TDMS Study 91005-08 Pathology Tables
NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 FINAL #1; REVISION #1 MICE 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: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 9 5 2 6 Moribund Sacrifice 7 4 5 1 Accidently Killed 1 Dosing Accident 1 1 Survivors Terminal Sacrifice 29 40 41 41 Natural Death 2 1 2 Moribund Sacrifice 2 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Foreign Body 1 (2%) Inflammation 1 (2%) Perforation 1 (2%) Gallbladder (42) (45) (47) (44) Cyst 2 (5%) 1 (2%) 2 (5%) Intestine Large, Rectum (48) (48) (50) (46) Artery, Inflammation, Chronic, Focal 1 (2%) Intestine Large, Cecum (43) (46) (47) (44) Edema 1 (2%) Lymphoid Tissue, Hyperplasia, Lymphoid 1 (2%) Intestine Small, Duodenum (43) (45) (47) (42) Epithelium, Hyperplasia, Focal 1 (2%) Intestine Small, Jejunum (43) (45) (47) (43) Epithelium, Hyperplasia, Focal 1 (2%) Lymphoid Tissue, Hyperplasia 1 (2%) Liver (50) (50) (50) (50) Angiectasis, Focal 2 (4%) Basophilic Focus 1 (2%) 3 (6%) Clear Cell Focus 3 (6%) 3 (6%) 4 (8%) 2 (4%) Congestion 1 (2%) 2 (4%) 1 (2%) 1 (2%) Eosinophilic Focus 1 (2%) 1 (2%) 3 (6%) 1 (2%) Fibrosis, Focal 1 (2%) Hematopoietic Cell Proliferation 4 (8%) 1 (2%) 6 (12%) 2 (4%) Hemorrhage 1 (2%) 1 (2%) Hepatodiaphragmatic Nodule 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Infarct 1 (2%) Infiltration Cellular, Mixed Cell 11 (22%) 12 (24%) 12 (24%) 15 (30%) Mixed Cell Focus 2 (4%) 1 (2%) 1 (2%) Bile Duct, Cyst 1 (2%) Hepatocyte, Necrosis, Focal 3 (6%) 3 (6%) 1 (2%) Hepatocyte, Vacuolization Cytoplasmic 12 (24%) 11 (22%) 8 (16%) 15 (30%) Kupffer Cell, Pigmentation 1 (2%) 1 (2%) Mesentery (18) (14) (15) (13) Hemorrhage 1 (7%) 1 (8%) Infiltration Cellular, Lymphoid 1 (7%) Artery, Inflammation, Chronic, Focal 1 (6%) 1 (7%) 1 (7%) Fat, Necrosis, Focal 16 (89%) 12 (86%) 13 (87%) 4 (31%) Pancreas (46) (46) (49) (49) Acinus, Atrophy, Diffuse 1 (2%) Acinus, Atrophy, Focal 1 (2%) 1 (2%) 1 (2%) Acinus, Cytoplasmic Alteration 1 (2%) Duct, Cyst 2 (4%) 2 (4%) 2 (4%) Salivary Glands (50) (50) (50) (49) Hyperplasia, Lymphoid 1 (2%) Stomach, Forestomach (50) (50) (50) (49) Diverticulum 1 (2%) 1 (2%) 3 (6%) Inflammation, Focal 1 (2%) 1 (2%) Ulcer 2 (4%) 3 (6%) 1 (2%) Epithelium, Hyperplasia 2 (4%) 2 (4%) 2 (4%) 1 (2%) Stomach, Glandular (45) (47) (50) (46) Cyst 1 (2%) 1 (2%) Epithelium, Cytoplasmic Alteration, Focal 1 (2%) Epithelium, Hyperplasia 1 (2%) Tooth (2) (10) (3) (3) Dysplasia 2 (100%) 10 (100%) 3 (100%) 3 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (1) Aneurysm 1 (100%) Heart (50) (50) (50) (50) Cardiomyopathy 1 (2%) 1 (2%) Infiltration Cellular, Mixed Cell 1 (2%) Mineralization, Focal 1 (2%) Thrombosis 1 (2%) Artery, Inflammation, Chronic 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 2 (4%) 2 (4%) Angiectasis 1 (2%) Cytoplasmic Alteration, Focal 1 (2%) Degeneration, Cystic 1 (2%) Hyperplasia, Focal 1 (2%) Infiltration Cellular, Mixed Cell 1 (2%) Adrenal Medulla (50) (50) (49) (50) Hyperplasia, Focal 1 (2%) Parathyroid Gland (48) (48) (46) (49) Cyst 1 (2%) 1 (2%) 1 (2%) 1 (2%) Pituitary Gland (46) (49) (48) (47) Angiectasis 2 (4%) 1 (2%) Cyst 1 (2%) 1 (2%) Pars Distalis, Cytoplasmic Alteration, Focal 1 (2%) 4 (8%) 1 (2%) 2 (4%) Pars Distalis, Hyperplasia, Focal 1 (2%) 1 (2%) 1 (2%) 1 (2%) Thyroid Gland (46) (50) (49) (47) Cyst 1 (2%) 1 (2%) Inflammation, Chronic, Focal 1 (2%) 1 (2%) 1 (2%) C-Cell, Hyperplasia 1 (2%) 1 (2%) Follicle, Degeneration, Cystic, Focal 17 (37%) 15 (30%) 28 (57%) 23 (49%) Follicular Cell, Hyperplasia, Focal 5 (11%) 2 (4%) 4 (8%) 5 (11%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (3) (3) Pelvic, Fibrosis 1 (33%) ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (48) (50) (46) (48) Degeneration, Cystic 1 (2%) 1 (2%) Ovary (47) (48) (49) (48) Angiectasis 3 (6%) 2 (4%) 2 (4%) Cyst 11 (23%) 12 (25%) 16 (33%) 13 (27%) Hemorrhage 1 (2%) 1 (2%) Pigmentation, Focal 1 (2%) Thrombosis 3 (6%) 3 (6%) Bilateral, Cyst 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Interstitial Cell, Hyperplasia 1 (2%) Uterus (50) (50) (50) (50) Angiectasis 1 (2%) 1 (2%) 1 (2%) Hemorrhage 1 (2%) Inflammation, Chronic 1 (2%) Inflammation, Suppurative 1 (2%) Endometrium, Hyperplasia, Cystic 48 (96%) 45 (90%) 49 (98%) 48 (96%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (49) (50) Hyperplasia 10 (20%) 4 (8%) 9 (18%) 4 (8%) Lymph Node (7) (5) (10) (10) Iliac, Angiectasis 1 (14%) Iliac, Hyperplasia, Lymphoid 1 (14%) 2 (20%) 2 (20%) Mediastinal, Hyperplasia, Lymphoid 2 (29%) 1 (10%) Mediastinal, Inflammation 1 (10%) Pancreatic, Hyperplasia, Lymphoid 1 (20%) 1 (10%) 1 (10%) Renal, Hyperplasia, Lymphoid 1 (14%) 1 (10%) 1 (10%) Lymph Node, Mandibular (48) (49) (48) (46) Hemorrhage 1 (2%) Hyperplasia, Lymphoid 9 (19%) 11 (22%) 12 (25%) 16 (35%) Hyperplasia, Mast Cell 1 (2%) Lymph Node, Mesenteric (46) (49) (49) (48) Ectasia 1 (2%) 2 (4%) Hemorrhage 1 (2%) 2 (4%) 2 (4%) 1 (2%) Hyperplasia, Histiocytic 1 (2%) Hyperplasia, Lymphoid 6 (13%) 7 (14%) 10 (20%) 8 (17%) Spleen (47) (47) (49) (50) Angiectasis, Focal 1 (2%) Congestion 2 (4%) Fibrosis, Focal 1 (2%) 1 (2%) Hematopoietic Cell Proliferation 23 (49%) 21 (45%) 31 (63%) 40 (80%) Hyperplasia, Lymphoid 17 (36%) 15 (32%) 17 (35%) 11 (22%) Thymus (43) (47) (44) (49) Hyperplasia, Lymphoid 8 (19%) 13 (28%) 11 (25%) 14 (29%) Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (50) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM - CONT Subcutaneous Tissue, Edema 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Hyperostosis 5 (10%) 5 (10%) 4 (8%) 5 (10%) Vertebra, Hypertrophy, Focal 3 (6%) 2 (4%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (49) Compression, Focal 1 (2%) 1 (2%) Artery, Meninges, Inflammation, Chronic 1 (2%) Spinal Cord (1) (2) (1) (1) Demyelination, Focal 1 (50%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 1 (2%) Foreign Body 1 (2%) 1 (2%) Hemorrhage 1 (2%) 1 (2%) Hyperplasia, Histiocytic 1 (2%) 1 (2%) Hyperplasia, Lymphoid 1 (2%) Infiltration Cellular, Polymorphonuclear 1 (2%) Infiltration Cellular, Mixed Cell 1 (2%) Inflammation 1 (2%) 1 (2%) Metaplasia, Focal, Osseous 1 (2%) Alveolar Epithelium, Hyperplasia, Focal 2 (4%) 1 (2%) 1 (2%) Mediastinum, Foreign Body 1 (2%) 1 (2%) Mediastinum, Inflammation 1 (2%) 1 (2%) Serosa, Fibrosis 1 (2%) Nose (50) (50) (50) (50) Inflammation 3 (6%) 7 (14%) 11 (22%) Nasolacrimal Duct, Hyperplasia, Focal 1 (2%) Nasolacrimal Duct, Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM - CONT Eye (43) (48) (47) (47) Atrophy 1 (2%) Cataract 1 (2%) Anterior Chamber, Inflammation 1 (2%) Artery, Retrobulbar, Inflammation, Chronic, Focal 1 (2%) Cornea, Inflammation 1 (2%) 1 (2%) 1 (2%) 1 (2%) Cornea, Necrosis, Focal 1 (2%) Harderian Gland (49) (50) (50) (50) Epithelium, Hyperplasia 2 (4%) 1 (2%) 3 (6%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (50) (49) (50) Hemorrhage 1 (2%) Hyperplasia, Lymphoid 1 (2%) Infarct 1 (2%) 2 (4%) 2 (4%) Metaplasia, Focal, Osseous 2 (4%) 1 (2%) 1 (2%) Nephropathy 6 (13%) 5 (10%) 9 (18%) 5 (10%) Bilateral, Infarct 1 (2%) Capsule, Fibrosis, Focal 1 (2%) Renal Tubule, Accumulation, Hyaline Droplet 2 (4%) 2 (4%) Renal Tubule, Cyst 1 (2%) 3 (6%) Urinary Bladder (45) (47) (49) (48) Hyperplasia, Lymphoid 1 (2%) Inflammation 1 (2%) Transitional Epithelium, Hyperplasia 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Natural Death 11 6 5 3 Moribund Sacrifice 4 4 7 4 Accidently Killed 1 Dosing Accident 1 2 Survivors Terminal Sacrifice 35 38 38 41 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Foreign Body 1 (2%) 1 (2%) Inflammation 1 (2%) 1 (2%) 1 (2%) Perforation 1 (2%) 1 (2%) Intestine Large, Cecum (45) (46) (46) (47) Edema 1 (2%) 1 (2%) Inflammation, Chronic, Focal 1 (2%) Intestine Small, Duodenum (42) (46) (46) (46) Epithelium, Cyst 1 (2%) Intestine Small, Jejunum (45) (45) (47) (47) Inflammation 1 (2%) Lymphoid Tissue, Hyperplasia 1 (2%) Peyer's Patch, Hyperplasia, Lymphoid 1 (2%) Liver (50) (50) (50) (49) Basophilic Focus 1 (2%) Clear Cell Focus 20 (40%) 19 (38%) 22 (44%) 16 (33%) Congestion 1 (2%) Cyst 1 (2%) 1 (2%) Eosinophilic Focus 2 (4%) 2 (4%) 2 (4%) Fibrosis, Focal 1 (2%) Hematopoietic Cell Proliferation 1 (2%) 2 (4%) Hemorrhage 1 (2%) Hepatodiaphragmatic Nodule 1 (2%) 1 (2%) Infarct 1 (2%) Infiltration Cellular, Mixed Cell 3 (6%) 1 (2%) 2 (4%) 6 (12%) Mixed Cell Focus 3 (6%) 1 (2%) Thrombosis 2 (4%) 1 (2%) 1 (2%) Bile Duct, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Hepatocyte, Necrosis, Focal 2 (4%) 2 (4%) 2 (4%) 4 (8%) Hepatocyte, Syncytial Alteration, Focal 1 (2%) Hepatocyte, Vacuolization Cytoplasmic 29 (58%) 19 (38%) 32 (64%) 23 (47%) Hepatocyte, Centrilobular, Necrosis 1 (2%) Mesentery (5) (11) (5) (4) Inflammation 1 (9%) 1 (25%) Fat, Necrosis, Focal 4 (80%) 7 (64%) 4 (80%) Pancreas (48) (50) (49) (48) Acinus, Atrophy, Diffuse 1 (2%) Acinus, Atrophy, Focal 1 (2%) 1 (2%) 2 (4%) 1 (2%) Acinus, Cytoplasmic Alteration 1 (2%) 1 (2%) Acinus, Inflammation 1 (2%) Duct, Cyst 1 (2%) Stomach, Forestomach (50) (50) (50) (48) Ulcer 3 (6%) 1 (2%) Epithelium, Hyperplasia 3 (6%) 2 (4%) 3 (6%) 2 (4%) Stomach, Glandular (47) (47) (47) (48) Erosion 2 (4%) 1 (2%) 2 (4%) 1 (2%) Ulcer 1 (2%) Tooth (43) (37) (33) (35) Dysplasia 43 (100%) 37 (100%) 33 (100%) 35 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) Infiltration Cellular, Mixed Cell 1 (2%) 1 (2%) 1 (2%) Mineralization, Focal 1 (2%) 1 (2%) Artery, Inflammation, Chronic 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (48) (50) (50) (48) Accessory Adrenal Cortical Nodule 1 (2%) 1 (2%) Cytoplasmic Alteration, Focal 4 (8%) 5 (10%) 5 (10%) Degeneration, Cystic 1 (2%) 1 (2%) Hyperplasia, Focal 1 (2%) Hypertrophy 1 (2%) Hypertrophy, Focal 1 (2%) Inflammation 1 (2%) Adrenal Medulla (48) (50) (50) (48) Hyperplasia, Focal 2 (4%) 1 (2%) 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Islets, Pancreatic (50) (50) (49) (48) Hyperplasia 17 (34%) 17 (34%) 7 (14%) 13 (27%) Parathyroid Gland (46) (50) (48) (46) Cyst 3 (6%) 3 (6%) 2 (4%) Pituitary Gland (50) (49) (49) (50) Cyst 3 (6%) 1 (2%) 1 (2%) 3 (6%) Pars Distalis, Hyperplasia, Focal 1 (2%) Thyroid Gland (50) (50) (49) (48) Follicle, Degeneration, Cystic, Focal 6 (12%) 12 (24%) 11 (22%) 7 (15%) Follicular Cell, Hyperplasia, Focal 14 (28%) 5 (10%) 11 (22%) 11 (23%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (1) (2) (1) Foreign Body 1 (100%) Abdominal, Fibrosis 2 (100%) Abdominal, Inflammation 1 (50%) Pelvic, Inflammation 1 (100%) ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Preputial Gland (50) (50) (50) (48) Degeneration, Cystic 11 (22%) 11 (22%) 16 (32%) 11 (23%) Inflammation, Chronic 2 (4%) 1 (2%) 2 (4%) 3 (6%) Prostate (49) (50) (50) (50) Inflammation 1 (2%) 1 (2%) 1 (2%) Epithelium, Hyperplasia 1 (2%) 1 (2%) 1 (2%) Seminal Vesicle (49) (50) (50) (49) Dilatation 2 (4%) 2 (4%) Epithelium, Hyperplasia 1 (2%) Testes (50) (50) (50) (50) Angiectasis 1 (2%) Atrophy 1 (2%) 1 (2%) Thrombosis 1 (2%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Hyperplasia 2 (4%) 3 (6%) 3 (6%) 2 (4%) Lymph Node (5) (3) (3) (6) a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Iliac, Hyperplasia, Lymphoid 1 (33%) Inguinal, Hyperplasia, Lymphoid 1 (20%) Mediastinal, Hemorrhage 1 (33%) Mediastinal, Hyperplasia, Lymphoid 1 (17%) Lymph Node, Mandibular (43) (46) (48) (47) Hemorrhage 1 (2%) Hyperplasia, Lymphoid 2 (5%) 1 (2%) 2 (4%) Lymph Node, Mesenteric (47) (50) (48) (48) Hematopoietic Cell Proliferation 1 (2%) Hemorrhage 3 (6%) Hyperplasia, Lymphoid 2 (4%) 2 (4%) 2 (4%) Spleen (49) (50) (49) (48) Atrophy 1 (2%) Fibrosis, Focal 1 (2%) Hematopoietic Cell Proliferation 14 (29%) 16 (32%) 25 (51%) 29 (60%) Hyperplasia, Lymphoid 7 (14%) 6 (12%) 2 (4%) 3 (6%) Hyperplasia, Mast Cell 1 (2%) Lymphoid Follicle, Necrosis 1 (2%) 1 (2%) Thymus (38) (47) (40) (44) Angiectasis 1 (2%) Hyperplasia, Lymphoid 1 (2%) Epithelial Cell, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (50) (50) (50) Cyst Epithelial Inclusion 1 (2%) Ulcer 2 (4%) Pinna, Inflammation, Focal 1 (2%) Subcutaneous Tissue, Edema 1 (2%) 1 (2%) 2 (4%) 1 (2%) Subcutaneous Tissue, Inflammation, Focal, Suppurative 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Hyperostosis 2 (4%) Vertebra, Fracture 1 (2%) Skeletal Muscle (4) (1) (1) Fibrosis, Focal 1 (25%) Inflammation 1 (25%) a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Compression, Focal 1 (2%) Spinal Cord (4) (4) (1) (2) Hemorrhage 2 (50%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Congestion 1 (2%) 1 (2%) 1 (2%) Hemorrhage 1 (2%) 1 (2%) Hyperplasia, Histiocytic 1 (2%) 3 (6%) 2 (4%) Inflammation 1 (2%) Thrombosis 1 (2%) Alveolar Epithelium, Hyperplasia, Focal 4 (8%) 3 (6%) 2 (4%) 4 (8%) Mediastinum, Foreign Body 1 (2%) Mediastinum, Inflammation, Suppurative 1 (2%) Mediastinum, Thrombosis 1 (2%) Nose (50) (50) (50) (50) Hyperplasia 1 (2%) Inflammation 1 (2%) 3 (6%) 3 (6%) 6 (12%) Nasolacrimal Duct, Hyperplasia, Focal 1 (2%) 1 (2%) Nasolacrimal Duct, Inflammation 3 (6%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (45) (49) (49) (47) Atrophy 1 (2%) Cataract 1 (2%) Cornea, Inflammation 2 (4%) 1 (2%) Cornea, Necrosis, Focal 1 (2%) Retrobulbar, Inflammation, Chronic, Focal 1 (2%) Harderian Gland (50) (50) (50) (50) Cyst 1 (2%) Inflammation 1 (2%) 1 (2%) Epithelium, Hyperplasia 2 (4%) 2 (4%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM a Number of animals examined microscopically at site and number of animals with lesion Page 12 NTP Experiment-Test: 91005-08 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC METHYLENE BLUE TRIHYDRATE Date: 06/02/05 Route: GAVAGE Time: 13:15:21 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 MG/KG 2.5 12.5 25 MG/KG MG/KG MG/KG ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Kidney (49) (49) (50) (48) Hydronephrosis 2 (4%) Hyperplasia, Lymphoid 1 (2%) Infarct 1 (2%) 1 (2%) Metaplasia, Focal, Osseous 3 (6%) 3 (6%) 4 (8%) Mineralization, Focal 1 (2%) Nephropathy 40 (82%) 44 (90%) 44 (88%) 43 (90%) Artery, Inflammation, Chronic 1 (2%) Renal Tubule, Accumulation, Hyaline Droplet 1 (2%) Renal Tubule, Cyst 4 (8%) 2 (4%) 3 (6%) 2 (4%) Renal Tubule, Hyperplasia, Atypical 1 (2%) Renal Tubule, Hyperplasia, Focal 3 (6%) 2 (4%) 1 (2%) 2 (4%) Renal Tubule, Pigmentation 1 (2%) Urethra (1) Inflammation, Chronic 1 (100%) Urinary Bladder (48) (50) (50) (48) Transitional Epithelium, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 13 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------