TDMS Study 91005-07 Pathology Tables
NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 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 Page 1 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ 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 (2%) Intestine Large, Colon (50) (48) (49) (48) Cyst 1 (2%) Intestine Small, Duodenum (49) (48) (49) (48) Ectopic Tissue 1 (2%) Liver (50) (49) (50) (50) Basophilic Focus 37 (74%) 34 (69%) 38 (76%) 40 (80%) Clear Cell Focus 8 (16%) 5 (10%) 9 (18%) 8 (16%) Degeneration, Cystic 1 (2%) 1 (2%) 1 (2%) Eosinophilic Focus 3 (6%) 2 (4%) Hepatodiaphragmatic Nodule 7 (14%) 4 (8%) 7 (14%) 4 (8%) Inflammation, Chronic 6 (12%) 4 (8%) 4 (8%) 5 (10%) Necrosis, Focal 1 (2%) 1 (2%) Bile Duct, Hyperplasia 7 (14%) 5 (10%) 6 (12%) 2 (4%) Centrilobular, Necrosis 2 (4%) 1 (2%) Hepatocyte, Vacuolization Cytoplasmic 4 (8%) 4 (8%) Mesentery (17) (14) (12) (8) Accessory Spleen 1 (7%) Fat, Necrosis 17 (100%) 14 (100%) 11 (92%) 8 (100%) Oral Mucosa (2) (1) Pharyngeal, Cyst 1 (50%) 1 (100%) Pancreas (49) (48) (48) (49) Atrophy 26 (53%) 20 (42%) 23 (48%) 23 (47%) Inflammation 1 (2%) Acinus, Hyperplasia, Focal 3 (6%) 1 (2%) 2 (4%) 1 (2%) Salivary Glands (50) (49) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Inflammation 1 (2%) Stomach, Forestomach (50) (49) (49) (49) Edema 2 (4%) 3 (6%) 1 (2%) Erosion 1 (2%) Inflammation, Chronic Active 1 (2%) 2 (4%) Ulcer 4 (8%) 3 (6%) 1 (2%) 1 (2%) Epithelium, Hyperplasia 2 (4%) 2 (4%) 2 (4%) 3 (6%) Stomach, Glandular (50) (49) (48) (49) Edema 2 (4%) 1 (2%) 1 (2%) Erosion 2 (4%) 2 (4%) Ulcer 2 (4%) 1 (2%) 1 (2%) Tongue (1) (1) (1) (1) Cyst 1 (100%) Hyperplasia 1 (100%) 1 (100%) Inflammation 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (49) (50) (50) Cardiomyopathy 36 (72%) 41 (84%) 36 (72%) 32 (64%) Thrombosis 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (49) (50) (50) Accessory Adrenal Cortical Nodule 9 (18%) 7 (14%) 8 (16%) 12 (24%) Degeneration, Fatty 11 (22%) 13 (27%) 13 (26%) 8 (16%) Hyperplasia, Focal 5 (10%) 8 (16%) 8 (16%) 6 (12%) Hypertrophy, Focal 12 (24%) 11 (22%) 13 (26%) 7 (14%) Necrosis 2 (4%) 1 (2%) Adrenal Medulla (50) (49) (50) (50) Hyperplasia 1 (2%) 2 (4%) 1 (2%) Islets, Pancreatic (49) (48) (48) (49) Hyperplasia 13 (27%) 15 (31%) 15 (31%) 15 (31%) Metaplasia, Hepatocyte 2 (4%) Pituitary Gland (50) (49) (50) (50) Pars Distalis, Angiectasis 28 (56%) 27 (55%) 29 (58%) 21 (42%) Pars Distalis, Cyst 21 (42%) 19 (39%) 16 (32%) 23 (46%) Pars Distalis, Hyperplasia, Focal 5 (10%) 8 (16%) 6 (12%) 6 (12%) Pars Intermedia, Cyst 1 (2%) Thyroid Gland (50) (49) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Ultimobranchial Cyst 2 (4%) 1 (2%) C-Cell, Hyperplasia 10 (20%) 11 (22%) 7 (14%) 5 (10%) Follicle, Cyst 2 (4%) 1 (2%) 2 (4%) 4 (8%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (48) (50) (50) Cyst 4 (8%) 7 (15%) 4 (8%) 6 (12%) Inflammation, Chronic 1 (2%) 5 (10%) 2 (4%) 4 (8%) Ovary (50) (49) (50) (50) Cyst 11 (22%) 4 (8%) 9 (18%) 10 (20%) Uterus (50) (49) (50) (50) Cyst 1 (2%) 3 (6%) 2 (4%) 3 (6%) Hemorrhage 1 (2%) 1 (2%) Hydrometra 1 (2%) 4 (8%) 2 (4%) 1 (2%) Cervix, Cyst 1 (2%) Endometrium, Hyperplasia, Cystic 4 (8%) 1 (2%) 2 (4%) Vagina (1) Cyst 1 (100%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (49) (50) (50) Hyperplasia 8 (16%) 8 (16%) 9 (18%) 6 (12%) Lymph Node (15) (8) (11) (3) Mediastinal, Congestion 1 (7%) Mediastinal, Hyperplasia, Lymphoid 5 (33%) 7 (88%) 8 (73%) 2 (67%) Pancreatic, Hyperplasia, Lymphoid 1 (7%) 1 (9%) 1 (33%) Lymph Node, Mesenteric (49) (49) (50) (50) Hyperplasia, Lymphoid 1 (2%) 1 (2%) Spleen (49) (48) (49) (49) Fibrosis 2 (4%) Hematopoietic Cell Proliferation 3 (6%) 5 (10%) 7 (14%) 8 (16%) Necrosis 1 (2%) Capsule, Fibrosis 8 (16%) 17 (35%) 12 (24%) 20 (41%) Lymphoid Follicle, Atrophy 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Lymphoid Follicle, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (49) (50) (50) Cyst 2 (4%) 1 (2%) Galactocele 1 (2%) 1 (2%) 1 (2%) Hyperplasia 18 (36%) 19 (39%) 9 (18%) 7 (14%) Hyperplasia, Atypical 3 (6%) 3 (6%) 1 (2%) Duct, Dilatation 31 (62%) 28 (57%) 29 (58%) 24 (48%) Duct, Hyperplasia 2 (4%) 1 (2%) Skin (50) (49) (50) (50) Inflammation, Chronic 2 (4%) Inflammation, Chronic Active 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (49) (50) (50) Inflammation 1 (2%) Cranium, Osteopetrosis 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (49) (50) (50) Compression 3 (6%) 8 (16%) 6 (12%) 5 (10%) Hemorrhage 1 (2%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) (50) (50) Congestion 5 (10%) 2 (4%) 5 (10%) 8 (16%) Foreign Body 1 (2%) Infiltration Cellular, Histiocyte 41 (82%) 37 (76%) 39 (78%) 38 (76%) Inflammation, Chronic 29 (58%) 33 (67%) 29 (58%) 33 (66%) Inflammation, Suppurative 1 (2%) Necrosis 1 (2%) Alveolar Epithelium, Hyperplasia 1 (2%) 4 (8%) 3 (6%) 2 (4%) Nose (50) (49) (50) (50) Foreign Body 4 (8%) 3 (6%) 1 (2%) 3 (6%) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Inflammation, Chronic 8 (16%) 7 (14%) 9 (18%) 6 (12%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (49) (50) (50) Cataract 1 (2%) 2 (4%) 5 (10%) 3 (6%) Inflammation, Chronic 2 (4%) Anterior Chamber, Inflammation 1 (2%) Cornea, Inflammation, Chronic 1 (2%) 1 (2%) 2 (4%) Retina, Degeneration 2 (4%) 2 (4%) 4 (8%) 2 (4%) Harderian Gland (50) (49) (50) (50) Inflammation, Chronic 3 (6%) 3 (6%) 3 (6%) 4 (8%) Pigmentation 2 (4%) 2 (4%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (49) (50) (50) Cyst 1 (2%) 1 (2%) Infarct 1 (2%) 2 (4%) 2 (4%) Nephropathy 14 (28%) 15 (31%) 21 (42%) 16 (32%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ 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 (4%) Intestine Large, Colon (50) (50) (50) (50) Inflammation 1 (2%) Intestine Large, Cecum (49) (50) (49) (47) Inflammation, Chronic 1 (2%) Intestine Small, Duodenum (50) (50) (50) (48) Ectopic Tissue 1 (2%) 1 (2%) Ulcer 1 (2%) Intestine Small, Ileum (48) (50) (49) (48) Hyperplasia, Lymphoid 1 (2%) Liver (50) (50) (50) (50) Basophilic Focus 5 (10%) 6 (12%) 8 (16%) 6 (12%) Clear Cell Focus 14 (28%) 13 (26%) 16 (32%) 12 (24%) Degeneration, Cystic 5 (10%) 3 (6%) 2 (4%) 1 (2%) Eosinophilic Focus 5 (10%) 1 (2%) 4 (8%) 3 (6%) Hepatodiaphragmatic Nodule 9 (18%) 2 (4%) 3 (6%) 4 (8%) Inflammation, Chronic 1 (2%) 1 (2%) Necrosis, Focal 1 (2%) 1 (2%) Bile Duct, Hyperplasia 41 (82%) 35 (70%) 38 (76%) 37 (74%) Centrilobular, Necrosis 2 (4%) 1 (2%) 2 (4%) Hepatocyte, Vacuolization Cytoplasmic 5 (10%) 1 (2%) 2 (4%) 3 (6%) Serosa, Inflammation 1 (2%) Mesentery (16) (11) (9) (12) Accessory Spleen 1 (8%) Fibrosis 1 (6%) Fat, Necrosis 14 (88%) 9 (82%) 8 (89%) 7 (58%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ 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 (50%) Pharyngeal, Inflammation 2 (50%) Pancreas (50) (50) (50) (50) Atrophy 43 (86%) 31 (62%) 35 (70%) 32 (64%) Atrophy, Focal 1 (2%) Cyst 1 (2%) Inflammation, Chronic 1 (2%) Acinus, Hyperplasia, Focal 4 (8%) 6 (12%) 15 (30%) 12 (24%) Salivary Glands (50) (50) (50) (50) Hyperplasia 1 (2%) Stomach, Forestomach (50) (50) (50) (50) Edema 6 (12%) 1 (2%) 2 (4%) Erosion 3 (6%) 1 (2%) Ulcer 4 (8%) 1 (2%) 2 (4%) 2 (4%) Epithelium, Hyperplasia 4 (8%) 3 (6%) 3 (6%) Stomach, Glandular (50) (50) (50) (50) Edema 1 (2%) 2 (4%) Erosion 4 (8%) 2 (4%) 1 (2%) 1 (2%) Hyperplasia 1 (2%) Inflammation 1 (2%) Mineralization 1 (2%) Ulcer 2 (4%) 1 (2%) 2 (4%) 1 (2%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) Cardiomyopathy 47 (94%) 46 (92%) 47 (94%) 45 (90%) Mineralization 1 (2%) Thrombosis 1 (2%) 1 (2%) Pericardium, Inflammation, Granulomatous 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 23 (46%) 23 (46%) 28 (56%) 25 (50%) Degeneration, Fatty 7 (14%) 6 (12%) 7 (14%) 2 (4%) Hyperplasia, Focal 6 (12%) 5 (10%) 5 (10%) 5 (10%) Hypertrophy, Focal 6 (12%) 5 (10%) 9 (18%) 8 (16%) Necrosis 1 (2%) 1 (2%) Adrenal Medulla (50) (50) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hyperplasia 7 (14%) 12 (24%) 8 (16%) 2 (4%) Thrombosis 1 (2%) Islets, Pancreatic (50) (50) (50) (50) Hyperplasia 13 (26%) 13 (26%) 17 (34%) 26 (52%) Metaplasia, Hepatocyte 1 (2%) Pituitary Gland (50) (50) (50) (50) Pars Distalis, Angiectasis 14 (28%) 30 (60%) 16 (32%) 15 (30%) Pars Distalis, Cyst 6 (12%) 3 (6%) 6 (12%) 5 (10%) Pars Distalis, Hyperplasia, Focal 9 (18%) 8 (16%) 9 (18%) 13 (26%) Pars Distalis, Hyperplasia, Multifocal 1 (2%) Pars Intermedia, Cyst 1 (2%) Thyroid Gland (50) (50) (50) (50) Ultimobranchial Cyst 3 (6%) 1 (2%) 2 (4%) C-Cell, Hyperplasia 8 (16%) 2 (4%) 9 (18%) 4 (8%) Follicle, Cyst 1 (2%) 2 (4%) 4 (8%) 1 (2%) Follicular Cell, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Coagulating Gland (1) (2) Inflammation 1 (50%) Penis (1) Fibrosis 1 (100%) Preputial Gland (50) (50) (50) (50) Cyst 4 (8%) 3 (6%) Inflammation, Chronic 5 (10%) 5 (10%) 4 (8%) 4 (8%) Prostate (50) (50) (50) (50) Inflammation, Chronic 31 (62%) 28 (56%) 27 (54%) 26 (52%) Testes (50) (50) (50) (50) Bilateral, Germinal Epithelium, Atrophy 1 (2%) 2 (4%) Germinal Epithelium, Atrophy 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Hyperplasia 7 (14%) 7 (14%) 4 (8%) 9 (18%) a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ 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 (6%) 1 (10%) Deep Cervical, Inflammation, Granulomatous 1 (5%) Mediastinal, Hyperplasia, Lymphoid 9 (43%) 9 (53%) 10 (100%) 15 (83%) Mediastinal, Inflammation, Granulomatous 1 (5%) Pancreatic, Hyperplasia, Lymphoid 2 (10%) 4 (24%) 1 (10%) 1 (6%) Lymph Node, Mesenteric (50) (50) (50) (50) Hyperplasia, Lymphoid 7 (14%) 3 (6%) 4 (8%) 9 (18%) Spleen (50) (50) (50) (50) Fibrosis 1 (2%) 2 (4%) 2 (4%) 2 (4%) Hematopoietic Cell Proliferation 11 (22%) 12 (24%) 17 (34%) 20 (40%) Hemorrhage 2 (4%) Necrosis 2 (4%) Capsule, Fibrosis 1 (2%) 7 (14%) 12 (24%) 30 (60%) Lymphoid Follicle, Hyperplasia 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) Cyst 23 (46%) 18 (36%) 20 (40%) 20 (40%) Hyperplasia 1 (2%) 1 (2%) Skin (50) (50) (50) (50) Hyperkeratosis 1 (2%) Inflammation, Chronic 5 (10%) 1 (2%) Lip, Inflammation 1 (2%) Subcutaneous Tissue, Mineralization 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Cyst 1 (2%) Cranium, Osteopetrosis 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Compression 7 (14%) 10 (20%) 9 (18%) 6 (12%) Hemorrhage 1 (2%) 2 (4%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ 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 (6%) 4 (8%) 3 (6%) 7 (14%) Foreign Body 1 (2%) 2 (4%) Hemorrhage 1 (2%) Infiltration Cellular, Histiocyte 28 (56%) 29 (58%) 36 (72%) 26 (52%) Inflammation, Chronic 29 (58%) 23 (46%) 36 (72%) 30 (60%) Inflammation, Suppurative 1 (2%) Necrosis 1 (2%) 1 (2%) Alveolar Epithelium, Hyperplasia 7 (14%) 9 (18%) 4 (8%) 6 (12%) Mediastinum, Inflammation, Granulomatous 1 (2%) Nose (50) (50) (50) (50) Foreign Body 7 (14%) 4 (8%) 12 (24%) 7 (14%) Inflammation, Chronic 12 (24%) 3 (6%) 20 (40%) 15 (30%) Pleura (1) Inflammation, Granulomatous 1 (100%) Trachea (50) (50) (50) (50) Foreign Body 1 (2%) Inflammation 1 (2%) 1 (2%) Necrosis 1 (2%) Perforation 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (49) (48) (48) Cataract 1 (2%) 3 (6%) 4 (8%) 3 (6%) Inflammation, Chronic 1 (2%) 1 (2%) 1 (2%) Phthisis Bulbi 1 (2%) Anterior Chamber, Inflammation, Acute 1 (2%) Bilateral, Anterior Chamber, Inflammation, Acute 1 (2%) Retina, Degeneration 1 (2%) 2 (4%) 4 (8%) 3 (6%) Harderian Gland (50) (50) (50) (50) Hyperplasia 1 (2%) 1 (2%) Inflammation, Chronic 2 (4%) 3 (6%) 1 (2%) 4 (8%) Pigmentation 2 (4%) 1 (2%) 1 (2%) 3 (6%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Cyst 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 91005-07 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 03/25/05 Route: GAVAGE Time: 10:00:58 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Hydronephrosis 1 (2%) 2 (4%) Infarct 2 (4%) Nephropathy 35 (70%) 39 (78%) 33 (66%) 34 (68%) Urethra (1) Inflammation 1 (100%) Urinary Bladder (50) (50) (50) (49) Hemorrhage 1 (2%) 1 (2%) Hyperplasia 1 (2%) Inflammation, Chronic 2 (4%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 12 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------