TDMS Study 91005-07 Pathology Tables
NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 FINAL #1 RATS Facility: Southern Research Institute Chemical CAS #: 7220-79-3 Lock Date: 09/05/03 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: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 6 4 9 11 Moribund Sacrifice 9 13 5 3 Dosing Accident 1 Survivors Terminal Sacrifice 35 32 34 35 Natural Death 2 Other 1 Animals Examined Microscopically 50 49 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (49) (50) (50) Perforation 1 [3.0] Intestine Large, Colon (50) (48) (49) (48) Cyst 1 [4.0] Intestine Small, Duodenum (49) (48) (49) (48) Ectopic Tissue 1 [2.0] Liver (50) (49) (50) (50) Basophilic Focus 37 34 38 40 Clear Cell Focus 8 5 9 8 Degeneration, Cystic 1 [1.0] 1 [2.0] 1 [1.0] Eosinophilic Focus 3 2 Hepatodiaphragmatic Nodule 7 [0.0] 4 [2.0] 7 [0.0] 4 [2.0] Inflammation, Chronic 6 [2.0] 4 [1.8] 4 [1.8] 5 [1.8] Necrosis, Focal 1 [2.0] 1 [1.0] Bile Duct, Hyperplasia 7 [2.4] 5 [1.8] 6 [1.7] 2 [2.0] Centrilobular, Necrosis 2 [1.5] 1 [2.0] Hepatocyte, Vacuolization Cytoplasmic 4 [2.3] 4 [1.8] Mesentery (17) (14) (12) (8) Accessory Spleen 1 [2.0] Fat, Necrosis 17 [2.8] 14 [2.6] 11 [2.6] 8 [2.4] Oral Mucosa (2) (1) Pharyngeal, Cyst 1 [3.0] 1 [2.0] Pancreas (49) (48) (48) (49) Atrophy 26 [1.5] 20 [1.4] 23 [1.3] 23 [1.5] Inflammation 1 [1.0] Acinus, Hyperplasia, Focal 3 [1.7] 1 [2.0] 2 [2.0] 1 [2.0] Salivary Glands (50) (49) (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 2 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Inflammation 1 [1.0] Stomach, Forestomach (50) (49) (49) (49) Edema 2 [2.5] 3 [2.3] 1 [3.0] Erosion 1 [1.0] Inflammation, Chronic Active 1 [1.0] 2 [1.0] Ulcer 4 [2.3] 3 [3.0] 1 [3.0] 1 [2.0] Epithelium, Hyperplasia 2 [2.0] 2 [2.0] 2 [1.5] 3 [1.3] Stomach, Glandular (50) (49) (48) (49) Edema 2 [2.0] 1 [2.0] 1 [2.0] Erosion 2 [2.5] 2 [2.5] Ulcer 2 [2.0] 1 [3.0] 1 [2.0] Tongue (1) (1) (1) (1) Cyst 1 [2.0] Hyperplasia 1 [2.0] 1 [2.0] Inflammation 1 [3.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (49) (50) (50) Cardiomyopathy 36 [1.3] 41 [1.2] 36 [1.2] 32 [1.2] Thrombosis 1 [2.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (49) (50) (50) Accessory Adrenal Cortical Nodule 9 [1.3] 7 [1.3] 8 [1.3] 12 [1.3] Degeneration, Fatty 11 [1.4] 13 [1.8] 13 [1.9] 8 [1.4] Hyperplasia, Focal 5 [1.4] 8 [1.6] 8 [1.4] 6 [2.0] Hypertrophy, Focal 12 [1.9] 11 [2.1] 13 [2.2] 7 [2.0] Necrosis 2 [3.0] 1 [2.0] Adrenal Medulla (50) (49) (50) (50) Hyperplasia 1 [2.0] 2 [1.0] 1 [3.0] Islets, Pancreatic (49) (48) (48) (49) Hyperplasia 13 [1.0] 15 [1.0] 15 [1.1] 15 [1.0] Metaplasia, Hepatocyte 2 [1.5] Pituitary Gland (50) (49) (50) (50) Pars Distalis, Angiectasis 28 [2.0] 27 [1.9] 29 [2.0] 21 [2.0] Pars Distalis, Cyst 21 [2.1] 19 [1.6] 16 [1.7] 23 [2.0] Pars Distalis, Hyperplasia, Focal 5 [2.0] 8 [1.8] 6 [2.0] 6 [1.8] Pars Intermedia, Cyst 1 [2.0] Thyroid Gland (50) (49) (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 3 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Ultimobranchial Cyst 2 [1.5] 1 [1.0] C-Cell, Hyperplasia 10 [2.1] 11 [1.4] 7 [1.9] 5 [2.0] Follicle, Cyst 2 [2.0] 1 [1.0] 2 [1.0] 4 [2.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (48) (50) (50) Cyst 4 [2.3] 7 [2.0] 4 [1.8] 6 [2.0] Inflammation, Chronic 1 [2.0] 5 [1.6] 2 [3.0] 4 [2.3] Ovary (50) (49) (50) (50) Cyst 11 [1.9] 4 [1.8] 9 [2.0] 10 [1.8] Uterus (50) (49) (50) (50) Cyst 1 3 2 3 Hemorrhage 1 [2.0] 1 [3.0] Hydrometra 1 [3.0] 4 [1.0] 2 [1.5] 1 [2.0] Cervix, Cyst 1 Endometrium, Hyperplasia, Cystic 4 [2.5] 1 [1.0] 2 [2.0] Vagina (1) Cyst 1 ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (49) (50) (50) Hyperplasia 8 [2.4] 8 [2.8] 9 [2.6] 6 [2.5] Lymph Node (15) (8) (11) (3) Mediastinal, Congestion 1 [3.0] Mediastinal, Hyperplasia, Lymphoid 5 [2.0] 7 [2.1] 8 [2.0] 2 [2.0] Pancreatic, Hyperplasia, Lymphoid 1 [2.0] 1 [2.0] 1 [2.0] Lymph Node, Mesenteric (49) (49) (50) (50) Hyperplasia, Lymphoid 1 [2.0] 1 [1.0] Spleen (49) (48) (49) (49) Fibrosis 2 [2.0] Hematopoietic Cell Proliferation 3 [4.0] 5 [2.4] 7 [2.7] 8 [1.6] Necrosis 1 [3.0] Capsule, Fibrosis 8 [1.0] 17 [1.1] 12 [1.1] 20 [1.0] Lymphoid Follicle, Atrophy 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: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Lymphoid Follicle, Hyperplasia 1 [3.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (49) (50) (50) Cyst 2 [3.0] 1 [1.0] Galactocele 1 1 1 Hyperplasia 18 [2.3] 19 [2.1] 9 [2.0] 7 [2.6] Hyperplasia, Atypical 3 [1.3] 3 [2.0] 1 [2.0] Duct, Dilatation 31 [2.6] 28 [2.5] 29 [2.4] 24 [2.4] Duct, Hyperplasia 2 [2.0] 1 [2.0] Skin (50) (49) (50) (50) Inflammation, Chronic 2 [1.5] Inflammation, Chronic Active 1 [4.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (49) (50) (50) Inflammation 1 [4.0] Cranium, Osteopetrosis 1 [2.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (49) (50) (50) Compression 3 [2.3] 8 [2.1] 6 [2.2] 5 [2.0] Hemorrhage 1 [2.0] 1 [2.0] 1 [4.0] ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) (50) (50) Congestion 5 [1.2] 2 [1.0] 5 [1.0] 8 [1.5] Foreign Body 1 [3.0] Infiltration Cellular, Histiocyte 41 [1.0] 37 [1.0] 39 [1.0] 38 [1.0] Inflammation, Chronic 29 [1.0] 33 [1.0] 29 [1.0] 33 [1.0] Inflammation, Suppurative 1 [3.0] Necrosis 1 [3.0] Alveolar Epithelium, Hyperplasia 1 [3.0] 4 [2.0] 3 [2.3] 2 [2.5] Nose (50) (49) (50) (50) Foreign Body 4 [1.8] 3 [1.0] 1 [1.0] 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 5 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Inflammation, Chronic 8 [1.9] 7 [1.0] 9 [1.8] 6 [1.7] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (49) (50) (50) Cataract 1 [2.0] 2 [3.0] 5 [2.4] 3 [2.0] Inflammation, Chronic 2 [4.0] Anterior Chamber, Inflammation 1 [2.0] Cornea, Inflammation, Chronic 1 [2.0] 1 [2.0] 2 [2.5] Retina, Degeneration 2 [2.5] 2 [4.0] 4 [3.5] 2 [4.0] Harderian Gland (50) (49) (50) (50) Inflammation, Chronic 3 [1.7] 3 [1.3] 3 [1.3] 4 [1.0] Pigmentation 2 [2.0] 2 [2.0] 1 [2.0] 1 [2.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (49) (50) (50) Cyst 1 [2.0] 1 [2.0] Infarct 1 [2.0] 2 [1.5] 2 [2.0] Nephropathy 14 [1.0] 15 [1.1] 21 [1.2] 16 [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: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 6 10 5 7 Moribund Sacrifice 13 7 5 10 Dosing Accident 1 2 Survivors Natural Death 1 Terminal Sacrifice 29 33 39 30 Moribund Sacrifice 1 1 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Perforation 2 [3.5] Intestine Large, Colon (50) (50) (50) (50) Inflammation 1 [2.0] Intestine Large, Cecum (49) (50) (49) (47) Inflammation, Chronic 1 [2.0] Intestine Small, Duodenum (50) (50) (50) (48) Ectopic Tissue 1 [2.0] 1 [2.0] Ulcer 1 [2.0] Intestine Small, Ileum (48) (50) (49) (48) Hyperplasia, Lymphoid 1 [3.0] Liver (50) (50) (50) (50) Basophilic Focus 5 6 8 6 Clear Cell Focus 14 13 16 12 Degeneration, Cystic 5 [1.8] 3 [1.3] 2 [1.5] 1 [2.0] Eosinophilic Focus 5 1 4 3 Hepatodiaphragmatic Nodule 9 [2.1] 2 [2.0] 3 [2.5] 4 [2.0] Inflammation, Chronic 1 [1.0] 1 [1.0] Necrosis, Focal 1 [2.0] 1 [1.0] Bile Duct, Hyperplasia 41 [2.5] 35 [2.3] 38 [1.9] 37 [2.0] Centrilobular, Necrosis 2 [1.5] 1 [2.0] 2 [2.0] Hepatocyte, Vacuolization Cytoplasmic 5 [2.2] 1 [2.0] 2 [2.5] 3 [2.3] Serosa, Inflammation 1 [2.0] Mesentery (16) (11) (9) (12) Accessory Spleen 1 [2.0] Fibrosis 1 [2.0] Fat, Necrosis 14 [2.6] 9 [2.3] 8 [3.0] 7 [2.6] 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: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Oral Mucosa (1) (4) Pharyngeal, Cyst 2 [4.0] Pharyngeal, Inflammation 2 [2.5] Pancreas (50) (50) (50) (50) Atrophy 43 [2.1] 31 [1.8] 35 [2.0] 32 [1.9] Atrophy, Focal 1 [1.0] Cyst 1 [2.0] Inflammation, Chronic 1 [2.0] Acinus, Hyperplasia, Focal 4 [2.0] 6 [1.7] 15 [1.9] 12 [1.8] Salivary Glands (50) (50) (50) (50) Hyperplasia 1 [2.0] Stomach, Forestomach (50) (50) (50) (50) Edema 6 [2.5] 1 [2.0] 2 [2.5] Erosion 3 [2.3] 1 [1.0] Ulcer 4 [3.5] 1 [2.0] 2 [2.5] 2 [2.5] Epithelium, Hyperplasia 4 [2.3] 3 [1.7] 3 [1.3] Stomach, Glandular (50) (50) (50) (50) Edema 1 [2.0] 2 [2.0] Erosion 4 [2.0] 2 [3.0] 1 [3.0] 1 [2.0] Hyperplasia 1 [2.0] Inflammation 1 [2.0] Mineralization 1 [2.0] Ulcer 2 [3.5] 1 [2.0] 2 [2.0] 1 [4.0] ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) Cardiomyopathy 47 [1.6] 46 [1.5] 47 [1.4] 45 [1.7] Mineralization 1 [3.0] Thrombosis 1 [2.0] 1 [1.0] Pericardium, Inflammation, Granulomatous 1 [3.0] ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 23 [1.1] 23 [1.2] 28 [1.3] 25 [1.2] Degeneration, Fatty 7 [1.9] 6 [1.3] 7 [1.7] 2 [1.5] Hyperplasia, Focal 6 [1.2] 5 [1.6] 5 [1.6] 5 [1.2] Hypertrophy, Focal 6 [2.3] 5 [1.6] 9 [1.9] 8 [2.0] Necrosis 1 [2.0] 1 [3.0] Adrenal Medulla (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 8 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hyperplasia 7 [2.0] 12 [1.8] 8 [1.6] 2 [2.0] Thrombosis 1 [3.0] Islets, Pancreatic (50) (50) (50) (50) Hyperplasia 13 [1.2] 13 [1.7] 17 [1.8] 26 [1.4] Metaplasia, Hepatocyte 1 [2.0] Pituitary Gland (50) (50) (50) (50) Pars Distalis, Angiectasis 14 [2.1] 30 [2.0] 16 [2.1] 15 [2.2] Pars Distalis, Cyst 6 [2.4] 3 [1.3] 6 [1.8] 5 [2.0] Pars Distalis, Hyperplasia, Focal 9 [2.1] 8 [2.0] 9 [1.8] 13 [2.3] Pars Distalis, Hyperplasia, Multifocal 1 [3.0] Pars Intermedia, Cyst 1 [1.0] Thyroid Gland (50) (50) (50) (50) Ultimobranchial Cyst 3 [1.7] 1 [1.0] 2 [1.5] C-Cell, Hyperplasia 8 [2.4] 2 [2.0] 9 [1.8] 4 [2.3] Follicle, Cyst 1 [1.0] 2 [2.0] 4 [1.0] 1 [1.0] Follicular Cell, Hyperplasia 1 [3.0] ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Coagulating Gland (1) (2) Inflammation 1 [4.0] Penis (1) Fibrosis 1 [2.0] Preputial Gland (50) (50) (50) (50) Cyst 4 [2.5] 3 [1.7] Inflammation, Chronic 5 [2.0] 5 [1.4] 4 [2.0] 4 [1.8] Prostate (50) (50) (50) (50) Inflammation, Chronic 31 [2.0] 28 [1.8] 27 [2.0] 26 [2.1] Testes (50) (50) (50) (50) Bilateral, Germinal Epithelium, Atrophy 1 [4.0] 2 [3.0] Germinal Epithelium, Atrophy 1 [1.0] 1 [3.0] ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Hyperplasia 7 [2.4] 7 [2.9] 4 [2.5] 9 [2.7] 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 9 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Lymph Node (21) (17) (10) (18) Deep Cervical, Hyperplasia, Lymphoid 1 [3.0] 1 [4.0] Deep Cervical, Inflammation, Granulomatous 1 [2.0] Mediastinal, Hyperplasia, Lymphoid 9 [2.0] 9 [2.0] 10 [2.2] 15 [2.0] Mediastinal, Inflammation, Granulomatous 1 [3.0] Pancreatic, Hyperplasia, Lymphoid 2 [2.0] 4 [2.0] 1 [2.0] 1 [2.0] Lymph Node, Mesenteric (50) (50) (50) (50) Hyperplasia, Lymphoid 7 [2.3] 3 [2.0] 4 [2.0] 9 [2.1] Spleen (50) (50) (50) (50) Fibrosis 1 [2.0] 2 [1.5] 2 [2.0] 2 [2.0] Hematopoietic Cell Proliferation 11 [1.5] 12 [2.0] 17 [1.5] 20 [1.7] Hemorrhage 2 [2.5] Necrosis 2 [3.0] Capsule, Fibrosis 1 [1.0] 7 [1.3] 12 [1.5] 30 [1.8] Lymphoid Follicle, Hyperplasia 1 [2.0] 1 [2.0] ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) Cyst 23 [1.8] 18 [1.7] 20 [1.8] 20 [1.9] Hyperplasia 1 [2.0] 1 [1.0] Skin (50) (50) (50) (50) Hyperkeratosis 1 [2.0] Inflammation, Chronic 5 [2.6] 1 [2.0] Lip, Inflammation 1 [4.0] Subcutaneous Tissue, Mineralization 1 [2.0] ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Cyst 1 Cranium, Osteopetrosis 1 [2.0] ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Compression 7 [3.0] 10 [2.0] 9 [2.2] 6 [2.3] Hemorrhage 1 [3.0] 2 [1.5] ____________________________________________________________________________________________________________________________________ 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: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 3 [1.7] 4 [1.5] 3 [1.3] 7 [1.9] Foreign Body 1 [2.0] 2 [2.0] Hemorrhage 1 [2.0] Infiltration Cellular, Histiocyte 28 [1.1] 29 [1.0] 36 [1.1] 26 [1.0] Inflammation, Chronic 29 [1.1] 23 [1.0] 36 [1.0] 30 [1.2] Inflammation, Suppurative 1 [3.0] Necrosis 1 [3.0] 1 [2.0] Alveolar Epithelium, Hyperplasia 7 [2.0] 9 [2.2] 4 [2.3] 6 [2.2] Mediastinum, Inflammation, Granulomatous 1 [3.0] Nose (50) (50) (50) (50) Foreign Body 7 [2.0] 4 [1.0] 12 [1.7] 7 [1.7] Inflammation, Chronic 12 [2.0] 3 [1.3] 20 [1.7] 15 [1.9] Pleura (1) Inflammation, Granulomatous 1 [3.0] Trachea (50) (50) (50) (50) Foreign Body 1 [2.0] Inflammation 1 [3.0] 1 [2.0] Necrosis 1 [2.0] Perforation 1 [2.0] ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (49) (48) (48) Cataract 1 [2.0] 3 [2.7] 4 [2.8] 3 [2.7] Inflammation, Chronic 1 [4.0] 1 [2.0] 1 [4.0] Phthisis Bulbi 1 Anterior Chamber, Inflammation, Acute 1 [2.0] Bilateral, Anterior Chamber, Inflammation, Acute 1 [2.0] Retina, Degeneration 1 [2.0] 2 [3.0] 4 [3.5] 3 [3.7] Harderian Gland (50) (50) (50) (50) Hyperplasia 1 [2.0] 1 [2.0] Inflammation, Chronic 2 [2.0] 3 [1.0] 1 [1.0] 4 [1.0] Pigmentation 2 [2.0] 1 [2.0] 1 [2.0] 3 [2.0] ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Cyst 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 11 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18 Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 03/25/05 Route: GAVAGE METHYLENE BLUE TRIHYDRATE Time: 10:16:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Hydronephrosis 1 [3.0] 2 [2.5] Infarct 2 [1.5] Nephropathy 35 [1.7] 39 [1.8] 33 [1.3] 34 [1.3] Urethra (1) Inflammation 1 [3.0] Urinary Bladder (50) (50) (50) (49) Hemorrhage 1 [2.0] 1 [2.0] Hyperplasia 1 [3.0] Inflammation, Chronic 2 [3.0] 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 12 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------