TDMS Study 99035-01 Pathology Tables
NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 FINAL #1 Facility: Battelle Columbus Laboratory Chemical CAS #: 556-52-5 Lock Date: 09/24/01 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: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) FEMALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 15 15 15 15 15 Early Deaths Moribund Sacrifice 2 1 2 1 4 Natural Death 1 2 Survivors Terminal Sacrifice 13 14 12 14 9 Animals Examined Microscopically 15 15 15 15 15 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Liver (15) (15) (15) (15) (15) Angiectasis, Focal 1 [1.0] 2 [1.0] Eosinophilic Focus 1 Hematopoietic Cell Proliferation 2 [1.0] 3 [1.7] 1 [2.0] 1 [1.0] 2 [1.0] Infiltration Cellular, Lymphoid 3 [1.7] 1 [1.0] 1 [1.0] 1 [1.0] Inflammation 1 [1.0] Inflammation, Chronic 11 [1.0] 10 [1.0] 8 [1.0] 8 [1.0] 7 [1.0] Mixed Cell Focus 1 1 Necrosis, Focal 5 [1.6] 2 [1.0] 2 [2.0] Midzonal, Fatty Change 1 [2.0] Stomach, Forestomach (15) (15) (15) (15) (15) Epithelium, Hyperplasia 1 [1.0] 4 [1.3] Stomach, Glandular (15) (15) (15) (15) (15) Metaplasia, Squamous 1 [2.0] Mineralization 4 [1.3] 2 [1.0] Epithelium, Ectasia 1 [1.0] Muscularis, Mineralization 2 [1.5] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (15) (15) (15) (15) (15) Inflammation, Chronic 1 [2.0] Myocardium, Mineralization 1 [1.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (15) (15) (15) (15) (15) Hematopoietic Cell Proliferation 1 [2.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 2 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) FEMALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hyperplasia, Focal 2 [1.0] 1 [2.0] Mineralization 1 [1.0] Vacuolization Cytoplasmic, Focal 1 [1.0] Subcapsular, Hyperplasia 15 [1.5] 15 [1.5] 10 [1.5] 14 [1.6] 15 [1.7] Pituitary Gland (15) (15) (15) (15) (15) Necrosis 1 [3.0] Pars Distalis, Hyperplasia, Focal 1 [2.0] 1 [1.0] 2 [1.5] 1 [1.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (1) Pigmentation, Melanin 1 [2.0] Ovary (15) (15) (15) (15) (15) Cyst 4 [1.0] 2 [2.0] Uterus (15) (15) (15) (15) (15) Endometrium, Hyperplasia, Cystic 13 [1.6] 14 [1.8] 10 [1.9] 14 [1.8] 9 [1.9] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (15) (15) (15) (15) (15) Hyperplasia 1 [3.0] Lymph Node (13) (15) (15) (13) (14) Lumbar, Hyperplasia, Lymphoid 1 [1.0] Mediastinal, Hyperplasia, Lymphoid 2 [2.5] 1 [3.0] Pancreatic, Hyperplasia, Lymphoid 1 [4.0] Renal, Hyperplasia, Lymphoid 1 [4.0] Lymph Node, Mandibular (15) (15) (15) (15) (15) Hyperplasia, Lymphoid 1 [3.0] 1 [3.0] Lymph Node, Mesenteric (15) (15) (15) (15) (15) Hyperplasia, Lymphoid 1 [2.0] Inflammation, Suppurative 1 [2.0] Spleen (15) (15) (15) (15) (15) Hematopoietic Cell Proliferation 9 [1.8] 5 [2.8] 10 [2.5] 10 [1.6] 10 [2.1] Thymus (15) (15) (15) (15) (15) Atrophy 2 [2.5] 1 [2.0] 3 [3.3] 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 3 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) FEMALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (15) (15) (15) (15) (15) Hyperplasia 1 [2.0] Skin (15) (15) (15) (15) (15) Subcutaneous Tissue, Edema 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (15) (15) (15) (15) (15) Hyperostosis 1 [3.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (15) (15) (15) (15) (15) Cerebellum, Gliosis 1 [2.0] Cerebellum, Neuronopathy 1 [1.0] 3 [2.7] Cerebrum, Cyst Epithelial Inclusion 1 Cerebrum, Hemorrhage 1 [1.0] Medulla, Gliosis 2 [1.5] Medulla, Neuronopathy 3 [2.3] Thalamus, Gliosis 1 [1.0] Thalamus, Neuronopathy 3 [3.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (15) (15) (15) (15) (15) Inflammation 8 [2.0] 8 [1.8] 7 [1.9] 5 [2.2] 3 [1.7] Inflammation, Granulomatous 1 [1.0] Alveolar Epithelium, Hyperplasia, Focal 1 [4.0] 2 [3.0] 1 [3.0] 1 [1.0] Arteriole, Inflammation, Acute 1 [1.0] Bronchus, Foreign Body 1 [2.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM None ____________________________________________________________________________________________________________________________________ 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: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) FEMALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (15) (15) (15) (15) (15) Infiltration Cellular, Lymphoid 1 [3.0] Metaplasia, Osseous 1 [1.0] Nephropathy 12 [1.0] 12 [1.0] 10 [1.0] 14 [1.0] 9 [1.0] Renal Tubule, Accumulation, Hyaline Droplet 2 [2.5] 1 [2.0] 3 [2.0] Urinary Bladder (15) (15) (15) (15) (15) Inflammation, Chronic 1 [2.0] a Number of animals examined microscopically at site and number of animals with lesion b Average severity grade (1-minimal;2-mild;3-moderate;4-marked) Page 5 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) MALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 15 15 15 15 15 Early Deaths Natural Death 2 1 1 1 3 Moribund Sacrifice 1 4 Dosing Accident 1 Survivors Terminal Sacrifice 13 14 13 14 7 Animals Examined Microscopically 15 15 15 15 15 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (1) Inflammation, Acute 1 [3.0] Intestine Small, Jejunum (15) (15) (15) (15) (15) Peyer's Patch, Hyperplasia, Atypical 1 [3.0] Peyer's Patch, Hyperplasia, Lymphoid 1 [2.0] Liver (15) (15) (15) (15) (15) Angiectasis, Focal 1 [2.0] Basophilic Focus 1 Degeneration, Cystic 1 [1.0] Eosinophilic Focus 1 Fatty Change, Focal 1 [1.0] Hematopoietic Cell Proliferation 1 [1.0] 2 [1.0] 1 [1.0] Hemorrhage 1 [1.0] Infiltration Cellular, Lymphoid 1 [1.0] 2 [1.0] 2 [1.0] 1 [1.0] Inflammation, Chronic 6 [1.0] 9 [1.0] 8 [1.0] 9 [1.0] 2 [1.0] Mixed Cell Focus 1 Necrosis, Focal 1 [3.0] 2 [2.0] 2 [2.5] 5 [2.2] Mesentery (1) Fat, Necrosis 1 [3.0] Stomach, Forestomach (15) (15) (15) (15) (15) Inflammation, Chronic 1 [3.0] Ulcer 1 [2.0] 3 [1.7] Epithelium, Hyperplasia 1 [2.0] 1 [2.0] 6 [2.5] Stomach, Glandular (15) (15) (15) (15) (15) Inflammation, Chronic 1 [2.0] Mineralization 10 [1.5] 5 [1.6] 1 [1.0] Ulcer 1 [2.0] Epithelium, Hyperplasia 1 [1.0] Glands, Ectasia 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 6 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) MALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Muscularis, Mineralization 1 [2.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (15) (15) (15) (15) (15) Infiltration Cellular, Mast Cell 1 [1.0] Epicardium, Inflammation, Chronic 1 [1.0] Myocardium, Degeneration 2 [1.5] 2 [1.0] Myocardium, Mineralization 2 [1.0] 1 [1.0] 5 [1.6] Myocardium, Necrosis 2 [2.5] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (15) (15) (15) (14) (15) Hyperplasia, Focal 1 [1.0] 1 [2.0] Subcapsular, Hyperplasia 1 [1.0] 2 [1.0] 2 [1.0] 3 [1.0] 1 [1.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (15) (15) (15) (15) (15) Fibrosis 1 [3.0] Preputial Gland (1) Inflammation, Suppurative 1 [4.0] Testes (15) (15) (15) (15) (15) Germinal Epithelium, Degeneration 1 [2.0] 1 [3.0] Germinal Epithelium, Mineralization 1 [1.0] Germinal Epithelium, Necrosis 1 [1.0] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Lymph Node (14) (14) (15) (13) (13) Mediastinal, Hyperplasia, Lymphoid 1 [3.0] Lymph Node, Mandibular (15) (15) (15) (15) (15) Hyperplasia, Lymphoid 2 [2.0] 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 7 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) MALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Inflammation, Suppurative 1 [3.0] Necrosis 1 [3.0] Lymph Node, Mesenteric (15) (15) (15) (14) (15) Hematopoietic Cell Proliferation 1 [2.0] Hyperplasia, Lymphoid 2 [2.0] 1 [3.0] 1 [4.0] Inflammation, Suppurative 1 [2.0] 1 [3.0] Necrosis 1 [2.0] Spleen (15) (15) (15) (15) (15) Angiectasis 1 [2.0] Atrophy 1 [2.0] 2 [1.5] Hematopoietic Cell Proliferation 4 [2.0] 7 [1.7] 7 [1.4] 5 [2.0] 5 [2.2] Thymus (15) (15) (15) (15) (15) Atrophy 2 [2.0] 1 [3.0] 4 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (15) (15) (15) (15) (15) Ulcer 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (15) (15) (15) (15) (15) Hyperostosis 1 [1.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (15) (15) (15) (15) (15) Mineralization 1 [1.0] Cerebellum, Gliosis 2 [1.5] Cerebellum, Hemorrhage, Focal 1 [2.0] Cerebellum, Neuronopathy 3 [3.3] Cerebrum, Hemorrhage 1 [3.0] Cerebrum, Necrosis, Focal 2 [3.0] Hippocampus, Hemorrhage 1 [3.0] Hippocampus, Necrosis 1 [3.0] 1 [3.0] Medulla, Gliosis 2 [1.0] Medulla, Neuronopathy 3 [1.0] Thalamus, Gliosis 2 [1.0] Thalamus, Neuronopathy 5 [2.2] Spinal Cord (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 8 NTP Experiment-Test: 99035-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: 26-39 WEEKS WITH AVERAGE SEVERITY GRADES[b] Date: 03/31/04 Route: GAVAGE TRANSGENIC MODEL EVALUATION II (GLYCIDOL) Time: 13:23:06 ____________________________________________________________________________________________________________________________________ P16(INK4A)/(+/-) (C57BL/6) MALE 0 MG/KG 25 MG/KG 50 MG/KG 100 200 MG/KG MG/KG ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM - CONT Axon, Degeneration 1 [2.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (15) (15) (15) (15) (15) Hemorrhage 1 [3.0] Inflammation 3 [2.0] 7 [2.3] 5 [2.4] 4 [2.0] 2 [1.5] Inflammation, Granulomatous 1 [1.0] Alveolar Epithelium, Hyperplasia, Focal 2 [1.0] 2 [1.0] 2 [1.5] Bronchiole, Hyperplasia 1 [2.0] Vein, Thrombosis 1 [3.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM None ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (15) (15) (15) (15) (15) Hydronephrosis 1 [4.0] Infarct 1 [2.0] Nephropathy 4 [1.0] 5 [1.0] 5 [1.0] 4 [1.0] 4 [1.0] Renal Tubule, Accumulation, Hyaline Droplet 1 [3.0] 1 [2.0] Urinary Bladder (15) (15) (15) (15) (15) Inflammation, Chronic 1 [4.0] Transitional Epithelium, Hyperplasia 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 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------