TDMS Study 92013-05 Pathology Tables
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
FINAL #1 RATS
Facility: Southern Research Institute
Chemical CAS #: 822-36-6
Lock Date: 09/13/02
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: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50
Early Deaths
Natural Death 2 6 11 6
Moribund Sacrifice 5 5 5 9
Survivors
Terminal Sacrifice 40 39 34 33
Natural Death 3 2
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (48) (46) (43) (43)
Edema 1 (2%)
Liver (50) (50) (48) (50)
Basophilic Focus 46 (92%) 43 (86%) 31 (65%) 25 (50%)
Clear Cell Focus 20 (40%) 32 (64%) 23 (48%) 27 (54%)
Congestion 2 (4%) 2 (4%) 1 (2%)
Degeneration, Cystic, Focal 1 (2%) 1 (2%) 3 (6%)
Eosinophilic Focus 1 (2%) 2 (4%) 5 (10%) 11 (22%)
Hematopoietic Cell Proliferation 1 (2%)
Hemorrhage 1 (2%)
Hepatodiaphragmatic Nodule 5 (10%) 4 (8%) 6 (13%) 11 (22%)
Histiocytosis 40 (80%) 50 (100%) 48 (100%) 50 (100%)
Hyperplasia, Focal, Histiocytic 2 (4%)
Infiltration Cellular, Mixed Cell 5 (10%) 5 (10%) 5 (10%)
Inflammation, Chronic 17 (34%) 28 (56%) 34 (71%) 35 (70%)
Inflammation, Chronic, Focal 1 (2%)
Inflammation, Granulomatous 1 (2%)
Mixed Cell Focus 10 (20%) 7 (14%) 6 (13%) 18 (36%)
Thrombosis 1 (2%)
Bile Duct, Cyst 1 (2%)
Bile Duct, Dilatation, Focal 2 (4%) 1 (2%)
Bile Duct, Hyperplasia 31 (62%) 38 (76%) 43 (90%) 35 (70%)
Hepatocyte, Fatty Change, Focal 16 (32%) 29 (58%) 29 (60%) 32 (64%)
Hepatocyte, Hyperplasia, Focal 1 (2%)
Hepatocyte, Necrosis, Focal 1 (2%) 1 (2%)
Hepatocyte, Vacuolization Cytoplasmic 6 (12%) 12 (24%) 17 (35%) 11 (22%)
Hepatocyte, Centrilobular, Necrosis 2 (4%) 1 (2%) 1 (2%)
Oval Cell, Hyperplasia, Focal 1 (2%) 2 (4%)
Serosa, Fibrosis 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Mesentery (9) (7) (11) (8)
Inflammation, Chronic 1 (11%) 1 (9%)
Fat, Necrosis, Focal 8 (89%) 3 (43%) 1 (13%)
Lymphatic, Angiectasis 1 (13%)
Pancreas (49) (49) (47) (47)
Acinus, Atrophy, Diffuse 1 (2%)
Acinus, Atrophy, Focal 13 (27%) 22 (45%) 26 (55%) 30 (64%)
Duct, Cyst, Focal, Multiple 10 (20%) 18 (37%) 11 (23%) 9 (19%)
Salivary Glands (50) (50) (50) (50)
Atrophy, Focal 2 (4%)
Inflammation, Chronic 1 (2%) 1 (2%) 1 (2%)
Stomach, Forestomach (50) (50) (49) (50)
Diverticulum 1 (2%)
Edema 1 (2%) 1 (2%) 2 (4%) 1 (2%)
Inflammation 2 (4%)
Ulcer 1 (2%) 1 (2%) 3 (6%) 2 (4%)
Epithelium, Hyperplasia 1 (2%) 6 (12%) 1 (2%)
Stomach, Glandular (50) (50) (49) (49)
Erosion 2 (4%) 1 (2%) 1 (2%) 4 (8%)
Ulcer 1 (2%)
Tongue (5) (4) (3)
Epithelium, Hyperplasia 1 (20%) 1 (25%)
Tooth (1) (1) (2)
Malformation 1 (100%) 2 (100%)
Peridontal Tissue, Inflammation 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (48) (50)
Cardiomyopathy 30 (60%) 43 (86%) 38 (79%) 44 (88%)
Inflammation, Focal, Suppurative 1 (2%)
Thrombosis 2 (4%) 5 (10%)
Artery, Inflammation, Chronic 1 (2%)
Epicardium, Inflammation 1 (2%)
Myocardium, Fibrosis, Focal 1 (2%)
Pericardium, Infiltration Cellular, Mixed
Cell 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (50) (50) (50)
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Accessory Adrenal Cortical Nodule 8 (16%) 6 (12%) 3 (6%) 2 (4%)
Angiectasis 4 (8%) 2 (4%) 7 (14%) 4 (8%)
Cytoplasmic Alteration, Focal 1 (2%) 2 (4%) 2 (4%) 2 (4%)
Hematopoietic Cell Proliferation 1 (2%)
Hemorrhage, Focal 2 (4%) 1 (2%)
Vacuolization Cytoplasmic, Focal 8 (16%) 9 (18%) 13 (26%) 12 (24%)
Adrenal Medulla (48) (50) (50) (50)
Angiectasis 1 (2%) 1 (2%)
Atrophy 1 (2%)
Hyperplasia, Focal 2 (4%) 2 (4%)
Hyperplasia, Lymphoid 1 (2%)
Islets, Pancreatic (49) (50) (48) (47)
Atrophy 1 (2%)
Parathyroid Gland (50) (49) (48) (49)
Hyperplasia, Focal 1 (2%)
Pituitary Gland (48) (50) (50) (50)
Angiectasis 6 (13%) 4 (8%) 3 (6%) 4 (8%)
Cyst 4 (8%) 2 (4%) 5 (10%)
Hyperplasia, Focal, Histiocytic 1 (2%)
Pars Distalis, Angiectasis 1 (2%) 2 (4%) 3 (6%)
Pars Distalis, Degeneration, Cystic, Focal 9 (19%) 6 (12%) 5 (10%) 3 (6%)
Pars Distalis, Hemorrhage, Focal 1 (2%)
Pars Distalis, Hyperplasia, Focal 4 (8%) 4 (8%) 5 (10%) 4 (8%)
Pars Distalis, Hypertrophy, Focal 1 (2%) 1 (2%) 4 (8%)
Thyroid Gland (47) (44) (40) (45)
C-Cell, Hyperplasia 45 (96%) 42 (95%) 36 (90%) 35 (78%)
Follicle, Cyst 1 (2%)
Follicle, Degeneration, Focal 1 (3%) 1 (2%)
Follicle, Mineralization 2 (4%) 7 (16%) 6 (15%) 19 (42%)
Follicular Cell, Hyperplasia, Focal 1 (2%) 1 (2%) 1 (3%) 2 (4%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (5) (3) (6) (6)
Fibrosis, Focal 1 (20%)
Mediastinum, Cyst 1 (20%)
Mediastinum, Infiltration Cellular, Mixed
Cell 1 (20%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT
Clitoral Gland (50) (50) (50) (50)
Degeneration, Cystic 4 (8%) 5 (10%) 3 (6%)
Hyperplasia, Cystic 7 (14%) 4 (8%) 1 (2%) 1 (2%)
Hyperplasia, Focal, Histiocytic 1 (2%)
Inflammation, Chronic 2 (4%) 2 (4%) 3 (6%)
Ovary (50) (50) (48) (50)
Angiectasis 2 (4%)
Cyst 7 (14%) 3 (6%) 5 (10%)
Periovarian Tissue, Hemorrhage 1 (2%)
Uterus (50) (50) (48) (50)
Inflammation, Chronic, Granulomatous 1 (2%)
Ulcer 1 (2%)
Cervix, Hypertrophy 1 (2%)
Endometrium, Hyperplasia, Cystic 25 (50%) 26 (52%) 18 (38%) 26 (52%)
Vagina (1) (2) (5) (4)
Angiectasis 1 (25%)
Infiltration Cellular, Polymorphonuclear 1 (50%) 1 (25%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (48) (49) (48)
Atrophy 2 (4%)
Fibrosis 1 (2%) 1 (2%)
Hyperplasia 3 (6%) 2 (4%) 1 (2%) 2 (4%)
Hyperplasia, Focal, Histiocytic 1 (2%) 2 (4%) 3 (6%)
Erythroid Cell, Hyperplasia 1 (2%)
Lymph Node (24) (11) (24) (35)
Hyperplasia, Plasma Cell 1 (3%)
Deep Cervical, Hemorrhage 3 (13%)
Mediastinal, Congestion 1 (9%)
Mediastinal, Ectasia 3 (13%) 1 (9%) 1 (3%)
Mediastinal, Hemorrhage 5 (21%) 3 (27%) 5 (21%) 3 (9%)
Mediastinal, Hyperplasia, Histiocytic 4 (17%) 1 (9%) 1 (4%) 6 (17%)
Mediastinal, Hyperplasia, Lymphoid 1 (4%) 1 (3%)
Mediastinal, Hyperplasia, Plasma Cell 1 (4%)
Mediastinal, Pigmentation 1 (4%)
Pancreatic, Hemorrhage 1 (4%) 2 (8%) 2 (6%)
Pancreatic, Hyperplasia, Histiocytic 6 (25%) 1 (9%) 7 (29%) 7 (20%)
Pancreatic, Hyperplasia, Lymphoid 1 (3%)
Pancreatic, Hyperplasia, Plasma Cell 1 (4%)
Pancreatic, Pigmentation 1 (4%)
Renal, Hyperplasia, Histiocytic 1 (3%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Lymph Node, Mandibular (1) (3) (1) (4)
Ectasia 1 (33%)
Hyperplasia, Histiocytic 1 (25%)
Hyperplasia, Lymphoid 1 (100%)
Lymph Node, Mesenteric (49) (49) (49) (47)
Ectasia 2 (4%)
Hemorrhage 1 (2%)
Hyperplasia, Histiocytic 7 (14%) 1 (2%) 2 (4%)
Hyperplasia, Lymphoid 1 (2%)
Spleen (50) (48) (47) (48)
Accessory Spleen 3 (6%) 1 (2%) 1 (2%)
Atrophy 2 (4%)
Congestion 1 (2%)
Fibrosis, Focal 1 (2%) 1 (2%) 1 (2%)
Hematopoietic Cell Proliferation 6 (12%) 2 (4%)
Inflammation, Granulomatous 3 (6%) 10 (21%) 3 (6%)
Stromal Hyperplasia 1 (2%)
Capsule, Infiltration Cellular, Focal, Mixed
Cell 2 (4%) 1 (2%)
Thymus (47) (50) (48) (48)
Angiectasis 1 (2%)
Cyst 2 (4%)
Hemorrhage 1 (2%)
Hyperplasia, Lymphoid 1 (2%) 1 (2%) 1 (2%)
Epithelial Cell, Hyperplasia 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (49) (50) (50)
Dilatation 37 (74%) 16 (33%) 8 (16%) 1 (2%)
Fibrosis 1 (2%)
Hyperplasia 6 (12%) 3 (6%) 3 (6%) 1 (2%)
Skin (50) (50) (50) (50)
Inflammation, Focal 1 (2%)
Ulcer 1 (2%) 1 (2%) 1 (2%)
Epidermis, Hyperplasia, Focal 1 (2%) 2 (4%)
Lip, Cyst Epithelial Inclusion 1 (2%)
Pinna, Inflammation, Chronic, Focal 1 (2%)
Subcutaneous Tissue, Edema 1 (2%) 1 (2%) 1 (2%)
Subcutaneous Tissue, Fibrosis, Focal 1 (2%)
Subcutaneous Tissue, Hemorrhage, Focal 1 (2%)
Subcutaneous Tissue, Necrosis, Fatty, Focal 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Compression, Focal 13 (26%) 8 (16%) 8 (16%) 2 (4%)
Hemorrhage, Focal 1 (2%) 2 (4%) 4 (8%) 2 (4%)
Meninges, Hemorrhage, Focal 1 (2%)
Thalamus, Mineralization, Focal 1 (2%) 1 (2%)
Spinal Cord (7) (3) (24) (50)
Hemorrhage, Focal 2 (4%)
Necrosis, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Congestion 1 (2%) 5 (10%) 3 (6%) 5 (10%)
Hemorrhage, Focal 1 (2%) 2 (4%) 2 (4%)
Hyperplasia, Focal, Histiocytic 1 (2%) 2 (4%)
Infiltration Cellular, Mixed Cell 3 (6%) 1 (2%) 1 (2%)
Inflammation, Chronic, Focal 25 (50%) 40 (80%) 39 (78%) 43 (86%)
Alveolar Epithelium, Hyperplasia, Focal 4 (8%) 3 (6%) 2 (4%)
Interstitium, Edema 1 (2%) 1 (2%)
Mediastinum, Congestion 1 (2%)
Mediastinum, Edema 1 (2%) 1 (2%) 1 (2%)
Mediastinum, Mineralization, Focal 1 (2%)
Nose (49) (50) (50) (50)
Foreign Body 2 (4%)
Inflammation, Suppurative 3 (6%) 1 (2%)
Nasolacrimal Duct, Hemorrhage 1 (2%)
Nasolacrimal Duct, Inflammation 2 (4%) 5 (10%) 4 (8%) 5 (10%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (48) (45) (40) (45)
Atrophy 3 (8%) 4 (9%)
Cataract 4 (8%) 1 (3%) 1 (2%)
Inflammation, Chronic 1 (2%) 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Synechia 1 (2%) 2 (4%)
Anterior Chamber, Exudate 1 (2%) 1 (2%)
Cornea, Inflammation, Chronic 1 (2%)
Cornea, Necrosis, Focal 1 (2%) 1 (3%) 2 (4%)
Retina, Degeneration 4 (8%) 1 (2%) 3 (7%)
Harderian Gland (50) (50) (50) (50)
Cytoplasmic Alteration, Focal 1 (2%)
Hyperplasia, Focal, Histiocytic 1 (2%) 4 (8%) 5 (10%)
Inflammation 1 (2%) 1 (2%)
Epithelium, Hyperplasia, Focal 1 (2%)
Zymbal's Gland (3) (1)
Cyst 1 (33%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (48) (48) (43) (43)
Cyst 2 (5%)
Hydronephrosis 1 (2%)
Infarct 1 (2%) 1 (2%) 1 (2%) 2 (5%)
Mineralization, Focal 1 (2%)
Nephropathy 45 (94%) 37 (77%) 36 (84%) 38 (88%)
Pelvis, Dilatation 1 (2%)
Renal Tubule, Accumulation, Hyaline Droplet 3 (6%) 2 (5%) 1 (2%)
Renal Tubule, Hyperplasia, Focal 1 (2%)
Renal Tubule, Pigmentation 2 (5%)
Urinary Bladder (49) (50) (49) (48)
Hemorrhage 1 (2%) 2 (4%)
Inflammation 1 (2%) 1 (2%)
Transitional Epithelium, Hyperplasia 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50
Early Deaths
Moribund Sacrifice 13 11 12 10
Natural Death 6 5 5 8
Survivors
Terminal Sacrifice 31 34 33 32
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (46) (46) (46) (46)
Congestion 1 (2%)
Edema 1 (2%)
Liver (50) (50) (50) (50)
Angiectasis, Focal 1 (2%)
Atrophy, Focal 1 (2%)
Basophilic Focus 31 (62%) 26 (52%) 30 (60%) 36 (72%)
Clear Cell Focus 31 (62%) 28 (56%) 29 (58%) 31 (62%)
Congestion 2 (4%)
Degeneration, Cystic, Focal 4 (8%) 3 (6%) 1 (2%) 7 (14%)
Eosinophilic Focus 4 (8%) 3 (6%) 7 (14%) 12 (24%)
Fibrosis 1 (2%)
Hepatodiaphragmatic Nodule 5 (10%) 2 (4%) 5 (10%) 4 (8%)
Histiocytosis 38 (76%) 45 (90%) 50 (100%) 50 (100%)
Hyperplasia, Focal, Histiocytic 1 (2%) 1 (2%) 3 (6%)
Infiltration Cellular, Mixed Cell 15 (30%) 5 (10%) 5 (10%) 17 (34%)
Inflammation, Chronic 18 (36%) 32 (64%) 31 (62%) 36 (72%)
Inflammation, Granulomatous 1 (2%)
Mixed Cell Focus 5 (10%) 7 (14%) 11 (22%) 27 (54%)
Thrombosis 1 (2%)
Bile Duct, Dilatation, Focal 2 (4%) 2 (4%) 2 (4%) 2 (4%)
Bile Duct, Hyperplasia 48 (96%) 48 (96%) 49 (98%) 42 (84%)
Hepatocyte, Fatty Change, Focal 21 (42%) 24 (48%) 37 (74%) 33 (66%)
Hepatocyte, Necrosis, Focal 2 (4%) 1 (2%)
Hepatocyte, Vacuolization Cytoplasmic 11 (22%) 14 (28%) 12 (24%) 18 (36%)
Serosa, Inflammation, Chronic, Focal 1 (2%)
Mesentery (13) (10) (11) (10)
Inflammation, Chronic 1 (9%) 1 (10%)
Artery, Thrombosis 1 (10%)
Fat, Hemorrhage, Focal 1 (8%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 9
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Fat, Necrosis, Focal 9 (69%) 4 (40%) 6 (55%) 5 (50%)
Oral Mucosa (1) (1) (1)
Foreign Body 1 (100%)
Hyperplasia, Focal, Squamous 1 (100%)
Inflammation, Chronic, Focal 1 (100%)
Pancreas (50) (48) (48) (49)
Angiectasis 1 (2%)
Inflammation, Chronic 1 (2%)
Acinus, Atrophy, Diffuse 1 (2%)
Acinus, Atrophy, Focal 23 (46%) 24 (50%) 24 (50%) 25 (51%)
Duct, Cyst, Focal, Multiple 15 (30%) 12 (25%) 16 (33%) 10 (20%)
Salivary Glands (50) (50) (50) (50)
Atrophy, Focal 1 (2%)
Inflammation, Chronic 1 (2%)
Stomach, Forestomach (50) (50) (50) (49)
Diverticulum 1 (2%)
Edema 3 (6%)
Hyperkeratosis, Focal 1 (2%)
Inflammation 1 (2%) 1 (2%) 3 (6%)
Ulcer 5 (10%) 2 (4%) 2 (4%) 3 (6%)
Epithelium, Hyperplasia 4 (8%) 3 (6%) 2 (4%) 4 (8%)
Stomach, Glandular (50) (50) (49) (49)
Cyst 1 (2%)
Edema 2 (4%)
Erosion 3 (6%) 1 (2%) 1 (2%) 6 (12%)
Hyperplasia, Focal, Histiocytic 1 (2%)
Inflammation, Focal 1 (2%)
Ulcer 1 (2%) 1 (2%) 2 (4%)
Epithelium, Hyperplasia 1 (2%)
Tongue (3) (1) (1)
Epithelium, Cyst 1 (33%)
Epithelium, Hyperplasia 1 (100%) 1 (100%)
Tooth (1) (1)
Peridontal Tissue, Inflammation 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Cardiomyopathy 40 (80%) 38 (76%) 36 (72%) 39 (78%)
Thrombosis 1 (2%) 3 (6%) 1 (2%) 4 (8%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 10
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50)
Accessory Adrenal Cortical Nodule 9 (18%) 6 (12%) 5 (10%) 9 (18%)
Angiectasis 1 (2%)
Cytoplasmic Alteration, Focal 3 (6%) 2 (4%) 1 (2%) 2 (4%)
Degeneration, Cystic 1 (2%)
Hematopoietic Cell Proliferation 1 (2%)
Hemorrhage, Focal 1 (2%)
Hyperplasia, Focal 1 (2%)
Necrosis 1 (2%) 1 (2%) 1 (2%)
Vacuolization Cytoplasmic, Focal 6 (12%) 5 (10%) 13 (26%) 7 (14%)
Capsule, Hyperplasia, Focal 1 (2%)
Adrenal Medulla (50) (50) (50) (50)
Hyperplasia, Focal 7 (14%) 1 (2%) 3 (6%)
Necrosis 1 (2%)
Islets, Pancreatic (50) (49) (49) (49)
Hyperplasia 1 (2%) 1 (2%)
Parathyroid Gland (48) (50) (48) (50)
Hyperplasia, Focal 1 (2%) 2 (4%)
Pituitary Gland (49) (49) (48) (48)
Angiectasis 1 (2%) 4 (8%) 1 (2%)
Cyst 4 (8%) 2 (4%) 6 (13%) 1 (2%)
Fibrosis, Focal 1 (2%)
Hemorrhage 1 (2%)
Pars Distalis, Cytoplasmic Alteration, Focal 2 (4%)
Pars Distalis, Degeneration, Cystic, Focal 1 (2%)
Pars Distalis, Hemorrhage, Focal 2 (4%)
Pars Distalis, Hyperplasia 1 (2%)
Pars Distalis, Hyperplasia, Focal 3 (6%) 1 (2%) 1 (2%) 1 (2%)
Pars Distalis, Hypertrophy, Focal 8 (16%) 9 (18%) 20 (42%) 22 (46%)
Pars Nervosa, Inflammation 1 (2%)
Thyroid Gland (47) (46) (48) (44)
C-Cell, Hyperplasia 41 (87%) 28 (61%) 26 (54%) 29 (66%)
Follicle, Cyst 3 (7%) 1 (2%) 5 (11%)
Follicle, Degeneration, Focal 6 (13%) 4 (9%) 8 (17%) 4 (9%)
Follicle, Mineralization 3 (6%) 3 (7%) 5 (10%) 6 (14%)
Follicular Cell, Hyperplasia, Focal 1 (2%) 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Peritoneum (2) (3) (1)
Inflammation, Chronic, Focal 1 (33%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 11
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM - CONT
Tissue NOS (6) (4) (6) (5)
Inflammation, Chronic 1 (20%)
Mediastinum, Cyst 1 (17%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Coagulating Gland (1)
Inflammation, Chronic 1 (100%)
Epididymis (50) (50) (50) (50)
Granuloma Sperm 1 (2%) 1 (2%)
Hemorrhage 1 (2%)
Inflammation, Chronic 1 (2%)
Spermatocele 1 (2%)
Preputial Gland (50) (50) (50) (49)
Degeneration, Cystic 5 (10%) 3 (6%) 2 (4%) 3 (6%)
Fibrosis 1 (2%)
Hyperplasia, Cystic 3 (6%) 1 (2%)
Inflammation, Chronic 30 (60%) 28 (56%) 21 (42%) 23 (47%)
Prostate (50) (50) (50) (49)
Inflammation, Chronic 27 (54%) 24 (48%) 28 (56%) 36 (73%)
Epithelium, Hyperplasia, Focal 4 (8%) 6 (12%) 5 (10%)
Seminal Vesicle (50) (50) (50) (50)
Dilatation 1 (2%)
Testes (50) (50) (50) (50)
Atrophy 15 (30%) 10 (20%) 8 (16%) 10 (20%)
Cyst 1 (2%)
Interstitial Cell, Hyperplasia, Focal 4 (8%) 6 (12%) 7 (14%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (47) (50) (48) (50)
Angiectasis 1 (2%)
Atrophy 1 (2%)
Hyperplasia 2 (4%) 3 (6%) 2 (4%) 4 (8%)
Lymph Node (19) (18) (26) (27)
Hyperplasia, Plasma Cell 1 (6%)
Deep Cervical, Hyperplasia, Histiocytic 1 (4%)
Deep Cervical, Hyperplasia, Plasma Cell 1 (5%)
Mediastinal, Ectasia 2 (11%) 2 (11%) 3 (11%)
Mediastinal, Hemorrhage 3 (16%) 2 (11%) 2 (8%) 3 (11%)
Mediastinal, Hyperplasia 1 (6%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 12
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Mediastinal, Hyperplasia, Histiocytic 5 (26%) 2 (8%) 3 (11%)
Mediastinal, Hyperplasia, Plasma Cell 2 (11%) 2 (11%) 2 (8%) 1 (4%)
Pancreatic, Ectasia 1 (5%)
Pancreatic, Fibrosis 1 (4%)
Pancreatic, Hemorrhage 1 (6%) 3 (12%) 1 (4%)
Pancreatic, Hyperplasia, Histiocytic 2 (11%) 1 (4%) 4 (15%)
Lymph Node, Mesenteric (50) (48) (48) (49)
Ectasia 1 (2%) 1 (2%)
Hemorrhage 1 (2%)
Hyperplasia, Histiocytic 2 (4%) 1 (2%) 2 (4%)
Hyperplasia, Lymphoid 1 (2%)
Spleen (50) (48) (48) (49)
Accessory Spleen 3 (6%) 1 (2%) 3 (6%)
Atrophy 3 (6%)
Fibrosis, Diffuse 1 (2%)
Fibrosis, Focal 2 (4%) 2 (4%) 2 (4%)
Hematopoietic Cell Proliferation 1 (2%) 1 (2%) 1 (2%) 1 (2%)
Hemorrhage 1 (2%) 1 (2%)
Hyperplasia, Lymphoid 1 (2%) 1 (2%)
Infarct 1 (2%) 2 (4%)
Inflammation, Granulomatous 2 (4%) 1 (2%) 2 (4%)
Thymus (48) (49) (46) (45)
Angiectasis 1 (2%)
Hemorrhage 2 (4%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (47) (46) (41) (45)
Dilatation 12 (26%) 7 (15%) 1 (2%) 2 (4%)
Fibrosis 1 (2%) 1 (2%)
Inflammation, Chronic, Focal 1 (2%)
Skin (50) (50) (50) (50)
Cyst Epithelial Inclusion 1 (2%) 1 (2%) 2 (4%) 1 (2%)
Hyperkeratosis, Focal 1 (2%) 1 (2%)
Inflammation, Focal 1 (2%)
Ulcer 1 (2%)
Epidermis, Hyperplasia, Focal 1 (2%) 1 (2%)
Subcutaneous Tissue, Edema 1 (2%)
Subcutaneous Tissue, Fibrosis, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 13
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50)
Vertebra, Cyst 1 (2%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Compression, Focal 4 (8%) 6 (12%) 1 (2%) 1 (2%)
Hemorrhage, Focal 1 (2%) 4 (8%) 3 (6%) 3 (6%)
Meninges, Congestion, Focal 1 (2%)
Meninges, Hemorrhage, Focal 1 (2%)
Spinal Cord (2) (3) (2) (3)
Hemorrhage, Focal 1 (33%) 1 (33%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Congestion 4 (8%) 1 (2%) 2 (4%)
Hemorrhage, Focal 4 (8%) 1 (2%) 3 (6%)
Infiltration Cellular, Mixed Cell 3 (6%) 1 (2%) 2 (4%)
Inflammation, Chronic, Focal 3 (6%) 3 (6%) 4 (8%) 2 (4%)
Inflammation, Focal 1 (2%)
Alveolar Epithelium, Hyperplasia, Focal 2 (4%) 4 (8%) 3 (6%)
Alveolus, Proteinosis 1 (2%)
Nose (49) (50) (50) (50)
Foreign Body 1 (2%) 1 (2%) 1 (2%)
Hemorrhage 1 (2%)
Inflammation, Suppurative 2 (4%) 1 (2%) 4 (8%) 2 (4%)
Nasolacrimal Duct, Inflammation 4 (8%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (48) (47) (48) (45)
Cataract 2 (4%) 1 (2%) 2 (4%)
Anterior Chamber, Exudate 1 (2%) 2 (4%)
Retina, Degeneration 2 (4%)
Harderian Gland (50) (50) (50) (50)
Hyperplasia, Focal, Histiocytic 1 (2%)
Hyperplasia, Focal, Lymphoid 1 (2%)
Inflammation 2 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 14
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04
Route: DOSED FEED Time: 08:36:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Inflammation, Chronic 1 (2%)
Epithelium, Hyperplasia, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (48) (49) (48) (50)
Congestion 1 (2%)
Cyst 2 (4%) 1 (2%)
Infarct 2 (4%) 1 (2%) 4 (8%)
Nephropathy 47 (98%) 43 (88%) 47 (98%) 46 (92%)
Pelvis, Dilatation 1 (2%) 1 (2%)
Renal Tubule, Accumulation, Hyaline Droplet 1 (2%) 3 (6%) 2 (4%) 2 (4%)
Renal Tubule, Hyperplasia, Focal 1 (2%)
Renal Tubule, Pigmentation 1 (2%) 1 (2%) 2 (4%)
Urethra (1)
Muscularis, Inflammation, Chronic 1 (100%)
Urinary Bladder (49) (50) (50) (50)
Hemorrhage 1 (2%) 1 (2%) 1 (2%)
Inflammation 1 (2%) 1 (2%)
Ulcer 1 (2%)
Muscularis, Hyperplasia 1 (2%)
Transitional Epithelium, Hyperplasia 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 15
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