TDMS Study 92012-05 Pathology Tables
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
FINAL#1; REVISION #1
Facility: Southern Research Institute
Chemical CAS #: 693-98-1
Lock Date: 10/16/01
Cage Range: All
Reasons For Removal: 25019 Moribund Sacrifice 25020 Natural Death
25021 Terminal Sacrifice
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: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 60 60 60 60
Early Deaths
Natural Death 4 3 10 1
Moribund Sacrifice 6 8 12 7
Survivors
Terminal Sacrifice 40 39 28 41
Natural Death 1
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (48) (47) (44) (50)
Edema 1 (2%)
Intestine Small, Jejunum (47) (46) (44) (49)
Necrosis, Focal 1 (2%)
Liver (50) (49) (50) (50)
Angiectasis, Focal 2 (4%) 1 (2%) 2 (4%)
Basophilic Focus 42 (84%) 44 (90%) 43 (86%) 39 (78%)
Cholangiofibrosis 1 (2%)
Congestion 2 (4%) 1 (2%)
Congestion, Focal 1 (2%)
Degeneration, Cystic, Focal 1 (2%) 2 (4%)
Eosinophilic Focus 1 (2%)
Fatty Change 2 (4%) 1 (2%)
Hemorrhage 2 (4%) 2 (4%)
Hepatodiaphragmatic Nodule 6 (12%) 11 (22%) 14 (28%) 13 (26%)
Hyperplasia, Focal, Lymphoid 1 (2%) 1 (2%)
Infarct 2 (4%)
Infiltration Cellular, Mixed Cell 42 (84%) 44 (90%) 34 (68%) 38 (76%)
Inflammation, Granulomatous 18 (36%) 23 (47%) 22 (44%) 42 (84%)
Mixed Cell Focus 15 (30%) 14 (29%) 11 (22%) 26 (52%)
Necrosis, Focal 1 (2%) 1 (2%)
Bile Duct, Cholangiofibrosis, Focal 1 (2%)
Bile Duct, Cyst 2 (4%)
Bile Duct, Cyst, Multiple 1 (2%) 1 (2%)
Bile Duct, Hyperplasia 20 (40%) 29 (59%) 20 (40%) 40 (80%)
Hepatocyte, Necrosis, Focal 1 (2%) 2 (4%)
Hepatocyte, Vacuolization Cytoplasmic, Focal 9 (18%) 10 (20%) 11 (22%) 9 (18%)
Hepatocyte, Periportal, Vacuolization
Cytoplasmic 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Hepatocyte, Centrilobular, Necrosis 1 (2%) 1 (2%)
Hepatocyte, Centrilobular, Vacuolization
Cytoplasmic 1 (2%) 4 (8%) 1 (2%)
Mesentery (8) (10) (12) (9)
Fibrosis 1 (10%)
Hemorrhage, Focal 1 (11%)
Infiltration Cellular, Mixed Cell 1 (8%)
Inflammation, Chronic 1 (10%)
Artery, Inflammation, Chronic, Focal 1 (11%)
Fat, Necrosis 1 (10%) 2 (17%)
Fat, Necrosis, Focal 5 (63%) 7 (70%) 6 (50%) 3 (33%)
Pancreas (50) (49) (49) (50)
Infiltration Cellular, Diffuse, Mixed Cell 1 (2%)
Acinus, Atrophy, Diffuse 1 (2%) 1 (2%) 1 (2%)
Acinus, Atrophy, Focal 13 (26%) 14 (29%) 13 (27%) 11 (22%)
Duct, Cyst, Focal 1 (2%) 1 (2%)
Duct, Cyst, Focal, Multiple 9 (18%) 12 (24%) 4 (8%) 5 (10%)
Salivary Glands (50) (49) (50) (50)
Duct, Mineralization, Focal 2 (4%)
Stomach, Forestomach (50) (50) (50) (50)
Diverticulum 1 (2%) 1 (2%) 2 (4%)
Edema 1 (2%)
Erosion 1 (2%)
Inflammation, Chronic 1 (2%) 1 (2%)
Inflammation, Focal 1 (2%)
Ulcer 2 (4%) 1 (2%) 1 (2%)
Epithelium, Hyperplasia 3 (6%) 1 (2%) 4 (8%) 1 (2%)
Stomach, Glandular (49) (49) (48) (50)
Erosion 1 (2%) 1 (2%)
Inflammation, Chronic 1 (2%)
Necrosis, Focal 1 (2%)
Ulcer 1 (2%)
Epithelium, Hyperplasia, Focal 1 (2%)
Glands, Degeneration, Cystic, Focal 1 (2%)
Glands, Ectasia, Focal 1 (2%)
Glands, Hyperplasia, Focal 2 (4%)
Tongue (3) (1)
Epithelium, Hyperplasia, Focal 1 (33%)
Tooth (1)
Peridontal Tissue, Inflammation, Chronic 1 (100%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (49) (50) (50)
Cardiomyopathy 5 (10%) 8 (16%) 7 (14%) 6 (12%)
Infiltration Cellular, Mixed Cell 4 (8%) 3 (6%) 2 (4%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (49) (50) (50)
Accessory Adrenal Cortical Nodule 2 (4%) 2 (4%) 5 (10%) 5 (10%)
Angiectasis 1 (2%) 1 (2%) 1 (2%) 2 (4%)
Cytoplasmic Alteration, Focal 3 (6%) 1 (2%) 5 (10%)
Hematopoietic Cell Proliferation 1 (2%)
Hemorrhage 1 (2%)
Hemorrhage, Focal 1 (2%)
Vacuolization Cytoplasmic, Focal 8 (16%) 3 (6%) 7 (14%) 12 (24%)
Adrenal Medulla (49) (49) (50) (50)
Hyperplasia, Focal 1 (2%) 1 (2%) 1 (2%) 2 (4%)
Pituitary Gland (50) (48) (50) (50)
Angiectasis 5 (10%) 9 (19%) 7 (14%) 2 (4%)
Cyst 1 (2%)
Hemorrhage 1 (2%)
Metaplasia, Focal, Lipocyte 1 (2%)
Pars Distalis, Angiectasis 1 (2%)
Pars Distalis, Cyst 1 (2%) 3 (6%) 2 (4%) 1 (2%)
Pars Distalis, Cyst, Multiple 2 (4%)
Pars Distalis, Cytoplasmic Alteration, Focal 4 (8%) 4 (8%) 1 (2%) 3 (6%)
Pars Distalis, Degeneration, Cystic 1 (2%)
Pars Distalis, Degeneration, Cystic, Focal 9 (18%) 14 (29%) 8 (16%) 5 (10%)
Pars Distalis, Hemorrhage, Focal 1 (2%) 3 (6%) 4 (8%) 6 (12%)
Pars Distalis, Hyperplasia, Focal 1 (2%) 1 (2%) 1 (2%) 1 (2%)
Pars Distalis, Pigmentation, Focal 1 (2%)
Pars Intermedia, Cyst 1 (2%) 3 (6%)
Pars Intermedia, Degeneration, Cystic, Focal 1 (2%)
Pars Intermedia, Hemorrhage 1 (2%)
Pars Intermedia, Pars Nervosa, Atypia
Cellular, Focal 1 (2%)
Rathke's Cleft, Cyst 1 (2%) 1 (2%)
Rathke's Cleft, Hemorrhage 2 (4%)
Thyroid Gland (49) (48) (42) (48)
Vacuolization Cytoplasmic, Focal 1 (2%)
C-Cell, Hyperplasia 48 (98%) 46 (96%) 40 (95%) 25 (52%)
Follicle, Cyst 2 (4%) 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Follicle, Mineralization, Focal 42 (86%) 47 (98%) 41 (98%) 48 (100%)
Follicular Cell, Hyperplasia 41 (85%) 34 (81%) 46 (96%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (3) (4) (2)
Mediastinum, Infiltration Cellular, Mixed
Cell 1 (25%)
Pelvic, Hemorrhage, Focal 1 (50%)
Thoracic, Infiltration Cellular, Focal,
Mixed Cell 1 (25%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (50) (49) (50) (50)
Degeneration, Cystic 6 (12%) 4 (8%) 1 (2%) 1 (2%)
Fibrosis, Focal 1 (2%)
Hyperplasia, Cystic 1 (2%) 4 (8%) 3 (6%) 1 (2%)
Inflammation, Chronic 2 (4%) 5 (10%) 4 (8%)
Ovary (50) (49) (50) (50)
Angiectasis 1 (2%) 1 (2%)
Atrophy 1 (2%)
Congestion 1 (2%)
Cyst 5 (10%) 5 (10%) 1 (2%)
Bilateral, Cyst, Multiple 1 (2%)
Periovarian Tissue, Cyst 4 (8%) 5 (10%) 4 (8%) 6 (12%)
Periovarian Tissue, Cyst, Multiple 1 (2%)
Uterus (50) (50) (50) (50)
Cyst 3 (6%) 1 (2%) 1 (2%)
Hemorrhage 2 (4%)
Inflammation, Chronic 1 (2%)
Cervix, Hyperplasia 1 (2%)
Endometrium, Hyperplasia, Cystic 10 (20%) 14 (28%) 15 (30%) 15 (30%)
Vagina (2) (2)
Inflammation, Chronic 1 (50%)
Epithelium, Cyst 1 (50%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (49) (50) (50) (50)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Atrophy 1 (2%)
Fibrosis 1 (2%)
Hyperplasia, Focal, Histiocytic 1 (2%) 4 (8%)
Myelofibrosis 1 (2%)
Necrosis 1 (2%)
Myeloid Cell, Hyperplasia 2 (4%) 3 (6%) 5 (10%) 2 (4%)
Myeloid Cell, Erythroid Cell, Hyperplasia 2 (4%) 1 (2%)
Lymph Node (32) (31) (34) (41)
Deep Cervical, Hemorrhage 2 (5%)
Mediastinal, Angiectasis 1 (3%)
Mediastinal, Congestion 1 (3%)
Mediastinal, Ectasia 5 (16%) 3 (10%) 2 (6%) 7 (17%)
Mediastinal, Hemorrhage 2 (6%) 3 (10%) 9 (26%) 8 (20%)
Mediastinal, Hyperplasia 1 (3%) 2 (6%)
Mediastinal, Hyperplasia, Histiocytic 8 (25%) 8 (26%) 5 (15%) 12 (29%)
Mediastinal, Hyperplasia, Lymphoid 1 (3%) 1 (3%) 1 (2%)
Mediastinal, Pigmentation 1 (3%) 2 (6%)
Pancreatic, Atrophy 1 (3%)
Pancreatic, Ectasia 2 (6%) 2 (6%) 11 (27%)
Pancreatic, Hemorrhage 5 (16%) 3 (10%) 2 (6%) 9 (22%)
Pancreatic, Hyperplasia, Histiocytic 16 (50%) 24 (77%) 17 (50%) 18 (44%)
Pancreatic, Hyperplasia, Plasma Cell 1 (3%)
Pancreatic, Infiltration Cellular, Mixed Cell 1 (2%)
Pancreatic, Pigmentation 4 (13%) 2 (6%) 1 (2%)
Lymph Node, Mandibular (5) (4) (5) (1)
Ectasia 1 (20%)
Lymph Node, Mesenteric (49) (49) (49) (50)
Angiectasis 1 (2%)
Ectasia 1 (2%) 5 (10%)
Hemorrhage 1 (2%) 2 (4%) 2 (4%)
Hyperplasia, Histiocytic 2 (4%) 1 (2%) 2 (4%) 2 (4%)
Hyperplasia, Lymphoid 1 (2%)
Pigmentation 2 (4%)
Spleen (50) (49) (48) (50)
Accessory Spleen 1 (2%) 1 (2%)
Angiectasis, Focal 1 (2%)
Congestion 1 (2%)
Fibrosis, Focal 1 (2%) 1 (2%)
Hematopoietic Cell Proliferation 6 (12%) 8 (16%) 5 (10%) 4 (8%)
Hemorrhage 1 (2%)
Infarct 1 (2%)
Inflammation, Granulomatous 3 (6%) 2 (4%) 4 (8%) 27 (54%)
Pigmentation 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Pigmentation, Focal 1 (2%) 1 (2%) 1 (2%)
Thymus (48) (45) (49) (49)
Angiectasis 2 (4%)
Hyperplasia, Lymphoid 1 (2%) 1 (2%) 2 (4%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (50) (50) (50)
Dilatation 33 (66%) 35 (70%) 22 (44%) 19 (38%)
Ectasia 2 (4%) 3 (6%) 7 (14%)
Fibrosis 1 (2%)
Hyperplasia 3 (6%) 5 (10%) 4 (8%) 3 (6%)
Hyperplasia, Cystic 1 (2%) 2 (4%)
Inflammation, Focal 1 (2%)
Skin (50) (50) (50) (50)
Necrosis, Focal 4 (8%)
Ulcer 1 (2%) 1 (2%)
Subcutaneous Tissue, Angiectasis, Focal 1 (2%)
Subcutaneous Tissue, Hemorrhage, Focal 1 (2%)
Subcutaneous Tissue, Inflammation, Focal,
Suppurative 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (49) (50) (50)
Compression, Focal 10 (20%) 8 (16%) 12 (24%) 4 (8%)
Hemorrhage, Focal 2 (4%) 1 (2%) 2 (4%)
Necrosis, Focal 2 (4%)
Pigmentation, Focal 1 (2%)
Cerebellum, Developmental Malformation 1 (2%)
Spinal Cord (3) (1) (4)
Hemorrhage, Focal 1 (33%)
Necrosis, Focal 1 (33%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (49) (50) (50)
Congestion 2 (4%) 4 (8%) 2 (4%) 2 (4%)
Emphysema 1 (2%)
Hemorrhage 1 (2%)
Hemorrhage, Focal 1 (2%) 2 (4%)
Hyperplasia, Focal, Histiocytic 1 (2%) 1 (2%)
Hyperplasia, Histiocytic 6 (12%) 6 (12%) 7 (14%) 1 (2%)
Infiltration Cellular, Focal, Mixed Cell 1 (2%)
Infiltration Cellular, Mixed Cell 3 (6%) 1 (2%) 6 (12%)
Inflammation, Chronic, Focal 1 (2%) 2 (4%) 1 (2%)
Inflammation, Focal, Granulomatous 1 (2%) 1 (2%)
Pigmentation, Focal 1 (2%)
Alveolar Epithelium, Hyperplasia, Focal 7 (14%) 5 (10%) 3 (6%) 3 (6%)
Alveolus, Inflammation, Focal, Granulomatous 1 (2%)
Interstitium, Edema 1 (2%)
Nose (50) (49) (50) (50)
Foreign Body 1 (2%) 1 (2%)
Inflammation, Suppurative 1 (2%) 1 (2%) 2 (4%)
Nasolacrimal Duct, Inflammation 4 (8%) 2 (4%) 4 (8%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (50) (49) (49) (50)
Atrophy 1 (2%) 1 (2%) 1 (2%)
Cataract 1 (2%) 2 (4%) 2 (4%) 1 (2%)
Iris, Synechia 1 (2%)
Retina, Degeneration 2 (4%) 1 (2%) 1 (2%)
Harderian Gland (50) (49) (50) (50)
Hyperplasia, Cystic, Focal 1 (2%)
Hyperplasia, Focal 2 (4%) 1 (2%) 1 (2%)
Hyperplasia, Focal, Histiocytic 1 (2%) 2 (4%) 1 (2%) 4 (8%)
Inflammation, Chronic, Focal 3 (6%) 1 (2%)
Inflammation, Focal, Granulomatous 1 (2%)
Epithelium, Hyperplasia, Focal 2 (4%) 2 (4%) 1 (2%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (48) (47) (50)
Atrophy, Focal 2 (4%) 1 (2%)
Congestion 2 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0PPM 1000 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Cyst 1 (2%)
Infarct 1 (2%)
Nephropathy 38 (76%) 40 (83%) 38 (81%) 40 (80%)
Glomerulus, Amyloid Deposition, Diffuse 1 (2%)
Pelvis, Inflammation 1 (2%)
Renal Tubule, Accumulation, Hyaline Droplet 11 (22%) 7 (15%) 3 (6%) 4 (8%)
Renal Tubule, Pigmentation 8 (16%) 4 (8%) 5 (11%)
Urethra (2)
Transitional Epithelium, Hyperplasia, Diffuse 1 (50%)
Urinary Bladder (50) (49) (49) (50)
Transitional Epithelium, Hyperplasia 2 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 9
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 60 60 60 60
Early Deaths
Moribund Sacrifice 13 6 7 13
Natural Death 2 4 7 2
Survivors
Terminal Sacrifice 34 39 35 35
Moribund Sacrifice 1
Natural Death 1 1
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Rectum (49) (48) (48) (50)
Angiectasis, Focal 1 (2%)
Liver (50) (50) (50) (50)
Angiectasis, Focal 1 (2%)
Basophilic Focus 23 (46%) 23 (46%) 8 (16%) 2 (4%)
Cholangiofibrosis 1 (2%) 1 (2%)
Congestion 2 (4%) 1 (2%)
Degeneration, Cystic, Focal 4 (8%) 3 (6%) 2 (4%) 7 (14%)
Eosinophilic Focus 3 (6%) 6 (12%) 1 (2%)
Fibrosis, Focal 1 (2%)
Hematopoietic Cell Proliferation 2 (4%)
Hepatodiaphragmatic Nodule 6 (12%) 5 (10%) 4 (8%) 9 (18%)
Hyperplasia, Focal, Lymphoid 1 (2%) 2 (4%) 1 (2%)
Infiltration Cellular, Mixed Cell 25 (50%) 30 (60%) 27 (54%) 36 (72%)
Inflammation, Granulomatous 12 (24%) 11 (22%) 4 (8%) 11 (22%)
Mixed Cell Focus 14 (28%) 16 (32%) 23 (46%) 26 (52%)
Necrosis, Focal 2 (4%) 2 (4%) 1 (2%)
Pigmentation, Focal 2 (4%)
Bile Duct, Cyst 1 (2%)
Bile Duct, Hyperplasia 49 (98%) 49 (98%) 47 (94%) 49 (98%)
Centrilobular, Congestion 1 (2%)
Hepatocyte, Necrosis, Focal 1 (2%) 1 (2%) 3 (6%) 2 (4%)
Hepatocyte, Vacuolization Cytoplasmic,
Diffuse 1 (2%) 1 (2%)
Hepatocyte, Vacuolization Cytoplasmic, Focal 23 (46%) 30 (60%) 26 (52%) 23 (46%)
Hepatocyte, Centrilobular, Necrosis 2 (4%) 2 (4%)
Hepatocyte, Centrilobular, Vacuolization
Cytoplasmic 5 (10%) 4 (8%) 3 (6%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 10
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Hepatocyte, Midzonal, Vacuolization
Cytoplasmic 1 (2%) 1 (2%) 2 (4%)
Oval Cell, Hyperplasia 1 (2%)
Serosa, Fibrosis, Focal 2 (4%)
Mesentery (26) (46) (35) (20)
Fibrosis, Focal 1 (5%)
Hemorrhage 2 (10%)
Necrosis, Focal 1 (5%)
Artery, Inflammation, Chronic 1 (5%)
Fat, Necrosis 1 (4%) 1 (2%) 2 (6%)
Fat, Necrosis, Focal 8 (31%) 10 (22%) 16 (46%) 10 (50%)
Pancreas (49) (49) (50) (50)
Atrophy, Diffuse 1 (2%)
Atrophy, Focal 1 (2%) 1 (2%)
Fibrosis, Focal 1 (2%)
Acinus, Atrophy, Diffuse 1 (2%) 1 (2%)
Acinus, Atrophy, Focal 22 (45%) 27 (55%) 20 (40%) 36 (72%)
Acinus, Hyperplasia, Focal 1 (2%)
Duct, Cyst 1 (2%)
Duct, Cyst, Focal 1 (2%)
Duct, Cyst, Focal, Multiple 6 (12%) 2 (4%) 5 (10%) 12 (24%)
Duct, Hyperplasia, Cystic 1 (2%) 1 (2%)
Duct, Hyperplasia, Cystic, Focal 2 (4%) 3 (6%)
Duct, Hyperplasia, Focal 1 (2%)
Salivary Glands (50) (50) (50) (50)
Atrophy, Focal 1 (2%)
Inflammation, Chronic 1 (2%)
Stomach, Forestomach (50) (50) (50) (49)
Diverticulum 1 (2%) 1 (2%) 2 (4%) 1 (2%)
Edema 1 (2%)
Erosion 1 (2%) 1 (2%)
Inflammation, Focal 1 (2%) 1 (2%)
Ulcer 2 (4%) 1 (2%) 1 (2%) 4 (8%)
Epithelium, Hyperplasia 2 (4%) 3 (6%) 6 (12%)
Epithelium, Hyperplasia, Focal 1 (2%)
Serosa, Foreign Body 1 (2%)
Serosa, Inflammation, Chronic, Focal 1 (2%)
Stomach, Glandular (50) (50) (50) (49)
Erosion 4 (8%) 1 (2%) 1 (2%)
Erosion, Focal 1 (2%) 1 (2%)
Inflammation, Focal 1 (2%)
Ulcer 2 (4%)
Epithelium, Necrosis, Focal 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 11
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Glands, Hyperplasia, Cystic, Focal 1 (2%)
Glands, Hyperplasia, Focal 1 (2%)
Tongue (1) (2) (1)
Epithelium, Hyperplasia, Focal 1 (100%)
Tooth (1) (1) (1) (2)
Malformation 1 (100%)
Peridontal Tissue, Inflammation 1 (100%)
Peridontal Tissue, Inflammation, Chronic 1 (50%)
Peridontal Tissue, Inflammation, Focal,
Suppurative 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Cardiomyopathy 3 (6%) 5 (10%) 10 (20%) 5 (10%)
Cardiomyopathy, Focal 2 (4%) 1 (2%)
Congestion 1 (2%)
Fibrosis 1 (2%)
Infiltration Cellular, Mixed Cell 1 (2%)
Thrombosis 1 (2%) 1 (2%)
Endocardium, Myocardium, Fibrosis, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50)
Accessory Adrenal Cortical Nodule 1 (2%) 4 (8%) 9 (18%) 5 (10%)
Cytoplasmic Alteration, Focal 2 (4%) 1 (2%) 1 (2%) 3 (6%)
Degeneration, Cystic, Focal 1 (2%)
Hemorrhage 2 (4%)
Vacuolization Cytoplasmic, Focal 6 (12%) 9 (18%) 10 (20%) 10 (20%)
Adrenal Medulla (50) (50) (50) (50)
Angiectasis 1 (2%)
Hyperplasia 1 (2%) 1 (2%) 1 (2%)
Hyperplasia, Focal 7 (14%) 5 (10%) 3 (6%) 7 (14%)
Infiltration Cellular, Lymphoid 1 (2%)
Vacuolization Cytoplasmic, Focal 1 (2%)
Islets, Pancreatic (50) (49) (50) (50)
Atrophy 1 (2%)
Hyperplasia, Focal 2 (4%) 1 (2%) 1 (2%)
Parathyroid Gland (47) (49) (48) (49)
Cyst 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 12
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Hyperplasia 1 (2%)
Hyperplasia, Focal 1 (2%) 1 (2%)
Bilateral, Hyperplasia, Focal 1 (2%)
Pituitary Gland (50) (50) (50) (50)
Angiectasis 2 (4%) 3 (6%)
Pars Distalis, Angiectasis 3 (6%) 2 (4%) 2 (4%) 1 (2%)
Pars Distalis, Cyst 1 (2%) 4 (8%) 2 (4%) 3 (6%)
Pars Distalis, Cytoplasmic Alteration, Focal 1 (2%) 4 (8%) 2 (4%) 5 (10%)
Pars Distalis, Degeneration, Cystic, Focal 1 (2%) 1 (2%) 1 (2%) 1 (2%)
Pars Distalis, Hyperplasia, Focal 2 (4%) 1 (2%) 2 (4%)
Pars Distalis, Inflammation, Chronic, Focal,
Granulomatous 1 (2%)
Pars Distalis, Pars Intermedia, Angiectasis 1 (2%)
Pars Intermedia, Cyst 2 (4%) 1 (2%)
Pars Intermedia, Hemorrhage 1 (2%)
Pars Intermedia, Hyperplasia, Focal 1 (2%)
Pars Nervosa, Infiltration Cellular, Focal,
Mixed Cell 1 (2%)
Thyroid Gland (48) (46) (43) (50)
Cyst 1 (2%)
C-Cell, Hyperplasia 41 (85%) 43 (93%) 38 (88%) 34 (68%)
Follicle, Cyst 1 (2%) 1 (2%)
Follicle, Mineralization, Focal 48 (100%) 45 (98%) 43 (100%) 49 (98%)
Follicular Cell, Atrophy, Focal 1 (2%)
Follicular Cell, Hyperplasia 17 (37%) 37 (86%) 43 (86%)
Follicular Cell, Hyperplasia, Cystic, Focal 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (7) (2) (6) (4)
Mediastinum, Hemorrhage 1 (25%)
Thoracic, Hemorrhage 1 (25%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (50) (50) (50) (50)
Atrophy 1 (2%) 1 (2%)
Granuloma Sperm 1 (2%) 1 (2%) 1 (2%)
Inflammation, Chronic 1 (2%) 1 (2%)
Preputial Gland (50) (50) (50) (50)
Cyst 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 13
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT
Degeneration, Cystic 2 (4%)
Hyperplasia 1 (2%)
Hyperplasia, Cystic 2 (4%) 2 (4%) 1 (2%)
Hyperplasia, Focal 1 (2%)
Inflammation, Chronic 4 (8%) 10 (20%) 10 (20%) 11 (22%)
Inflammation, Chronic, Focal 1 (2%)
Inflammation, Suppurative 1 (2%) 1 (2%) 2 (4%)
Prostate (50) (50) (50) (50)
Atrophy 1 (2%)
Hyperplasia, Focal 1 (2%)
Inflammation, Chronic 15 (30%) 10 (20%) 17 (34%) 19 (38%)
Epithelium, Degeneration, Focal, Mucoid 1 (2%)
Epithelium, Hyperplasia, Focal 4 (8%) 2 (4%) 5 (10%)
Testes (50) (50) (50) (50)
Atrophy 5 (10%) 4 (8%) 13 (26%) 13 (26%)
Mineralization, Focal 1 (2%)
Bilateral, Atrophy 2 (4%) 3 (6%) 2 (4%)
Bilateral, Interstitial Cell, Hyperplasia,
Focal 2 (4%)
Germinal Epithelium, Atrophy 2 (4%) 3 (6%) 1 (2%) 1 (2%)
Interstitial Cell, Hyperplasia 2 (4%) 1 (2%) 1 (2%)
Interstitial Cell, Hyperplasia, Focal 1 (2%) 4 (8%) 4 (8%) 9 (18%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (47) (50)
Fibrosis 1 (2%)
Hyperplasia 1 (2%)
Hyperplasia, Focal, Histiocytic 1 (2%) 1 (2%)
Myeloid Cell, Hyperplasia 1 (2%) 5 (10%)
Lymph Node (39) (49) (42) (38)
Hemorrhage 1 (3%)
Hyperplasia, Lymphoid 1 (2%)
Mediastinal, Angiectasis 1 (2%)
Mediastinal, Congestion 1 (2%)
Mediastinal, Ectasia 1 (3%) 3 (7%) 1 (3%)
Mediastinal, Hemorrhage 1 (3%) 1 (2%) 5 (12%) 1 (3%)
Mediastinal, Hyperplasia, Histiocytic 2 (5%) 1 (2%) 4 (11%)
Mediastinal, Hyperplasia, Lymphoid 1 (3%) 1 (2%) 1 (2%) 1 (3%)
Mediastinal, Pigmentation 1 (2%) 1 (3%)
Pancreatic, Angiectasis 1 (3%) 1 (3%)
Pancreatic, Ectasia 1 (3%) 3 (6%) 3 (7%) 2 (5%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 14
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Pancreatic, Hemorrhage 1 (3%) 1 (2%) 4 (11%)
Pancreatic, Hyperplasia, Focal, Histiocytic 1 (3%)
Pancreatic, Hyperplasia, Histiocytic 13 (33%) 12 (24%) 15 (36%) 19 (50%)
Pancreatic, Hyperplasia, Lymphoid 1 (2%) 1 (3%)
Pancreatic, Pigmentation 1 (3%) 1 (3%)
Lymph Node, Mandibular (2) (1) (2) (2)
Hyperplasia, Plasma Cell 1 (50%)
Lymph Node, Mesenteric (47) (50) (50) (50)
Ectasia 2 (4%) 2 (4%)
Hemorrhage 1 (2%) 1 (2%)
Hyperplasia, Histiocytic 1 (2%) 2 (4%) 1 (2%) 4 (8%)
Hyperplasia, Lymphoid 2 (4%) 1 (2%)
Spleen (49) (49) (50) (50)
Angiectasis, Focal 1 (2%) 1 (2%)
Congestion 1 (2%)
Cyst 1 (2%)
Fibrosis, Focal 2 (4%) 2 (4%) 1 (2%)
Hematopoietic Cell Proliferation 4 (8%) 4 (8%) 1 (2%) 6 (12%)
Hemorrhage 1 (2%)
Hemorrhage, Focal 1 (2%)
Hyperplasia, Lymphoid 1 (2%) 2 (4%)
Infarct 1 (2%) 1 (2%)
Inflammation, Granulomatous 2 (4%) 3 (6%)
Necrosis, Focal 1 (2%) 1 (2%) 1 (2%)
Pigmentation 1 (2%)
Capsule, Fibrosis, Focal 1 (2%)
Thymus (48) (48) (44) (49)
Atrophy 1 (2%) 1 (2%)
Cyst, Multiple 1 (2%)
Hemorrhage 1 (2%) 1 (2%)
Hyperplasia, Lymphoid 2 (4%) 1 (2%) 1 (2%)
Epithelial Cell, Cyst, Multiple 1 (2%)
Epithelial Cell, Hyperplasia 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (48) (47) (45) (42)
Dilatation 7 (15%) 1 (2%) 3 (7%) 2 (5%)
Ectasia 1 (2%)
Hyperplasia 2 (4%)
Hyperplasia, Cystic 1 (2%)
Epithelium, Pigmentation 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 15
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM - CONT
Skin (50) (50) (50) (50)
Angiectasis, Focal 1 (2%)
Cyst Epithelial Inclusion 1 (2%) 1 (2%)
Fibrosis, Focal 1 (2%)
Hemorrhage, Focal 1 (2%) 1 (2%)
Inflammation, Chronic, Focal 1 (2%) 1 (2%) 1 (2%)
Necrosis, Focal 1 (2%)
Pinna, Necrosis, Focal 1 (2%)
Subcutaneous Tissue, Angiectasis, Focal 1 (2%)
Subcutaneous Tissue, Cyst 1 (2%)
Subcutaneous Tissue, Foreign Body 1 (2%)
Subcutaneous Tissue, Hemorrhage, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Skeletal Muscle (2) (1) (1) (4)
Fibrosis, Focal 1 (25%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Compression, Focal 4 (8%) 2 (4%) 4 (8%) 1 (2%)
Hemorrhage, Focal 2 (4%) 3 (6%) 2 (4%) 1 (2%)
Necrosis, Focal 1 (2%) 1 (2%)
Spinal Cord (1) (1)
Hemorrhage, Focal 1 (100%)
Mineralization, Focal 1 (100%)
Necrosis, Focal 1 (100%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Larynx (1) (1)
Glands, Hyperplasia, Focal 1 (100%)
Lung (50) (50) (50) (50)
Congestion 1 (2%) 1 (2%) 1 (2%)
Hemorrhage, Focal 1 (2%) 1 (2%) 1 (2%)
Hyperplasia, Focal, Histiocytic 4 (8%) 1 (2%)
Hyperplasia, Histiocytic 3 (6%) 3 (6%) 2 (4%) 2 (4%)
Infiltration Cellular, Focal, Mixed Cell 1 (2%)
Infiltration Cellular, Mixed Cell 2 (4%) 1 (2%) 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 16
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Inflammation, Focal 1 (2%)
Metaplasia, Focal, Osseous 2 (4%) 1 (2%) 2 (4%)
Metaplasia, Osseous 2 (4%)
Alveolar Epithelium, Hyperplasia, Focal 2 (4%) 9 (18%) 6 (12%) 5 (10%)
Alveolus, Foreign Body, Focal 1 (2%)
Interstitium, Edema 1 (2%) 1 (2%)
Nose (50) (50) (50) (50)
Foreign Body 1 (2%)
Inflammation, Suppurative 2 (4%) 1 (2%)
Nasolacrimal Duct, Inflammation 2 (4%) 1 (2%) 2 (4%)
Nasolacrimal Duct, Inflammation, Chronic 1 (2%)
Nasolacrimal Duct, Inflammation, Suppurative 3 (6%)
Sinus, Foreign Body 1 (2%)
Sinus, Inflammation, Suppurative 1 (2%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (49) (50) (46) (50)
Atrophy 1 (2%)
Cataract 1 (2%) 1 (2%)
Synechia 1 (2%)
Cornea, Inflammation, Focal 1 (2%)
Cornea, Necrosis, Focal 1 (2%)
Iris, Hyperplasia 1 (2%)
Lens, Cataract 1 (2%)
Retina, Degeneration 1 (2%)
Retrobulbar, Inflammation, Focal 1 (2%)
Harderian Gland (50) (50) (49) (50)
Hyperplasia, Focal 1 (2%) 2 (4%)
Hyperplasia, Focal, Histiocytic 1 (2%)
Hyperplasia, Histiocytic 1 (2%)
Inflammation, Chronic, Focal 1 (2%) 2 (4%) 3 (6%)
Inflammation, Focal, Granulomatous 1 (2%)
Epithelium, Hyperplasia, Focal 3 (6%) 1 (2%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (49) (49) (49) (50)
Accumulation, Hyaline Droplet 1 (2%)
Atrophy, Focal 1 (2%)
Congestion 1 (2%) 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 17
NTP Experiment-Test: 92012-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 2-METHYLIMIDAZOLE Date: 03/14/03
Route: DOSED FEED Time: 10:29:56
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0PPM 300 PPM 1000 PPM 3000 PPM
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Cyst 2 (4%) 2 (4%)
Fibrosis, Focal 1 (2%)
Infarct 1 (2%)
Inflammation 1 (2%)
Nephropathy 43 (88%) 43 (88%) 41 (84%) 46 (92%)
Pelvis, Inflammation, Chronic 1 (2%)
Pelvis, Transitional Epithelium, Hyperplasia 1 (2%)
Renal Tubule, Accumulation, Hyaline Droplet 1 (2%) 1 (2%) 3 (6%) 2 (4%)
Renal Tubule, Necrosis, Focal 1 (2%)
Renal Tubule, Pigmentation 5 (10%) 3 (6%) 2 (4%) 3 (6%)
Urinary Bladder (50) (50) (49) (50)
Hemorrhage 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 18
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