TDMS Study 92013-05 Pathology Tables
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
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
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 1
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
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 [3.0]
Liver (50) (50) (48) (50)
Basophilic Focus 46 43 31 25
Clear Cell Focus 20 32 23 27
Congestion 2 [3.0] 2 [2.5] 1 [3.0]
Degeneration, Cystic, Focal 1 [1.0] 1 [3.0] 3 [3.0]
Eosinophilic Focus 1 2 5 11
Hematopoietic Cell Proliferation 1 [3.0]
Hemorrhage 1 [2.0]
Hepatodiaphragmatic Nodule 5 4 6 11
Histiocytosis 40 [1.0] 50 [1.3] 48 [1.9] 50 [2.5]
Hyperplasia, Focal, Histiocytic 2 [2.0]
Infiltration Cellular, Mixed Cell 5 [1.0] 5 [1.4] 5 [1.6]
Inflammation, Chronic 17 [1.2] 28 [1.5] 34 [1.8] 35 [1.7]
Inflammation, Chronic, Focal 1 [1.0]
Inflammation, Granulomatous 1 [1.0]
Mixed Cell Focus 10 7 6 18
Thrombosis 1 [2.0]
Bile Duct, Cyst 1
Bile Duct, Dilatation, Focal 2 [2.5] 1 [2.0]
Bile Duct, Hyperplasia 31 [1.5] 38 [1.6] 43 [1.9] 35 [1.9]
Hepatocyte, Fatty Change, Focal 16 [1.2] 29 [1.6] 29 [2.0] 32 [2.2]
Hepatocyte, Hyperplasia, Focal 1 [3.0]
Hepatocyte, Necrosis, Focal 1 [2.0] 1 [2.0]
Hepatocyte, Vacuolization Cytoplasmic 6 [2.7] 12 [2.3] 17 [2.4] 11 [2.4]
Hepatocyte, Centrilobular, Necrosis 2 [3.0] 1 [3.0] 1 [4.0]
Oval Cell, Hyperplasia, Focal 1 [2.0] 2 [2.0]
Serosa, Fibrosis 1 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 2
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Mesentery (9) (7) (11) (8)
Inflammation, Chronic 1 [3.0] 1 [1.0]
Fat, Necrosis, Focal 8 [2.5] 3 [2.0] 1 [1.0]
Lymphatic, Angiectasis 1 [2.0]
Pancreas (49) (49) (47) (47)
Acinus, Atrophy, Diffuse 1 [4.0]
Acinus, Atrophy, Focal 13 [1.3] 22 [1.7] 26 [1.8] 30 [1.7]
Duct, Cyst, Focal, Multiple 10 [1.5] 18 [2.0] 11 [1.4] 9 [1.7]
Salivary Glands (50) (50) (50) (50)
Atrophy, Focal 2 [1.5]
Inflammation, Chronic 1 [4.0] 1 [3.0] 1 [3.0]
Stomach, Forestomach (50) (50) (49) (50)
Diverticulum 1
Edema 1 [3.0] 1 [3.0] 2 [3.0] 1 [3.0]
Inflammation 2 [2.0]
Ulcer 1 [1.0] 1 [2.0] 3 [1.7] 2 [1.0]
Epithelium, Hyperplasia 1 [2.0] 6 [2.0] 1 [1.0]
Stomach, Glandular (50) (50) (49) (49)
Erosion 2 [2.0] 1 [2.0] 1 [3.0] 4 [1.5]
Ulcer 1 [2.0]
Tongue (5) (4) (3)
Epithelium, Hyperplasia 1 [2.0] 1 [1.0]
Tooth (1) (1) (2)
Malformation 1 [2.0] 2 [2.0]
Peridontal Tissue, Inflammation 1 [4.0] 1 [3.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (48) (50)
Cardiomyopathy 30 [1.3] 43 [1.5] 38 [1.8] 44 [1.9]
Inflammation, Focal, Suppurative 1 [2.0]
Thrombosis 2 [3.0] 5 [3.4]
Artery, Inflammation, Chronic 1 [2.0]
Epicardium, Inflammation 1 [3.0]
Myocardium, Fibrosis, Focal 1 [2.0]
Pericardium, Infiltration Cellular, Mixed
Cell 1 [1.0]
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (50) (50) (50)
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 3
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Accessory Adrenal Cortical Nodule 8 [1.3] 6 [1.2] 3 [1.3] 2 [1.0]
Angiectasis 4 [2.5] 2 [2.5] 7 [2.6] 4 [2.8]
Cytoplasmic Alteration, Focal 1 [2.0] 2 [1.0] 2 [1.5] 2 [2.0]
Hematopoietic Cell Proliferation 1 [1.0]
Hemorrhage, Focal 2 [3.0] 1 [3.0]
Vacuolization Cytoplasmic, Focal 8 [2.3] 9 [2.0] 13 [2.2] 12 [1.6]
Adrenal Medulla (48) (50) (50) (50)
Angiectasis 1 [2.0] 1 [2.0]
Atrophy 1 [3.0]
Hyperplasia, Focal 2 [1.0] 2 [2.5]
Hyperplasia, Lymphoid 1 [3.0]
Islets, Pancreatic (49) (50) (48) (47)
Atrophy 1 [3.0]
Parathyroid Gland (50) (49) (48) (49)
Hyperplasia, Focal 1 [2.0]
Pituitary Gland (48) (50) (50) (50)
Angiectasis 6 [2.8] 4 [2.3] 3 [2.0] 4 [2.5]
Cyst 4 2 5
Hyperplasia, Focal, Histiocytic 1 [2.0]
Pars Distalis, Angiectasis 1 [3.0] 2 [1.0] 3 [2.0]
Pars Distalis, Degeneration, Cystic, Focal 9 [1.9] 6 [2.5] 5 [1.8] 3 [1.7]
Pars Distalis, Hemorrhage, Focal 1 [2.0]
Pars Distalis, Hyperplasia, Focal 4 [1.8] 4 [2.3] 5 [2.4] 4 [2.0]
Pars Distalis, Hypertrophy, Focal 1 [3.0] 1 [2.0] 4 [1.5]
Thyroid Gland (47) (44) (40) (45)
C-Cell, Hyperplasia 45 [2.0] 42 [1.7] 36 [1.9] 35 [1.7]
Follicle, Cyst 1
Follicle, Degeneration, Focal 1 [1.0] 1 [1.0]
Follicle, Mineralization 2 [1.0] 7 [1.0] 6 [1.0] 19 [1.0]
Follicular Cell, Hyperplasia, Focal 1 [2.0] 1 [2.0] 1 [2.0] 2 [2.0]
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (5) (3) (6) (6)
Fibrosis, Focal 1 [2.0]
Mediastinum, Cyst 1 [2.0]
Mediastinum, Infiltration Cellular, Mixed
Cell 1 [1.0]
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 4
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT
Clitoral Gland (50) (50) (50) (50)
Degeneration, Cystic 4 [2.3] 5 [3.0] 3 [2.3]
Hyperplasia, Cystic 7 [2.4] 4 [2.3] 1 [2.0] 1 [3.0]
Hyperplasia, Focal, Histiocytic 1 [2.0]
Inflammation, Chronic 2 [2.0] 2 [1.5] 3 [1.7]
Ovary (50) (50) (48) (50)
Angiectasis 2 [3.0]
Cyst 7 3 5
Periovarian Tissue, Hemorrhage 1 [3.0]
Uterus (50) (50) (48) (50)
Inflammation, Chronic, Granulomatous 1 [3.0]
Ulcer 1 [4.0]
Cervix, Hypertrophy 1 [3.0]
Endometrium, Hyperplasia, Cystic 25 [1.5] 26 [1.9] 18 [2.1] 26 [1.5]
Vagina (1) (2) (5) (4)
Angiectasis 1 [3.0]
Infiltration Cellular, Polymorphonuclear 1 [2.0] 1 [2.0]
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (48) (49) (48)
Atrophy 2 [3.0]
Fibrosis 1 [3.0] 1 [3.0]
Hyperplasia 3 [3.0] 2 [3.0] 1 [3.0] 2 [2.5]
Hyperplasia, Focal, Histiocytic 1 [2.0] 2 [2.0] 3 [2.0]
Erythroid Cell, Hyperplasia 1 [3.0]
Lymph Node (24) (11) (24) (35)
Hyperplasia, Plasma Cell 1 [3.0]
Deep Cervical, Hemorrhage 3 [3.0]
Mediastinal, Congestion 1 [3.0]
Mediastinal, Ectasia 3 [3.3] 1 [3.0] 1 [3.0]
Mediastinal, Hemorrhage 5 [3.0] 3 [2.7] 5 [3.0] 3 [3.0]
Mediastinal, Hyperplasia, Histiocytic 4 [3.0] 1 [3.0] 1 [3.0] 6 [3.0]
Mediastinal, Hyperplasia, Lymphoid 1 [3.0] 1 [3.0]
Mediastinal, Hyperplasia, Plasma Cell 1 [3.0]
Mediastinal, Pigmentation 1 [3.0]
Pancreatic, Hemorrhage 1 [2.0] 2 [2.5] 2 [3.0]
Pancreatic, Hyperplasia, Histiocytic 6 [2.8] 1 [3.0] 7 [3.0] 7 [3.1]
Pancreatic, Hyperplasia, Lymphoid 1 [3.0]
Pancreatic, Hyperplasia, Plasma Cell 1 [3.0]
Pancreatic, Pigmentation 1 [2.0]
Renal, Hyperplasia, Histiocytic 1 [3.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 5
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Lymph Node, Mandibular (1) (3) (1) (4)
Ectasia 1 [3.0]
Hyperplasia, Histiocytic 1 [3.0]
Hyperplasia, Lymphoid 1 [3.0]
Lymph Node, Mesenteric (49) (49) (49) (47)
Ectasia 2 [3.0]
Hemorrhage 1 [3.0]
Hyperplasia, Histiocytic 7 [3.0] 1 [3.0] 2 [3.0]
Hyperplasia, Lymphoid 1 [3.0]
Spleen (50) (48) (47) (48)
Accessory Spleen 3 1 1
Atrophy 2 [2.5]
Congestion 1 [3.0]
Fibrosis, Focal 1 [3.0] 1 [3.0] 1 [2.0]
Hematopoietic Cell Proliferation 6 [3.0] 2 [2.5]
Inflammation, Granulomatous 3 [2.7] 10 [3.2] 3 [1.7]
Stromal Hyperplasia 1 [3.0]
Capsule, Infiltration Cellular, Focal, Mixed
Cell 2 [2.0] 1 [1.0]
Thymus (47) (50) (48) (48)
Angiectasis 1 [2.0]
Cyst 2 [2.5]
Hemorrhage 1 [3.0]
Hyperplasia, Lymphoid 1 [4.0] 1 [2.0] 1 [3.0]
Epithelial Cell, Hyperplasia 1 [3.0]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (49) (50) (50)
Dilatation 37 [2.7] 16 [2.3] 8 [2.0] 1 [2.0]
Fibrosis 1 [3.0]
Hyperplasia 6 [2.5] 3 [1.7] 3 [1.7] 1 [2.0]
Skin (50) (50) (50) (50)
Inflammation, Focal 1 [2.0]
Ulcer 1 [2.0] 1 [3.0] 1 [3.0]
Epidermis, Hyperplasia, Focal 1 [1.0] 2 [2.5]
Lip, Cyst Epithelial Inclusion 1 [2.0]
Pinna, Inflammation, Chronic, Focal 1 [2.0]
Subcutaneous Tissue, Edema 1 [3.0] 1 [2.0] 1 [3.0]
Subcutaneous Tissue, Fibrosis, Focal 1 [2.0]
Subcutaneous Tissue, Hemorrhage, Focal 1 [2.0]
Subcutaneous Tissue, Necrosis, Fatty, Focal 1 [3.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 6
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
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 [2.8] 8 [3.0] 8 [3.0] 2 [2.5]
Hemorrhage, Focal 1 [2.0] 2 [3.0] 4 [2.0] 2 [1.5]
Meninges, Hemorrhage, Focal 1 [3.0]
Thalamus, Mineralization, Focal 1 [2.0] 1 [2.0]
Spinal Cord (7) (3) (24) (50)
Hemorrhage, Focal 2 [3.0]
Necrosis, Focal 1 [3.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Congestion 1 [2.0] 5 [2.2] 3 [3.0] 5 [2.2]
Hemorrhage, Focal 1 [3.0] 2 [3.0] 2 [2.0]
Hyperplasia, Focal, Histiocytic 1 [2.0] 2 [3.0]
Infiltration Cellular, Mixed Cell 3 [1.7] 1 [1.0] 1 [3.0]
Inflammation, Chronic, Focal 25 [1.1] 40 [1.2] 39 [1.0] 43 [1.2]
Alveolar Epithelium, Hyperplasia, Focal 4 [2.0] 3 [1.3] 2 [1.5]
Interstitium, Edema 1 [2.0] 1 [2.0]
Mediastinum, Congestion 1 [3.0]
Mediastinum, Edema 1 [2.0] 1 [2.0] 1 [3.0]
Mediastinum, Mineralization, Focal 1 [3.0]
Nose (49) (50) (50) (50)
Foreign Body 2 [1.5]
Inflammation, Suppurative 3 [2.0] 1 [2.0]
Nasolacrimal Duct, Hemorrhage 1 [1.0]
Nasolacrimal Duct, Inflammation 2 [2.5] 5 [2.0] 4 [2.0] 5 [2.6]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (48) (45) (40) (45)
Atrophy 3 [3.3] 4 [3.3]
Cataract 4 [2.8] 1 [2.0] 1 [3.0]
Inflammation, Chronic 1 [4.0] 1 [3.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 7
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Synechia 1 [3.0] 2 [3.0]
Anterior Chamber, Exudate 1 [3.0] 1 [3.0]
Cornea, Inflammation, Chronic 1 [4.0]
Cornea, Necrosis, Focal 1 [4.0] 1 [4.0] 2 [3.5]
Retina, Degeneration 4 [3.0] 1 [3.0] 3 [3.0]
Harderian Gland (50) (50) (50) (50)
Cytoplasmic Alteration, Focal 1 [1.0]
Hyperplasia, Focal, Histiocytic 1 [1.0] 4 [1.5] 5 [1.2]
Inflammation 1 [1.0] 1 [1.0]
Epithelium, Hyperplasia, Focal 1 [1.0]
Zymbal's Gland (3) (1)
Cyst 1 [4.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (48) (48) (43) (43)
Cyst 2 [2.5]
Hydronephrosis 1 [2.0]
Infarct 1 [2.0] 1 [2.0] 1 [4.0] 2 [2.0]
Mineralization, Focal 1 [2.0]
Nephropathy 45 [1.1] 37 [1.1] 36 [1.1] 38 [1.4]
Pelvis, Dilatation 1 [3.0]
Renal Tubule, Accumulation, Hyaline Droplet 3 [2.7] 2 [2.5] 1 [3.0]
Renal Tubule, Hyperplasia, Focal 1 [2.0]
Renal Tubule, Pigmentation 2 [3.0]
Urinary Bladder (49) (50) (49) (48)
Hemorrhage 1 [1.0] 2 [3.0]
Inflammation 1 [3.0] 1 [2.0]
Transitional Epithelium, Hyperplasia 1 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 8
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
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 [3.0]
Edema 1 [3.0]
Liver (50) (50) (50) (50)
Angiectasis, Focal 1 [2.0]
Atrophy, Focal 1 [2.0]
Basophilic Focus 31 26 30 36
Clear Cell Focus 31 28 29 31
Congestion 2 [2.0]
Degeneration, Cystic, Focal 4 [1.3] 3 [1.3] 1 [2.0] 7 [2.0]
Eosinophilic Focus 4 3 7 12
Fibrosis 1 [2.0]
Hepatodiaphragmatic Nodule 5 2 5 4
Histiocytosis 38 [1.1] 45 [1.4] 50 [1.9] 50 [2.3]
Hyperplasia, Focal, Histiocytic 1 [1.0] 1 [2.0] 3 [2.0]
Infiltration Cellular, Mixed Cell 15 [1.2] 5 [1.2] 5 [1.6] 17 [1.1]
Inflammation, Chronic 18 [1.1] 32 [1.2] 31 [1.3] 36 [1.3]
Inflammation, Granulomatous 1 [1.0]
Mixed Cell Focus 5 7 11 27
Thrombosis 1 [3.0]
Bile Duct, Dilatation, Focal 2 [1.5] 2 [2.0] 2 [1.5] 2 [1.5]
Bile Duct, Hyperplasia 48 [2.8] 48 [2.9] 49 [2.9] 42 [3.0]
Hepatocyte, Fatty Change, Focal 21 [1.5] 24 [1.8] 37 [1.9] 33 [2.5]
Hepatocyte, Necrosis, Focal 2 [2.0] 1 [2.0]
Hepatocyte, Vacuolization Cytoplasmic 11 [2.2] 14 [2.9] 12 [2.3] 18 [2.3]
Serosa, Inflammation, Chronic, Focal 1 [2.0]
Mesentery (13) (10) (11) (10)
Inflammation, Chronic 1 [2.0] 1 [3.0]
Artery, Thrombosis 1 [3.0]
Fat, Hemorrhage, Focal 1 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 9
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Fat, Necrosis, Focal 9 [2.8] 4 [3.0] 6 [3.0] 5 [2.8]
Oral Mucosa (1) (1) (1)
Foreign Body 1 [3.0]
Hyperplasia, Focal, Squamous 1 [2.0]
Inflammation, Chronic, Focal 1 [3.0]
Pancreas (50) (48) (48) (49)
Angiectasis 1 [3.0]
Inflammation, Chronic 1 [3.0]
Acinus, Atrophy, Diffuse 1 [3.0]
Acinus, Atrophy, Focal 23 [1.7] 24 [1.7] 24 [2.1] 25 [1.9]
Duct, Cyst, Focal, Multiple 15 [1.7] 12 [1.8] 16 [1.9] 10 [1.9]
Salivary Glands (50) (50) (50) (50)
Atrophy, Focal 1 [2.0]
Inflammation, Chronic 1 [2.0]
Stomach, Forestomach (50) (50) (50) (49)
Diverticulum 1 [2.0]
Edema 3 [3.0]
Hyperkeratosis, Focal 1 [2.0]
Inflammation 1 [2.0] 1 [2.0] 3 [2.0]
Ulcer 5 [2.0] 2 [3.0] 2 [2.5] 3 [2.3]
Epithelium, Hyperplasia 4 [2.5] 3 [2.7] 2 [2.0] 4 [1.8]
Stomach, Glandular (50) (50) (49) (49)
Cyst 1 [2.0]
Edema 2 [2.5]
Erosion 3 [1.7] 1 [2.0] 1 [1.0] 6 [1.8]
Hyperplasia, Focal, Histiocytic 1 [1.0]
Inflammation, Focal 1 [2.0]
Ulcer 1 [2.0] 1 [3.0] 2 [2.5]
Epithelium, Hyperplasia 1 [2.0]
Tongue (3) (1) (1)
Epithelium, Cyst 1 [2.0]
Epithelium, Hyperplasia 1 [1.0] 1 [1.0]
Tooth (1) (1)
Peridontal Tissue, Inflammation 1 [3.0] 1 [3.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Cardiomyopathy 40 [1.7] 38 [1.7] 36 [1.6] 39 [1.8]
Thrombosis 1 [4.0] 3 [3.0] 1 [3.0] 4 [2.8]
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 10
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
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 [1.2] 6 [1.2] 5 [1.2] 9 [1.0]
Angiectasis 1 [2.0]
Cytoplasmic Alteration, Focal 3 [1.0] 2 [1.5] 1 [2.0] 2 [1.0]
Degeneration, Cystic 1 [4.0]
Hematopoietic Cell Proliferation 1 [3.0]
Hemorrhage, Focal 1 [2.0]
Hyperplasia, Focal 1 [1.0]
Necrosis 1 [2.0] 1 [4.0] 1 [2.0]
Vacuolization Cytoplasmic, Focal 6 [1.3] 5 [1.4] 13 [1.4] 7 [1.3]
Capsule, Hyperplasia, Focal 1 [2.0]
Adrenal Medulla (50) (50) (50) (50)
Hyperplasia, Focal 7 [1.4] 1 [1.0] 3 [1.3]
Necrosis 1 [3.0]
Islets, Pancreatic (50) (49) (49) (49)
Hyperplasia 1 [2.0] 1 [2.0]
Parathyroid Gland (48) (50) (48) (50)
Hyperplasia, Focal 1 [2.0] 2 [2.5]
Pituitary Gland (49) (49) (48) (48)
Angiectasis 1 [2.0] 4 [2.5] 1 [3.0]
Cyst 4 2 6 1
Fibrosis, Focal 1 [3.0]
Hemorrhage 1 [3.0]
Pars Distalis, Cytoplasmic Alteration, Focal 2 [1.5]
Pars Distalis, Degeneration, Cystic, Focal 1 [2.0]
Pars Distalis, Hemorrhage, Focal 2 [2.5]
Pars Distalis, Hyperplasia 1 [3.0]
Pars Distalis, Hyperplasia, Focal 3 [2.3] 1 [2.0] 1 [2.0] 1 [2.0]
Pars Distalis, Hypertrophy, Focal 8 [1.8] 9 [1.6] 20 [1.8] 22 [2.0]
Pars Nervosa, Inflammation 1 [1.0]
Thyroid Gland (47) (46) (48) (44)
C-Cell, Hyperplasia 41 [1.5] 28 [1.6] 26 [1.5] 29 [1.7]
Follicle, Cyst 3 1 5
Follicle, Degeneration, Focal 6 [1.0] 4 [1.5] 8 [1.3] 4 [1.3]
Follicle, Mineralization 3 [1.0] 3 [1.0] 5 [1.0] 6 [1.0]
Follicular Cell, Hyperplasia, Focal 1 [1.0] 1 [1.0] 1 [2.0]
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Peritoneum (2) (3) (1)
Inflammation, Chronic, Focal 1 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 11
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
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 [3.0]
Mediastinum, Cyst 1 [2.0]
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Coagulating Gland (1)
Inflammation, Chronic 1 [2.0]
Epididymis (50) (50) (50) (50)
Granuloma Sperm 1 [3.0] 1 [3.0]
Hemorrhage 1 [3.0]
Inflammation, Chronic 1 [2.0]
Spermatocele 1 [3.0]
Preputial Gland (50) (50) (50) (49)
Degeneration, Cystic 5 [2.8] 3 [2.7] 2 [2.5] 3 [2.7]
Fibrosis 1 [3.0]
Hyperplasia, Cystic 3 [2.3] 1 [2.0]
Inflammation, Chronic 30 [1.6] 28 [1.6] 21 [1.9] 23 [1.7]
Prostate (50) (50) (50) (49)
Inflammation, Chronic 27 [1.7] 24 [2.0] 28 [1.6] 36 [2.0]
Epithelium, Hyperplasia, Focal 4 [1.3] 6 [1.3] 5 [1.2]
Seminal Vesicle (50) (50) (50) (50)
Dilatation 1 [3.0]
Testes (50) (50) (50) (50)
Atrophy 15 [3.0] 10 [2.8] 8 [3.0] 10 [3.1]
Cyst 1 [3.0]
Interstitial Cell, Hyperplasia, Focal 4 [1.8] 6 [1.8] 7 [1.6]
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (47) (50) (48) (50)
Angiectasis 1 [3.0]
Atrophy 1 [3.0]
Hyperplasia 2 [3.0] 3 [2.7] 2 [3.0] 4 [2.5]
Lymph Node (19) (18) (26) (27)
Hyperplasia, Plasma Cell 1 [3.0]
Deep Cervical, Hyperplasia, Histiocytic 1 [3.0]
Deep Cervical, Hyperplasia, Plasma Cell 1 [3.0]
Mediastinal, Ectasia 2 [3.0] 2 [2.0] 3 [3.0]
Mediastinal, Hemorrhage 3 [3.0] 2 [3.0] 2 [3.0] 3 [3.0]
Mediastinal, Hyperplasia 1 [3.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 12
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Mediastinal, Hyperplasia, Histiocytic 5 [3.0] 2 [3.0] 3 [3.0]
Mediastinal, Hyperplasia, Plasma Cell 2 [3.0] 2 [4.0] 2 [3.0] 1 [3.0]
Pancreatic, Ectasia 1 [2.0]
Pancreatic, Fibrosis 1 [3.0]
Pancreatic, Hemorrhage 1 [3.0] 3 [2.3] 1 [3.0]
Pancreatic, Hyperplasia, Histiocytic 2 [2.5] 1 [3.0] 4 [3.0]
Lymph Node, Mesenteric (50) (48) (48) (49)
Ectasia 1 [3.0] 1 [3.0]
Hemorrhage 1 [3.0]
Hyperplasia, Histiocytic 2 [3.0] 1 [3.0] 2 [3.0]
Hyperplasia, Lymphoid 1 [2.0]
Spleen (50) (48) (48) (49)
Accessory Spleen 3 1 3
Atrophy 3 [2.3]
Fibrosis, Diffuse 1 [3.0]
Fibrosis, Focal 2 [3.0] 2 [3.0] 2 [3.0]
Hematopoietic Cell Proliferation 1 [3.0] 1 [3.0] 1 [2.0] 1 [2.0]
Hemorrhage 1 [4.0] 1 [3.0]
Hyperplasia, Lymphoid 1 [2.0] 1 [3.0]
Infarct 1 [3.0] 2 [3.0]
Inflammation, Granulomatous 2 [3.0] 1 [1.0] 2 [2.0]
Thymus (48) (49) (46) (45)
Angiectasis 1 [3.0]
Hemorrhage 2 [2.5]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (47) (46) (41) (45)
Dilatation 12 [2.3] 7 [2.6] 1 [2.0] 2 [3.0]
Fibrosis 1 [2.0] 1 [3.0]
Inflammation, Chronic, Focal 1 [2.0]
Skin (50) (50) (50) (50)
Cyst Epithelial Inclusion 1 [3.0] 1 [2.0] 2 [2.5] 1 [3.0]
Hyperkeratosis, Focal 1 [2.0] 1 [2.0]
Inflammation, Focal 1 [1.0]
Ulcer 1 [3.0]
Epidermis, Hyperplasia, Focal 1 [2.0] 1 [1.0]
Subcutaneous Tissue, Edema 1 [3.0]
Subcutaneous Tissue, Fibrosis, Focal 1 [2.0]
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 13
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50)
Vertebra, Cyst 1 [4.0]
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Compression, Focal 4 [3.0] 6 [3.2] 1 [3.0] 1 [2.0]
Hemorrhage, Focal 1 [2.0] 4 [2.5] 3 [2.3] 3 [2.3]
Meninges, Congestion, Focal 1 [2.0]
Meninges, Hemorrhage, Focal 1 [2.0]
Spinal Cord (2) (3) (2) (3)
Hemorrhage, Focal 1 [1.0] 1 [2.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Congestion 4 [2.8] 1 [2.0] 2 [3.0]
Hemorrhage, Focal 4 [2.3] 1 [3.0] 3 [2.3]
Infiltration Cellular, Mixed Cell 3 [1.7] 1 [2.0] 2 [2.0]
Inflammation, Chronic, Focal 3 [1.3] 3 [2.0] 4 [1.3] 2 [1.0]
Inflammation, Focal 1 [1.0]
Alveolar Epithelium, Hyperplasia, Focal 2 [2.0] 4 [1.8] 3 [1.7]
Alveolus, Proteinosis 1 [3.0]
Nose (49) (50) (50) (50)
Foreign Body 1 [2.0] 1 [1.0] 1 [2.0]
Hemorrhage 1 [3.0]
Inflammation, Suppurative 2 [2.5] 1 [1.0] 4 [1.8] 2 [2.0]
Nasolacrimal Duct, Inflammation 4 [2.0]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (48) (47) (48) (45)
Cataract 2 [3.0] 1 [3.0] 2 [2.0]
Anterior Chamber, Exudate 1 [3.0] 2 [2.5]
Retina, Degeneration 2 [3.0]
Harderian Gland (50) (50) (50) (50)
Hyperplasia, Focal, Histiocytic 1 [3.0]
Hyperplasia, Focal, Lymphoid 1 [2.0]
Inflammation 2 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 14
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT18
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 12/06/04
Route: DOSED FEED 4-METHYLIMIDAZOLE Time: 09:00:53
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Inflammation, Chronic 1 [3.0]
Epithelium, Hyperplasia, Focal 1 [2.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (48) (49) (48) (50)
Congestion 1 [3.0]
Cyst 2 [2.0] 1 [3.0]
Infarct 2 [2.5] 1 [3.0] 4 [2.3]
Nephropathy 47 [1.6] 43 [1.6] 47 [1.4] 46 [1.7]
Pelvis, Dilatation 1 [2.0] 1 [3.0]
Renal Tubule, Accumulation, Hyaline Droplet 1 [2.0] 3 [2.0] 2 [3.0] 2 [2.0]
Renal Tubule, Hyperplasia, Focal 1 [1.0]
Renal Tubule, Pigmentation 1 [2.0] 1 [3.0] 2 [3.0]
Urethra (1)
Muscularis, Inflammation, Chronic 1 [3.0]
Urinary Bladder (49) (50) (50) (50)
Hemorrhage 1 [3.0] 1 [3.0] 1 [4.0]
Inflammation 1 [1.0] 1 [3.0]
Ulcer 1 [3.0]
Muscularis, Hyperplasia 1 [3.0]
Transitional Epithelium, Hyperplasia 1 [2.0]
a Number of animals examined microscopically at site and number of animals with lesion
b Average severity grade (1-minimal;2-mild;3-moderate;4-marked)
Page 15
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