TDMS Study 56348-04 Pathology Tables
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
Facility: Battelle Columbus Laboratory
Chemical CAS #: 5392-40-5
Lock Date: 03/25/99
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50
Early Deaths
Natural Death 5 3 3 3 5
Moribund Sacrifice 4 5 2 4 5
Accidently Killed 1
Survivors
Terminal Sacrifice 40 41 45 43 40
Missing 1
Animals Examined Microscopically 50 49 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Esophagus (50) (49) (50) (50) (50)
Hyperplasia, Basal Cell 1 [3.0]
Intestine Small, Duodenum (50) (49) (50) (50) (49)
Ectasia 1 [3.0]
Inflammation, Chronic 1 [1.0] 1 [3.0] 1 [1.0] 1 [1.0]
Ulcer 1 [3.0]
Epithelium, Hyperplasia, Focal 1 [1.0] 1 [2.0]
Epithelium, Metaplasia, Squamous 1 [1.0]
Intestine Small, Jejunum (50) (49) (50) (50) (50)
Inflammation, Chronic Active 1 [3.0]
Ulcer 1 [2.0] 1 [3.0]
Muscularis, Infiltration Cellular, Lymphocyte 1 [1.0]
Peyer's Patch, Hyperplasia, Lymphoid 2 [3.5] 2 [3.0]
Peyer's Patch, Infiltration Cellular, Plasma
Cell 1 [3.0]
Intestine Small, Ileum (50) (49) (50) (50) (50)
Inflammation, Chronic 1 [2.0]
Inflammation, Granulomatous 1 [4.0]
Ulcer 1 [4.0]
Liver (50) (49) (50) (50) (50)
Basophilic Focus 1
Clear Cell Focus 3 2 6
Eosinophilic Focus 1 1
Hematopoietic Cell Proliferation 1 [2.0] 1 [1.0] 3 [2.7]
Hemorrhage 1 [1.0] 1 [1.0]
Infarct 1 [1.0]
Infiltration Cellular, Lymphocyte 16 [1.0] 18 [1.1] 12 [1.0] 27 [1.2] 25 [1.0]
Inflammation, Granulomatous 20 [1.0] 14 [1.0] 20 [1.0] 16 [1.0] 11 [1.0]
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Mineralization 1 [3.0]
Mixed Cell Focus 4 5 1 4 3
Necrosis, Focal 2 [2.0] 3 [2.0] 2 [1.0] 3 [1.3]
Vacuolization Cytoplasmic, Focal 4 [1.0] 3 [1.0] 5 [1.0] 3 [1.0] 5 [1.0]
Bile Duct, Cyst 1 [2.0]
Bile Duct, Inflammation, Granulomatous 1 [1.0]
Centrilobular, Degeneration 1 [2.0] 1 [3.0] 1 [3.0] 1 [3.0] 2 [1.0]
Mesentery (5) (3) (1) (6) (2)
Infiltration Cellular, Mast Cell 1 [2.0]
Inflammation, Granulomatous 1 [2.0] 1 [4.0]
Thrombosis 1 [3.0]
Artery, Inflammation, Chronic 1 [3.0] 1 [2.0]
Fat, Necrosis 3 [2.3] 2 [2.0] 1 [2.0] 2 [2.0] 1 [2.0]
Oral Mucosa (50) (49) (50) (50) (50)
Infiltration Cellular, Mast Cell 1 [1.0] 1 [1.0]
Inflammation, Chronic Active 20 [1.4] 14 [1.4] 32 [1.9] 35 [1.8] 32 [1.5]
Ulcer 6 [1.3] 6 [1.2] 15 [1.9] 22 [1.6] 15 [1.5]
Pancreas (50) (49) (50) (50) (50)
Fibrosis, Focal 1 [2.0]
Hypertrophy, Focal 1 [1.0]
Infiltration Cellular, Mast Cell 1 [2.0]
Inflammation, Chronic 1 [1.0]
Acinus, Atrophy 1 [4.0] 2 [3.0]
Acinus, Hypertrophy, Focal 1 [2.0] 2 [1.0]
Duct, Cyst 2 [3.5] 1 [3.0] 1 [3.0] 1 [3.0]
Duct, Inflammation, Chronic 1 [4.0]
Salivary Glands (49) (49) (50) (50) (49)
Artery, Inflammation, Chronic 1 [2.0] 1 [2.0]
Parotid Gland, Inflammation, Chronic 1 [1.0]
Stomach, Forestomach (50) (49) (50) (50) (50)
Edema, Diffuse 1 [3.0]
Edema, Focal 1 [1.0]
Infiltration Cellular, Lymphocyte 1 [1.0]
Inflammation, Chronic, Focal 1 [2.0]
Ulcer 1 [2.0] 1 [2.0] 1 [2.0] 2 [1.5]
Epithelium, Hyperplasia, Focal 3 [1.3] 2 [2.5] 3 [2.0] 1 [1.0] 2 [2.0]
Stomach, Glandular (50) (49) (50) (50) (50)
Edema, Diffuse 1 [3.0]
Mineralization 1 [3.0]
Ulcer 1 [2.0] 1 [2.0]
Artery, Inflammation, Chronic 1 [1.0]
Epithelium, Hyperplasia, Atypical, Focal 1 [1.0]
Glands, Ectasia 1 [1.0] 1 [1.0]
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 3
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Muscularis, Inflammation, Acute 1 [2.0]
Tooth (1)
Pulp, Inflammation, Chronic 1 [2.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Blood Vessel (50) (49) (50) (50) (50)
Aorta, Mineralization 1 [4.0] 1 [3.0] 1 [2.0]
Aorta, Adventitia, Inflammation, Chronic 1 [1.0]
Pulmonary Vein, Hemorrhage 1 [2.0]
Heart (50) (49) (50) (50) (50)
Artery, Inflammation, Chronic 1 [2.0] 2 [1.0] 1 [3.0] 2 [2.0]
Artery, Mineralization 1 [3.0]
Atrium, Inflammation, Chronic 1 [1.0] 1 [2.0]
Atrium, Thrombosis 1 [1.0]
Coronary Artery, Inflammation, Chronic 1 [1.0]
Myocardium, Degeneration 3 [1.3] 1 [2.0] 1 [1.0] 1 [1.0] 1 [2.0]
Myocardium, Inflammation, Chronic 1 [1.0]
Myocardium, Mineralization 1 [2.0] 1 [1.0]
Valve, Inflammation, Chronic 2 [4.0] 2 [3.0] 4 [2.5] 1 [4.0]
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (49) (50) (50) (50)
Accessory Adrenal Cortical Nodule 1 [1.0]
Atrophy 1 [1.0]
Hematopoietic Cell Proliferation 1 [2.0] 1 [2.0] 1 [1.0]
Hyperplasia, Focal 1 [2.0] 2 [1.0] 2 [1.0]
Hypertrophy, Focal 3 [1.0] 3 [1.7] 2 [1.0] 2 [1.0] 3 [1.0]
Inflammation, Granulomatous 1 [1.0]
Vacuolization Cytoplasmic, Focal 1 [2.0]
Subcapsular, Hyperplasia 47 [1.0] 49 [1.1] 50 [1.0] 49 [1.0] 49 [1.1]
Subcapsular, Hyperplasia, Focal 1 [1.0]
Adrenal Medulla (50) (49) (50) (50) (50)
Hyperplasia, Focal 1 [1.0] 1 [1.0] 2 [2.0] 2 [1.0]
Islets, Pancreatic (50) (49) (50) (50) (50)
Hyperplasia 2 [1.0] 3 [1.3] 1 [2.0] 2 [1.5]
Parathyroid Gland (43) (42) (35) (40) (43)
Inflammation, Granulomatous 1 [1.0]
Pituitary Gland (49) (48) (50) (49) (49)
Angiectasis 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 4
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Cyst 1 [1.0] 1 [1.0]
Pars Distalis, Hyperplasia, Focal 7 [1.1] 7 [1.3] 7 [1.6] 10 [1.4] 9 [1.3]
Pars Nervosa, Mineralization 1 [3.0]
Thyroid Gland (48) (49) (50) (50) (49)
Inflammation, Chronic, Focal 1 [1.0]
Inflammation, Granulomatous 2 [1.0]
Follicle, Hyperplasia 1 [2.0]
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (47) (48) (50) (47) (49)
Cyst 1 [2.0]
Inflammation, Granulomatous 1 [2.0]
Inflammation, Suppurative 1 [2.0]
Ovary (50) (49) (50) (49) (50)
Angiectasis 1 [3.0] 2 [2.0]
Cyst 19 [2.4] 20 [2.1] 23 [2.0] 16 [1.9] 17 [1.9]
Dysplasia, Focal 1 [1.0] 1 [1.0]
Necrosis, Focal 1 [3.0]
Thrombosis 2 [4.0]
Interstitial Cell, Hyperplasia 1 [3.0]
Uterus (50) (49) (50) (50) (50)
Inflammation, Suppurative 1 [2.0]
Thrombosis 1 [3.0] 1 [4.0]
Ulcer 1 [4.0]
Endometrium, Hyperplasia, Cystic 43 [1.4] 45 [1.4] 43 [1.5] 44 [1.3] 35 [1.3]
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (49) (50) (50) (50)
Hyperplasia 2 [2.5] 11 [1.8] 6 [1.8] 6 [1.8] 13 [2.4]
Lymph Node (2) (1) (7) (5)
Lumbar, Hyperplasia, Lymphoid 1 [2.0]
Pancreatic, Hyperplasia, Lymphoid 1 [3.0]
Renal, Hyperplasia, Lymphoid 1 [4.0]
Lymph Node, Mandibular (49) (49) (48) (47) (44)
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Amyloid Deposition 1 [4.0]
Hyperplasia, Lymphoid 1 [2.0]
Lymph Node, Mesenteric (49) (47) (48) (50) (49)
Atrophy 1 [1.0]
Fibrosis 1 [3.0]
Hematopoietic Cell Proliferation 1 [2.0]
Hyperplasia, Lymphoid 1 [3.0] 1 [2.0]
Infiltration Cellular, Plasma Cell 3 [1.3] 2 [3.0] 1 [2.0] 2 [2.5] 1 [1.0]
Infiltration Cellular, Polymorphonuclear 1 [2.0]
Inflammation, Granulomatous 1 [2.0]
Spleen (50) (49) (50) (49) (50)
Hematopoietic Cell Proliferation 17 [1.8] 14 [1.9] 19 [2.0] 10 [1.8] 19 [1.7]
Lymphoid Follicle, Atrophy 8 [2.9] 4 [2.5] 7 [2.3] 2 [3.5] 4 [2.3]
Lymphoid Follicle, Hyperplasia 8 [1.6] 14 [1.7] 7 [1.0] 12 [1.8] 13 [1.5]
Thymus (47) (48) (49) (48) (50)
Atrophy 26 [2.0] 31 [2.3] 33 [1.7] 24 [2.0] 19 [2.0]
Hyperplasia, Lymphoid 11 [1.6] 7 [1.4] 5 [1.8] 16 [1.6] 14 [1.3]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (49) (50) (49) (49)
Hyperplasia 1 [2.0]
Hyperplasia, Cystic 1 [1.0] 1 [3.0]
Skin (50) (49) (50) (50) (50)
Necrosis 1 [3.0]
Dermis, Fibrosis, Focal 1 [1.0]
Subcutaneous Tissue, Fibrosis 1 [2.0]
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (49) (50) (50) (50)
Fibrosis 19 [1.5] 11 [1.7] 22 [1.9] 21 [1.5] 18 [1.7]
Fracture 1 [4.0]
Joint, Inflammation, Chronic 1 [1.0]
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (48) (50) (50) (50)
Hemorrhage, Focal 1 [2.0]
Hydrocephalus 1 [2.0] 1 [1.0]
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM - CONT
Necrosis, Focal 1 [3.0]
Artery, Meninges, Inflammation, Chronic 1 [2.0]
Hypothalamus, Compression 1 [3.0] 1 [4.0]
Meninges, Inflammation, Acute 1 [4.0]
Peripheral Nerve (1) (2)
Axon, Degeneration 1 [3.0] 2 [2.0]
Spinal Cord (1) (2)
Artery, Inflammation, Chronic 1 [4.0]
Axon, Degeneration 1 [4.0] 1 [3.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (49) (50) (50) (50)
Hemorrhage 1 [1.0] 2 [1.0] 1 [1.0]
Inflammation, Acute, Focal 1 [1.0]
Inflammation, Granulomatous 1 [3.0] 2 [1.0] 3 [1.0] 2 [1.0]
Metaplasia, Osseous 1 [1.0]
Mineralization 1 [4.0]
Alveolar Epithelium, Hyperplasia, Focal 2 [1.5] 3 [1.7] 2 [1.0] 2 [1.0]
Alveolus, Inflammation, Chronic, Focal 1 [1.0]
Nose (50) (49) (50) (50) (50)
Hemorrhage 1 [1.0]
Inflammation, Suppurative 1 [2.0]
Trachea (50) (49) (50) (50) (49)
Glands, Inflammation, Suppurative 1 [1.0]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (1)
Synechia 1 [2.0]
Retrobulbar, Fibrosis 1 [2.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (49) (50) (50) (50)
Hydronephrosis 1 [2.0]
Infarct 4 [1.8] 1 [1.0] 1 [1.0] 5 [1.6] 2 [2.5]
Inflammation, Suppurative 1 [2.0]
Metaplasia, Osseous 3 [1.0] 1 [1.0]
Nephropathy 13 [1.0] 9 [1.0] 16 [1.0] 15 [1.2] 17 [1.0]
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Artery, Inflammation, Chronic 1 [3.0]
Artery, Mineralization 1 [3.0]
Capsule, Inflammation, Granulomatous 1 [1.0]
Glomerulus, Inflammation, Chronic 1 [3.0]
Papilla, Fibrosis, Focal 1 [1.0]
Papilla, Necrosis 1 [1.0]
Pelvis, Inflammation, Granulomatous 1 [2.0]
Renal Tubule, Cyst 1 [1.0] 1 [1.0]
Renal Tubule, Cytoplasmic Alteration 1 [2.0]
Renal Tubule, Degeneration, Focal 1 [2.0]
Renal Tubule, Mineralization 3 [1.0] 4 [1.0] 14 [1.0] 18 [1.0] 6 [1.2]
Renal Tubule, Necrosis 1 [3.0]
Transitional Epithelium, 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 8
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50
Early Deaths
Moribund Sacrifice 1 4 2 6 3
Natural Death 1 3 8 2 7
Survivors
Terminal Sacrifice 47 42 40 42 40
Natural Death 1
Accidently Killed 1
Animals Examined Microscopically 50 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Gallbladder (50) (50) (48) (48) (49)
Epithelium, Cytoplasmic Alteration 1 [4.0]
Intestine Large, Colon (50) (50) (50) (50) (50)
Serosa, Inflammation, Granulomatous 1 [2.0]
Intestine Large, Rectum (50) (50) (50) (50) (50)
Ulcer 1 [4.0]
Intestine Large, Cecum (50) (50) (50) (50) (50)
Edema 1 [3.0]
Serosa, Inflammation, Granulomatous 1 [3.0]
Intestine Small, Duodenum (50) (50) (50) (49) (50)
Epithelium, Hyperplasia, Focal 1 [1.0]
Epithelium, Hypertrophy 1 [2.0]
Epithelium, Metaplasia, Focal, Squamous 1 [1.0]
Epithelium, Necrosis, Focal 2 [1.0]
Peyer's Patch, Inflammation, Granulomatous 1 [1.0]
Intestine Small, Jejunum (50) (50) (50) (50) (50)
Muscularis, Atrophy 1 [3.0]
Muscularis, Inflammation, Chronic 1 [1.0] 1 [2.0]
Peyer's Patch, Hyperplasia, Lymphoid 1 [2.0] 1 [3.0]
Peyer's Patch, Infiltration Cellular, Plasma
Cell 1 [4.0]
Peyer's Patch, Inflammation, Suppurative 1 [1.0]
Serosa, Inflammation, Granulomatous 1 [2.0] 2 [2.0]
Intestine Small, Ileum (50) (50) (50) (50) (50)
Inflammation, Chronic 1 [3.0] 1 [2.0]
Inflammation, Granulomatous 1 [1.0]
Serosa, Inflammation, Granulomatous 1 [1.0] 1 [1.0]
Liver (50) (50) (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 9
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Angiectasis 2 [1.0]
Basophilic Focus 1
Clear Cell Focus 8 9 3 7 2
Eosinophilic Focus 3 4 2 5 1
Hematopoietic Cell Proliferation 1 [1.0] 2 [2.0]
Infiltration Cellular, Mast Cell 1 [1.0] 1 [1.0]
Infiltration Cellular, Lymphocyte 2 [1.0] 1 [1.0] 4 [1.0] 5 [1.0] 4 [1.0]
Inflammation, Granulomatous 9 [1.1] 7 [1.0] 12 [1.0] 12 [1.1] 7 [1.1]
Mixed Cell Focus 9 10 8 9 7
Necrosis, Focal 3 [1.7] 1 [2.0] 4 [1.5] 5 [1.8] 1 [1.0]
Vacuolization Cytoplasmic, Focal 6 [1.2] 11 [1.0] 7 [1.0] 4 [1.0] 4 [1.0]
Bile Duct, Cyst 1 [1.0]
Bile Duct, Cytoplasmic Alteration 1 [1.0]
Bile Duct, Hyperplasia 1 [2.0]
Centrilobular, Degeneration 1 [2.0] 1 [2.0] 1 [1.0]
Periportal, Degeneration 1 [2.0]
Periportal, Fibrosis 1 [1.0]
Mesentery (6) (3) (2) (3) (3)
Inflammation, Chronic 1 [2.0] 1 [1.0] 1 [1.0]
Inflammation, Granulomatous 3 [1.7] 1 [3.0] 1 [1.0] 1 [2.0]
Artery, Inflammation, Chronic 1 [3.0] 1 [3.0]
Fat, Necrosis 1 [2.0] 1 [2.0] 2 [2.0] 1 [2.0]
Oral Mucosa (50) (50) (50) (50) (50)
Inflammation, Chronic Active 6 [2.0] 12 [1.8] 16 [1.9] 21 [1.9] 21 [1.5]
Ulcer 4 [2.3] 9 [1.8] 8 [1.6] 12 [1.4] 10 [1.6]
Pancreas (50) (50) (50) (50) (50)
Inflammation, Chronic Active 1 [1.0]
Salivary Glands (50) (50) (50) (50) (50)
Inflammation, Chronic 1 [1.0]
Duct, Hypertrophy, Focal 1 [2.0]
Stomach, Forestomach (50) (50) (49) (50) (50)
Inflammation, Chronic 1 [2.0]
Inflammation, Suppurative 2 [1.5] 2 [1.5]
Ulcer 1 [2.0] 2 [2.5]
Epithelium, Cyst 2 [2.0]
Epithelium, Hyperkeratosis, Diffuse 1 [1.0] 1 [2.0] 2 [1.0]
Epithelium, Hyperplasia, Diffuse 1 [1.0] 2 [3.0]
Epithelium, Hyperplasia, Focal 1 [1.0] 5 [2.4] 2 [2.5] 2 [2.5]
Stomach, Glandular (50) (50) (50) (50) (50)
Inflammation, Chronic, Focal 1 [1.0]
Ulcer 2 [2.0]
Epithelium, Hyperplasia, Focal 2 [1.5] 1 [2.0]
Epithelium, Inflammation, Acute, Focal 1 [1.0]
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 10
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Glands, Ectasia 1 [1.0] 1 [1.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Blood Vessel (50) (50) (50) (50) (50)
Aorta, Adventitia, Inflammation, Chronic 1 [1.0]
Heart (50) (50) (50) (50) (50)
Artery, Inflammation, Chronic 1 [2.0] 1 [1.0]
Atrium, Thrombosis 1 [4.0]
Coronary Artery, Inflammation, Chronic 1 [1.0] 1 [2.0]
Myocardium, Degeneration 1 [1.0] 2 [1.0] 3 [1.0] 1 [1.0]
Myocardium, Inflammation, Chronic 1 [2.0]
Valve, Inflammation, Chronic 2 [4.0] 1 [3.0] 1 [3.0] 2 [4.0]
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50) (50)
Fibrosis, Focal 1 [1.0] 1 [1.0]
Hyperplasia 1 [1.0]
Hyperplasia, Focal 1 [1.0] 3 [1.0] 1 [1.0] 5 [1.6]
Hypertrophy 1 [1.0]
Hypertrophy, Focal 25 [1.5] 25 [1.3] 17 [1.1] 28 [1.1] 22 [1.0]
Inflammation, Granulomatous 1 [1.0]
Mineralization, Focal 1 [1.0]
Vacuolization Cytoplasmic, Focal 1 [1.0] 1 [1.0]
Subcapsular, Hyperplasia 36 [1.0] 42 [1.2] 40 [1.1] 47 [1.0] 39 [1.1]
Subcapsular, Hyperplasia, Focal 1 [1.0]
Adrenal Medulla (49) (50) (50) (50) (50)
Hyperplasia, Focal 1 [3.0] 1 [1.0]
Islets, Pancreatic (50) (50) (50) (50) (50)
Hyperplasia 15 [1.1] 18 [1.3] 28 [1.4] 30 [1.1] 9 [1.0]
Parathyroid Gland (43) (43) (39) (44) (37)
Cyst 2 [1.5]
Hyperplasia, Focal 1 [1.0]
Pituitary Gland (50) (48) (49) (47) (50)
Cyst 1 [1.0] 1 [1.0] 1 [1.0] 1 [1.0]
Pars Distalis, Hyperplasia, Focal 1 [1.0] 3 [1.0]
____________________________________________________________________________________________________________________________________
GENERAL BODY 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 11
NTP Experiment-Test: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (50) (50) (50) (50) (50)
Granuloma Sperm 1 [2.0] 1 [3.0]
Inflammation, Chronic Active 1 [1.0]
Inflammation, Granulomatous 1 [2.0]
Preputial Gland (50) (50) (50) (50) (50)
Atrophy 1 [4.0]
Cyst 17 [2.8] 14 [2.8] 19 [2.8] 18 [2.8] 12 [3.0]
Inflammation, Granulomatous 3 [2.0] 1 [3.0] 2 [2.0] 1 [1.0]
Inflammation, Suppurative 2 [2.5] 3 [1.7] 2 [3.0] 1 [2.0] 4 [2.5]
Prostate (50) (50) (50) (50) (50)
Inflammation, Chronic Active 1 [2.0] 1 [3.0]
Artery, Inflammation, Chronic 1 [2.0]
Seminal Vesicle (50) (50) (50) (50) (50)
Fibrosis 1 [3.0] 3 [1.3]
Testes (50) (50) (50) (50) (50)
Germinal Epithelium, Degeneration 4 [1.0] 2 [1.5] 4 [1.0] 4 [1.3]
Germinal Epithelium, Mineralization 1 [1.0] 1 [1.0]
Tunic, Mineralization 1 [1.0] 1 [1.0]
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (50) (50) (50)
Hyperplasia 9 [1.9] 19 [1.5] 18 [2.1] 14 [1.6] 14 [1.8]
Inflammation, Focal, Suppurative 1 [1.0]
Lymph Node, Mandibular (48) (45) (47) (47) (49)
Infiltration Cellular, Mast Cell 1 [3.0]
Lymph Node, Mesenteric (48) (47) (49) (48) (50)
Congestion 1 [3.0]
Hematopoietic Cell Proliferation 1 [2.0]
Hyperplasia, Lymphoid 1 [3.0]
Infiltration Cellular, Plasma Cell 1 [3.0] 1 [4.0]
Infiltration Cellular, Histiocyte 1 [2.0] 1 [4.0]
Inflammation, Granulomatous 1 [2.0] 1 [2.0]
Spleen (50) (50) (49) (50) (50)
Hematopoietic Cell Proliferation 17 [1.3] 13 [1.8] 18 [1.9] 13 [2.0] 11 [1.7]
Infiltration Cellular, Mast Cell 1 [2.0] 1 [1.0]
Lymphoid Follicle, Atrophy 3 [2.7] 4 [2.8] 5 [1.8] 3 [3.3] 6 [2.2]
Lymphoid Follicle, Hyperplasia 6 [1.7] 8 [1.8] 3 [1.3] 3 [2.3] 5 [1.2]
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Thymus (50) (49) (48) (48) (46)
Atrophy 41 [2.2] 43 [2.0] 39 [2.3] 32 [2.2] 41 [1.9]
Ectopic Parathyroid Gland 1 [1.0]
Hyperplasia, Lymphoid 1 [2.0]
Inflammation, Suppurative 1 [4.0]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (50) (50) (50) (50) (50)
Cyst Epithelial Inclusion 1
Dermis, Inflammation, Chronic, Focal 1 [1.0]
Epidermis, Hyperplasia, Focal 2 [1.0] 1 [3.0]
Subcutaneous Tissue, Inflammation,
Granulomatous 1 [3.0] 1 [3.0]
Subcutaneous Tissue, Inflammation,
Suppurative 1 [3.0]
Subcutaneous Tissue, Necrosis 1 [1.0]
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50) (50)
Fibrosis 1 [2.0] 3 [1.3] 1 [1.0]
Inflammation, Granulomatous 1 [2.0]
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50) (50)
Cyst Epithelial Inclusion 1
Peripheral Nerve (1)
Axon, Degeneration 1 [3.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50) (50)
Hemorrhage 6 [1.3] 2 [1.5]
Inflammation, Chronic, Focal 1 [1.0]
Inflammation, Granulomatous 1 [1.0] 1 [1.0] 1 [1.0]
Alveolar Epithelium, Hyperplasia 1 [3.0]
Alveolar Epithelium, Hyperplasia, Focal 2 [1.5] 1 [1.0] 1 [2.0] 4 [1.5] 2 [3.5]
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: 56348-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC WITH AVERAGE SEVERITY GRADES[b] Date: 07/05/01
Route: DOSED FEED CITRAL Time: 14:03:02
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE UNTREAT VEHICLE 500 PPM 1000 PPM 2000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Alveolus, Infiltration Cellular, Histiocyte 1 [3.0]
Bronchiole, Inflammation, Suppurative 1 [1.0]
Serosa, Fibrosis 2 [1.0] 1 [2.0]
Serosa, Fibrosis, Focal 1 [1.0]
Serosa, Inflammation, Chronic 1 [1.0]
Nose (50) (50) (50) (50) (50)
Infiltration Cellular, Mast Cell 1 [2.0]
Inflammation, Suppurative 1 [2.0] 1 [1.0]
Sinus, Inflammation, Suppurative 1 [2.0]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (1)
Anterior Chamber, Infiltration Cellular,
Histiocyte 1 [2.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50) (50) (50) (50)
Infarct 2 [1.0] 8 [1.1] 5 [1.8] 6 [1.3] 3 [2.0]
Infiltration Cellular, Mast Cell 1 [3.0]
Inflammation, Granulomatous 1 [3.0] 1 [1.0]
Inflammation, Suppurative 1 [1.0]
Metaplasia, Osseous 2 [1.0] 3 [1.0] 3 [1.0] 1 [1.0]
Nephropathy 45 [1.1] 46 [1.0] 36 [1.1] 46 [1.0] 38 [1.1]
Artery, Inflammation, Chronic 1 [2.0]
Artery, Inflammation, Suppurative 1 [3.0]
Capsule, Inflammation, Chronic 1 [1.0]
Papilla, Hemorrhage 1 [2.0]
Pelvis, Hemorrhage 1 [2.0]
Renal Tubule, Cyst 8 [1.5] 4 [2.0] 6 [1.8] 6 [1.3] 4 [1.0]
Renal Tubule, Cytoplasmic Alteration 1 [3.0]
Renal Tubule, Hyperplasia 2 [1.0] 1 [1.0] 2 [2.0] 2 [1.0]
Renal Tubule, Mineralization 45 [1.0] 48 [1.0] 43 [1.0] 50 [1.0] 33 [1.0]
Urinary Bladder (50) (50) (49) (50) (50)
Inflammation, Chronic 1 [1.0]
Transitional Epithelium, Cytoplasmic
Alteration 1 [2.0] 1 [2.0]
Transitional Epithelium, Hyperplasia 1 [2.0] 1 [1.0]
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
------------------------------------------------------------
---------- END OF REPORT ----------
------------------------------------------------------------