, Necrosis, Acute 1 [3.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 2 [3.0] 1 [3.0] 1 [2.0] Foreign Body 1 [1.0] Hemorrhage 1 [3.0] Hyperplasia, Histiocytic 1 [3.0] 1 [3.0] Infiltration Cellular, Polymorphonuclear 2 [3.0] Mineralization, Focal 1 [2.0] Alveolar Epithelium, Hyperplasia, Focal 1 [1.0] 2 [1.0] 1 [2.0] 2 [1.5] Mediastinum, Hyperplasia, Lymphoid 2 [3.0] Nose (50) (50) (49) (50) Inflammation 1 [2.0] Nasolacrimal Duct, Inflammation 1 [2.0] 1 [2.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (47) (48) (49) (49) Atrophy 1 [4.0] 2 [4.0] Phthisis Bulbi 1 Cornea, Hyperplasia, Squamous 1 [2.0] 1 [1.0] Cornea, Inflammation, Chronic 1 [2.0] Iris, Synechia 1 Lens, Cataract 1 [3.0] Harderian Gland (50) (49) (50) (50) Cyst 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM - CONT Inflammation 2 [2.5] Epithelium, Hyperplasia, Focal 1 [2.0] 1 [2.0] 1 [1.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (49) (49) (50) (49) Congestion 1 [3.0] Cyst 1 [1.0] 4 [1.8] Hydronephrosis 1 [3.0] 1 [3.0] Hyperplasia, Lymphoid 2 [2.5] 2 [2.5] 1 [2.0] 1 [2.0] Infarct 3 [1.3] 2 [2.0] 1 [2.0] 1 [2.0] Infiltration Cellular, Polymorphonuclear 1 [2.0] Infiltration Cellular, Mixed Cell 1 [2.0] Inflammation 1 [3.0] 1 [3.0] Metaplasia, Focal, Osseous 5 [1.6] 2 [2.0] 1 [1.0] Nephropathy 13 [1.1] 8 [1.0] 11 [1.1] 18 [1.2] Capsule, Congestion 1 [2.0] Papilla, Necrosis 1 [3.0] Renal Tubule, Accumulation, Hyaline Droplet 3 [3.0] 1 [2.0] 2 [3.0] Renal Tubule, Necrosis 1 [4.0] Renal Tubule, Vacuolization Cytoplasmic, Focal 1 [2.0] 1 [1.0] 1 [2.0] Urinary Bladder (50) (50) (49) (50) Angiectasis 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Moribund Sacrifice 5 1 2 5 Natural Death 6 9 10 8 Accidently Killed 1 Survivors Terminal Sacrifice 38 40 38 36 Moribund Sacrifice 1 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Gallbladder (45) (42) (43) (41) Cyst 1 [2.0] 1 [2.0] 2 [1.5] Epithelium, Degeneration, Hyaline 1 [3.0] 1 [3.0] Epithelium, Hyperplasia 1 [3.0] Intestine Small, Duodenum (46) (44) (44) (40) Ectopic Tissue 1 [2.0] Serosa, Inflammation, Chronic 1 [3.0] Intestine Small, Jejunum (46) (43) (44) (40) Cyst 1 [3.0] Inflammation, Focal 1 [3.0] 1 [2.0] Necrosis 1 [4.0] Peyer's Patch, Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] 1 [3.0] Intestine Small, Ileum (46) (44) (44) (40) Peyer's Patch, Hyperplasia, Lymphoid 1 [3.0] Liver (50) (50) (50) (49) Atrophy 1 [2.0] Basophilic Focus 1 Clear Cell Focus 2 1 1 2 Eosinophilic Focus 2 1 1 4 Fibrosis, Focal 1 [2.0] Hemorrhage, Focal 1 [3.0] Hepatodiaphragmatic Nodule 1 [2.0] Hyperplasia, Focal, Histiocytic 1 [3.0] Infarct 1 [3.0] 1 [4.0] Infiltration Cellular, Polymorphonuclear 1 [4.0] Infiltration Cellular, Mixed Cell 8 [1.4] 5 [1.4] 5 [1.4] 6 [1.3] Inflammation, Focal, Granulomatous 1 [3.0] Pigmentation, Focal 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 9 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Thrombosis 1 [4.0] Bile Duct, Hyperplasia 1 [2.0] 1 [3.0] Capsule, Inflammation, Chronic 1 [3.0] Hepatocyte, Clear Cell Focus 19 17 12 8 Hepatocyte, Eosinophilic Focus 2 Hepatocyte, Mixed Cell Focus 1 2 2 Hepatocyte, Necrosis, Focal 5 [1.8] 3 [2.3] 2 [2.5] 7 [1.9] Hepatocyte, Vacuolization Cytoplasmic 18 [1.9] 17 [2.0] 17 [1.9] 18 [2.2] Mesentery (49) (49) (50) (50) Fibrosis, Focal 1 [2.0] Inflammation 1 [3.0] 1 [3.0] Inflammation, Chronic 1 [3.0] Artery, Inflammation 1 [3.0] Fat, Necrosis, Focal 4 [2.3] 2 [3.0] 4 [2.0] 4 [2.0] Pancreas (49) (50) (49) (49) Inflammation, Focal 1 [2.0] Necrosis, Focal 1 [3.0] 1 [2.0] Acinus, Atrophy, Focal 3 [2.7] Serosa, Inflammation, Chronic 1 [3.0] Salivary Glands (50) (50) (50) (50) Atrophy 1 [3.0] Stomach, Forestomach (50) (50) (50) (50) Diverticulum 1 [2.0] Erosion 1 [2.0] Inflammation, Focal 1 [2.0] 1 [2.0] Ulcer 1 [2.0] Epithelium, Cyst 1 [1.0] Epithelium, Hyperplasia 2 [2.0] 2 [2.0] 3 [1.7] 2 [2.0] Stomach, Glandular (50) (47) (48) (47) Erosion 4 [1.5] 1 [1.0] 1 [1.0] Tooth (18) (11) (15) (12) Malformation 18 [2.5] 11 [2.5] 15 [2.5] 12 [2.5] Peridontal Tissue, Inflammation, Chronic 1 [2.0] Pulp, Inflammation 1 [2.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) Cardiomyopathy 1 [2.0] 1 [2.0] Infiltration Cellular, Mixed Cell 1 [1.0] Inflammation, Chronic, Focal 1 [1.0] Thrombosis 1 [4.0] 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 10 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM - CONT Artery, Inflammation, Chronic 1 [2.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (49) Accessory Adrenal Cortical Nodule 3 [1.0] 2 [1.5] 2 [1.5] 2 [2.0] Cytoplasmic Alteration, Focal 9 [1.3] 5 [1.2] 7 [1.4] 4 [1.5] Degeneration, Cystic 1 [1.0] Hyperplasia, Focal, Histiocytic 1 [2.0] Hypertrophy 1 [4.0] Vacuolization Cytoplasmic, Focal 1 [2.0] Adrenal Medulla (49) (50) (50) (49) Angiectasis 1 [3.0] Hyperplasia, Focal 1 [2.0] Islets, Pancreatic (49) (50) (49) (50) Hyperplasia 2 [2.5] 2 [2.5] 2 [2.5] 1 [2.0] Parathyroid Gland (49) (50) (46) (47) Cyst 1 [1.0] 2 [2.5] 1 [3.0] Pituitary Gland (48) (47) (50) (49) Cyst 1 [1.0] 2 [1.0] 3 [1.7] 3 [2.0] Pars Distalis, Cytoplasmic Alteration, Focal 1 [2.0] 5 [1.4] Pars Distalis, Hyperplasia, Focal 1 [2.0] Thyroid Gland (49) (50) (50) (50) C-Cell, Hyperplasia 1 [2.0] 3 [1.7] Follicle, Degeneration, Cystic, Focal 4 [2.0] 6 [2.2] 8 [1.8] 6 [1.7] Follicular Cell, Hyperplasia, Focal 7 [1.9] 7 [1.3] 8 [1.5] 3 [1.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (3) (2) Hemorrhage 1 [3.0] Abdominal, Cyst 1 [3.0] ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (50) (50) (50) (50) Granuloma Sperm 1 [3.0] 1 [2.0] Inflammation, Chronic 1 [2.0] 1 [2.0] Spermatocele 1 [3.0] Preputial Gland (50) (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 11 NTP Experiment-Test: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Cyst 2 [3.0] Degeneration, Cystic 3 [2.7] 1 [3.0] 1 [3.0] 4 [3.0] Hyperplasia, Lymphoid 1 [4.0] Inflammation, Chronic 11 [3.1] 8 [3.3] 10 [2.9] 6 [3.0] Prostate (50) (50) (50) (50) Inflammation 1 [4.0] 2 [3.0] Epithelium, Hyperplasia, Focal 2 [2.0] 1 [2.0] Seminal Vesicle (50) (50) (50) (50) Cyst 1 [3.0] Testes (50) (50) (50) (50) Atrophy 1 [2.0] 1 [2.0] Interstitial Cell, Hyperplasia, Focal 1 [1.0] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (49) (50) (50) (50) Hyperplasia 9 [2.9] 13 [2.9] 12 [2.9] 7 [2.9] Thrombosis 1 [1.0] Lymph Node (6) (5) (5) (4) Bronchial, Hyperplasia, Lymphoid 1 [3.0] Iliac, Hyperplasia, Lymphoid 1 [3.0] Inguinal, Hyperplasia, Lymphoid 2 [3.0] 3 [3.0] 4 [2.8] 1 [3.0] Mediastinal, Hyperplasia, Lymphoid 1 [2.0] Pancreatic, Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] 1 [3.0] Lymph Node, Mandibular (47) (48) (47) (47) Hyperplasia, Histiocytic 1 [2.0] Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] Lymph Node, Mesenteric (50) (48) (49) (48) Ectasia 1 [3.0] Hematopoietic Cell Proliferation 1 [3.0] Hemorrhage 3 [3.0] 1 [3.0] 3 [3.0] Hyperplasia, Lymphoid 3 [2.7] 2 [3.0] 4 [3.0] 2 [3.5] Spleen (49) (50) (50) (47) Atrophy 1 [3.0] 1 [2.0] Fibrosis, Focal 1 [3.0] Hematopoietic Cell Proliferation 15 [2.8] 13 [2.6] 14 [2.8] 13 [2.6] Hyperplasia, Lymphoid 2 [3.0] 5 [2.4] 1 [2.0] 1 [3.0] Thrombosis 1 [3.0] Capsule, Inflammation, Chronic 1 [2.0] Thymus (47) (44) (47) (46) Cyst 2 [2.0] 1 [2.0] 2 [2.5] 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (50) (50) (50) Ulcer 1 [3.0] Epidermis, Hyperplasia, Focal 1 [1.0] 1 [1.0] Site of Application - Dermis, Inflammation, Focal 2 [2.0] 2 [2.0] 9 [1.4] 1 [1.0] Site of Application - Epidermis, Hyperplasia 2 [2.0] 3 [2.3] 10 [1.8] 1 [1.0] Site of Application, Ulcer 1 [2.0] 1 [3.0] Subcutaneous Tissue, Angiectasis, Focal 1 [3.0] Subcutaneous Tissue, Edema 2 [2.5] Subcutaneous Tissue, Inflammation, Chronic, Focal 1 [3.0] Subcutaneous Tissue, Thrombosis 1 [3.0] Subcutaneous Tissue, Site of Application, Infiltration Cellular 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Hyperostosis 2 [2.0] 2 [2.0] 1 [1.0] Skeletal Muscle (2) (2) (2) (5) Inflammation, Chronic 1 [2.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM None ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 1 [2.0] 1 [3.0] Hyperplasia, Histiocytic 1 [2.0] 1 [1.0] 4 [3.0] Hyperplasia, Lymphoid 1 [2.0] 1 [1.0] Inflammation, Chronic, Focal 1 [2.0] Alveolar Epithelium, Hyperplasia, Focal 4 [1.3] 2 [1.5] 1 [1.0] 3 [1.7] Mediastinum, Hyperplasia, Lymphoid 1 [2.0] Nose (49) (50) (50) (50) Inflammation 2 [2.5] 1 [2.0] Nasolacrimal Duct, Cyst 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: 93020-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/19/04 Route: SKIN APPLICATION DIISOPROPYLCARBODIIMIDE Time: 09:22:22 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 10 MG/KG 20 MG/KG 40 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Nasolacrimal Duct, Hyperplasia, Focal 1 [2.0] 2 [2.0] 1 [3.0] Nasolacrimal Duct, Inflammation 1 [2.0] 2 [3.0] 3 [1.7] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (46) (46) (47) (44) Atrophy 1 [4.0] Inflammation 1 [2.0] Cornea, Hyperplasia, Squamous 1 [2.0] 1 [1.0] Cornea, Inflammation, Chronic 2 [2.0] 3 [2.3] 1 [2.0] 3 [2.7] Cornea, Necrosis, Focal 1 [3.0] 1 [3.0] Retrobulbar, Inflammation 1 [2.0] Harderian Gland (50) (50) (50) (50) Degeneration, Cystic, Focal 1 [2.0] Inflammation 1 [4.0] 1 [1.0] Epithelium, Hyperplasia, Focal 3 [2.0] 3 [1.7] 1 [2.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (48) (50) (48) Cyst 3 [1.7] 10 [2.0] 5 [2.0] 3 [1.7] Hydronephrosis 2 [2.5] 1 [3.0] Infarct 2 [1.5] 3 [2.0] 1 [2.0] 1 [2.0] Infiltration Cellular, Mixed Cell 1 [2.0] Inflammation 3 [2.3] Metaplasia, Focal, Osseous 4 [1.8] 2 [2.0] 1 [1.0] Nephropathy 46 [1.4] 44 [1.6] 41 [1.6] 40 [1.4] Pelvis, Dilatation 1 [3.0] Renal Tubule, Hyperplasia, Focal 2 [1.0] 3 [1.7] 1 [1.0] Urinary Bladder (50) (50) (49) (50) Inflammation 1 [3.0] 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 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------