TDMS Study 56348-03 Pathology Tables
NTP Experiment-Test: 56348-03 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: 15:32:57
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50
Early Deaths
Moribund Sacrifice 12 10 11 11 12
Natural Death 3 3 3 2
Survivors
Terminal Sacrifice 34 40 36 36 36
Natural Death 1
Animals Examined Microscopically 50 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Colon (50) (50) (50) (50) (50)
Inflammation 1 [1.0]
Parasite Metazoan 2 2 2
Ulcer 1 [2.0]
Intestine Large, Rectum (50) (50) (50) (50) (50)
Parasite Metazoan 7 4 1 6 3
Intestine Large, Cecum (50) (50) (50) (50) (49)
Inflammation 1 [1.0]
Intestine Small, Duodenum (50) (50) (50) (50) (50)
Inflammation 1 [1.0]
Parasite Metazoan 1
Intestine Small, Jejunum (50) (50) (50) (49) (50)
Dysplasia 1 [4.0]
Inflammation 1 [1.0]
Polyp Inflammatory 1 [4.0]
Ulcer 1 [4.0]
Lymphatic, Cyst 1 [4.0]
Intestine Small, Ileum (50) (50) (50) (50) (50)
Inflammation 1 [1.0]
Liver (50) (50) (50) (50) (50)
Angiectasis 3 [1.3] 1 [1.0] 1 [1.0] 1 [1.0]
Basophilic Focus 42 48 44 45 42
Clear Cell Focus 1
Degeneration, Cystic 1 [1.0] 2 [1.0]
Eosinophilic Focus 8 8 7 3 9
Fatty Change 1 [4.0] 4 [1.5]
Fibrosis 1 [1.0]
Hematopoietic Cell Proliferation 1 [1.0] 3 [1.0]
Hepatodiaphragmatic Nodule 10 8 8 4 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 2
NTP Experiment-Test: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Inflammation 40 [1.9] 44 [2.0] 44 [1.7] 41 [1.8] 43 [1.9]
Mixed Cell Focus 16 18 11 16 15
Necrosis 2 [1.5] 1 [1.0]
Vacuolization Cytoplasmic 5 [1.0] 12 [1.0] 7 [1.0] 4 [1.5] 6 [1.0]
Bile Duct, Hyperplasia 25 [1.2] 15 [1.2] 17 [1.4] 13 [1.3] 13 [1.4]
Centrilobular, Degeneration 5 [2.2] 6 [1.2] 9 [1.8] 7 [1.3] 7 [1.4]
Mesentery (10) (5) (1) (5) (7)
Hemorrhage 1 [4.0]
Inflammation 2 [1.5]
Thrombosis 1 [1.0]
Fat, Necrosis 8 [2.5] 3 [2.3] 1 [2.0] 4 [2.3] 5 [2.0]
Pancreas (50) (50) (50) (50) (50)
Atrophy 8 [1.1] 12 [1.1] 20 [1.1] 8 [1.1] 10 [1.2]
Cyst 2 [1.0]
Cytoplasmic Alteration 2 [1.0] 1 [1.0] 1 [1.0] 2 [1.0]
Hyperplasia 1 [2.0] 2 [1.0] 2 [1.5]
Inflammation 1 [1.0] 1 [1.0]
Metaplasia, Hepatocyte 1 [1.0]
Salivary Glands (50) (50) (50) (50) (50)
Atrophy 2 [1.0] 1 [1.0]
Inflammation 2 [1.0]
Stomach, Forestomach (50) (49) (50) (50) (50)
Edema 1 [2.0]
Hyperplasia 1 [1.0]
Inflammation 1 [2.0] 1 [2.0]
Ulcer 2 [2.0] 2 [1.0] 1 [1.0]
Epithelium, Hyperplasia 6 [1.5] 1 [2.0] 4 [2.0] 3 [1.3] 1 [2.0]
Stomach, Glandular (50) (50) (50) (50) (50)
Erosion 2 [1.0] 1 [1.0] 1 [1.0] 4 [1.0] 2 [1.0]
Fibrosis 1 [1.0]
Inflammation 1 [1.0]
Mineralization 1 [1.0] 1 [1.0]
Ulcer 1 [1.0]
Epithelium, Mineralization 1 [1.0]
Tooth (1) (2) (2)
Inflammation 2 [2.5] 1 [4.0]
Malformation 1
Peridontal Tissue, Inflammation 1 [2.0] 1 [2.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Blood Vessel (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 3
NTP Experiment-Test: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM - CONT
Inflammation 1 [1.0]
Heart (50) (50) (50) (50) (50)
Cardiomyopathy 41 [1.1] 48 [1.1] 40 [1.1] 42 [1.1] 39 [1.1]
Fibrosis 1 [1.0]
Hemorrhage 1 [1.0]
Necrosis 1 [2.0]
Thrombosis 1 [1.0] 1 [1.0]
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50) (50)
Angiectasis 1 [1.0] 1 [2.0] 3 [1.0] 10 [1.0]
Atrophy 1 [3.0]
Atypia Cellular 1 [1.0]
Degeneration, Cystic 1 [2.0]
Hyperplasia 14 [1.1] 16 [1.2] 13 [1.2] 12 [1.3] 8 [1.1]
Hypertrophy 10 [1.5] 4 [1.5] 3 [1.3] 3 [1.7] 4 [1.3]
Thrombosis 1 [2.0]
Vacuolization Cytoplasmic 1 [2.0] 2 [1.0] 6 [1.8] 2 [1.5]
Adrenal Medulla (49) (50) (50) (50) (50)
Hyperplasia 8 [1.3] 3 [1.3] 4 [1.0] 3 [2.0] 3 [1.7]
Infiltration Cellular, Lymphocyte 1 [1.0]
Islets, Pancreatic (50) (50) (50) (50) (49)
Hyperplasia 1 [3.0]
Parathyroid Gland (43) (43) (40) (43) (47)
Hyperplasia 1 [2.0]
Pituitary Gland (50) (50) (50) (50) (49)
Cyst 1 [3.0] 2 [3.5] 3 [1.3] 3 [1.3]
Hyperplasia 1 [4.0]
Pars Distalis, Cyst 1 [2.0] 1 [2.0] 1 [1.0]
Pars Distalis, Hyperplasia 27 [2.3] 29 [2.1] 31 [1.9] 23 [1.8] 27 [2.0]
Pars Intermedia, Hyperplasia 1 [2.0] 1 [1.0]
Thyroid Gland (50) (50) (50) (50) (50)
C-Cell, Hyperplasia 45 [1.4] 45 [1.4] 39 [1.2] 43 [1.5] 36 [1.2]
Follicular Cell, Hyperplasia 1 [1.0] 2 [1.5]
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (49) (49) (49) (50) (49)
Hyperplasia 7 [2.3] 17 [2.4] 8 [1.4] 15 [2.4] 4 [2.5]
Inflammation 13 [1.3] 22 [1.3] 20 [1.1] 19 [1.1] 24 [1.2]
Metaplasia 1 [1.0]
Bilateral, Cyst 1 [2.0]
Duct, Cyst 5 [1.6] 5 [1.8] 3 [2.0] 6 [1.5] 4 [2.0]
Ovary (50) (50) (50) (50) (50)
Atrophy 2 [3.0] 1 [4.0]
Cyst 3 [3.3] 11 [2.0] 6 [2.5] 4 [2.5] 5 [2.4]
Infiltration Cellular, Lymphocyte 1 [2.0] 2 [2.5]
Uterus (50) (50) (50) (50) (50)
Fibrosis 1 [4.0]
Hemorrhage 1 [2.0] 1 [4.0]
Hyperplasia 1 [4.0]
Hyperplasia, Cystic 1 [2.0]
Inflammation 1 [3.0]
Cervix, Prolapse 1
Endometrium, Hyperplasia, Cystic 9 [2.0] 12 [1.9] 15 [1.6] 9 [2.0] 14 [1.4]
Vagina (2) (1) (2)
Dilatation 1 [4.0]
Hyperplasia 1 [3.0]
Hypertrophy 1 [2.0]
Inflammation, Acute 1 [3.0]
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (50) (50) (50)
Angiectasis 1 [3.0]
Atrophy 1 [1.0] 1 [1.0] 2 [1.0] 1 [1.0]
Hyperplasia 11 [2.5] 9 [2.7] 12 [2.1] 10 [2.7] 10 [2.4]
Myelofibrosis 1 [3.0] 1 [2.0] 1 [2.0]
Necrosis 1 [3.0]
Lymph Node (7) (4) (7) (10) (5)
Lumbar, Hyperplasia, Histiocytic 1 [1.0]
Mediastinal, Congestion 1 [2.0]
Mediastinal, Hyperplasia, Plasma Cell 1 [3.0]
Lymph Node, Mandibular (50) (50) (50) (50) (50)
Ectasia 10 [1.1] 3 [1.0] 5 [1.0] 7 [1.6]
Hyperplasia, Plasma Cell 6 [1.8] 17 [1.9] 17 [2.0] 7 [2.1] 17 [2.0]
Necrosis 1 [1.0]
Lymph Node, Mesenteric (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 5
NTP Experiment-Test: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Atrophy 1 [3.0]
Ectasia 1 [2.0]
Hyperplasia, Lymphoid 1 [2.0]
Spleen (50) (50) (50) (50) (50)
Accessory Spleen 1
Ectopic Tissue 1 [2.0]
Fibrosis 1 [2.0] 1 [2.0]
Granuloma 1 [3.0]
Hematopoietic Cell Proliferation 11 [1.8] 11 [2.3] 8 [1.6] 5 [2.8] 5 [1.6]
Hemorrhage 1 [4.0]
Hyperplasia, Histiocytic 1 [2.0]
Hyperplasia, Adenomatous 1 [4.0]
Infarct 1 [3.0]
Infiltration Cellular, Lipocyte 1 [1.0]
Necrosis 1 [4.0]
Pigmentation 1 [2.0] 1 [2.0] 3 [2.3]
Red Pulp, Depletion Cellular 1 [4.0]
Thymus (49) (47) (49) (48) (49)
Atrophy 45 [3.3] 46 [3.5] 45 [3.3] 44 [3.6] 46 [3.4]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (50) (50) (50) (50)
Galactocele 3 [2.0] 1 [3.0] 2 [4.0] 3 [2.7]
Hyperplasia 1 [3.0] 4 [1.3] 1 [2.0]
Hyperplasia, Focal 4 [1.3] 5 [1.2] 10 [1.2] 6 [2.5] 3 [1.3]
Hyperplasia, Lobular 1 [1.0]
Skin (50) (50) (50) (50) (50)
Cyst Epithelial Inclusion 1
Fibrosis 1 [4.0]
Hyperkeratosis 1 [1.0]
Hyperplasia 1 [2.0]
Inflammation 1 [1.0]
Dermis, Fibrosis 1 [4.0]
Subcutaneous Tissue, Inflammation 1 [2.0]
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50) (50)
Osteopetrosis 3 [2.3] 3 [2.3] 12 [2.0] 5 [2.8] 8 [3.1]
____________________________________________________________________________________________________________________________________
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50) (50)
Hemorrhage 3 [2.3] 2 [2.5] 4 [2.3] 4 [2.3]
Necrosis 1 [2.0] 4 [2.0]
Spinal Cord (1)
Hemorrhage 1 [3.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50) (50)
Fibrosis 1 [1.0]
Hemorrhage 2 [1.0] 1 [1.0] 1 [1.0] 1 [1.0]
Hyperplasia, Lymphoid 1 [2.0]
Inflammation 9 [1.2] 7 [1.4] 17 [1.0] 9 [1.0] 9 [1.0]
Alveolar Epithelium, Hyperplasia 9 [1.6] 10 [1.3] 9 [1.2] 10 [1.7] 11 [1.8]
Nose (50) (50) (50) (50) (50)
Foreign Body 3 1 4 1 3
Inflammation 4 [1.3] 5 [1.0] 5 [1.2] 2 [2.0] 3 [1.3]
Trachea (50) (50) (50) (50) (50)
Inflammation 1 [1.0] 1 [1.0] 3 [1.0] 1 [1.0] 1 [1.0]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (2) (3) (1) (2)
Cataract 2 [3.5] 2 [3.0] 1 [3.0] 1 [2.0]
Cornea, Inflammation 1 [4.0]
Retina, Degeneration 2 [4.0] 2 [2.0] 1 [3.0] 1 [3.0]
Harderian Gland (1)
Atrophy 1 [4.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50) (50) (50) (50)
Accumulation, Hyaline Droplet 1 [3.0] 1 [1.0]
Cyst 1 [3.0] 1 [2.0]
Hydronephrosis 2 [1.5] 1 [1.0]
Inflammation 1 [1.0] 1 [2.0] 1 [3.0]
Mineralization 41 [1.0] 43 [1.0] 43 [1.0] 38 [1.0] 41 [1.0]
Necrosis 2 [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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Nephropathy 41 [1.0] 44 [1.1] 45 [1.0] 48 [1.0] 44 [1.0]
Pigmentation 2 [2.0] 1 [1.0] 4 [1.3] 1 [2.0]
Renal Tubule, Hyperplasia 1 [1.0] 1 [1.0]
Transitional Epithelium, Hyperplasia 1 [1.0]
Urinary Bladder (50) (50) (50) (50) (50)
Calculus Gross Observation 1
Hemorrhage 1 [3.0] 1 [2.0]
Inflammation 1 [2.0]
Ulcer 1 [2.0]
Transitional Epithelium, Hyperplasia 1 [2.0] 1 [4.0]
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50
Early Deaths
Moribund Sacrifice 18 22 15 11 10
Natural Death 2 6 3 4 6
Survivors
Terminal Sacrifice 30 22 32 35 34
Animals Examined Microscopically 50 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Colon (50) (50) (50) (50) (50)
Dysplasia 1 [4.0]
Inflammation 1 [4.0]
Parasite Metazoan 4 4 2
Ulcer 1 [4.0]
Artery, Inflammation 1 [3.0]
Lymphoid Tissue, Hyperplasia 1 [1.0]
Intestine Large, Rectum (50) (50) (50) (50) (50)
Inflammation 1 [1.0] 1 [3.0]
Parasite Metazoan 7 3 7 8 8
Intestine Large, Cecum (50) (50) (50) (49) (50)
Edema 1 [2.0]
Inflammation 2 [3.5]
Parasite Metazoan 1
Ulcer 1 [1.0] 2 [3.5]
Intestine Small, Duodenum (50) (50) (50) (50) (50)
Inflammation 1 [1.0]
Intestine Small, Jejunum (50) (50) (50) (50) (50)
Inflammation 1 [3.0] 3 [2.0] 2 [2.5] 1 [2.0] 1 [2.0]
Inflammation, Granulomatous 1 [4.0]
Intestine Small, Ileum (50) (50) (49) (50) (50)
Erosion 1 [4.0]
Inflammation 2 [1.5] 1 [1.0] 1 [4.0] 2 [2.0]
Parasite Metazoan 1 1
Liver (50) (50) (50) (50) (50)
Angiectasis 5 [1.0] 1 [1.0] 4 [1.0] 1 [1.0]
Basophilic Focus 33 24 33 33 29
Clear Cell Focus 14 7 11 16 9
Degeneration, Cystic 3 [1.0] 2 [1.0] 1 [1.0] 1 [1.0] 5 [1.0]
Developmental Malformation 1
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Eosinophilic Focus 6 3 5 3 6
Fatty Change 2 [2.0] 4 [1.5] 1 [3.0]
Hematopoietic Cell Proliferation 3 [1.3] 1 [2.0] 1 [1.0] 1 [1.0]
Hepatodiaphragmatic Nodule 6 3 7 4 7
Inflammation 21 [1.0] 22 [1.0] 28 [1.1] 27 [1.0] 28 [1.1]
Mixed Cell Focus 5 1 8 5 7
Necrosis 1 [1.0] 1 [1.0]
Vacuolization Cytoplasmic 7 [1.0] 6 [1.0] 7 [1.0] 8 [1.3] 3 [1.0]
Bile Duct, Fibrosis 1 [1.0]
Bile Duct, Hyperplasia 48 [1.8] 45 [1.7] 50 [1.8] 45 [1.7] 47 [1.7]
Centrilobular, Degeneration 22 [2.0] 19 [1.9] 14 [2.3] 15 [1.9] 16 [2.1]
Mesentery (8) (13) (11) (11) (5)
Inflammation 1 [3.0] 1 [3.0]
Fat, Necrosis 7 [2.7] 11 [2.9] 7 [3.0] 9 [2.4] 3 [2.3]
Oral Mucosa (1) (2)
Inflammation, Chronic Active 1 [3.0]
Pancreas (50) (50) (50) (50) (50)
Atrophy 22 [1.5] 18 [1.2] 17 [1.1] 14 [1.4] 16 [1.3]
Cytoplasmic Alteration 1 [1.0] 2 [1.0] 3 [1.0] 2 [1.0] 1 [1.0]
Hyperplasia 3 [1.3] 2 [3.0] 7 [2.0] 2 [2.0]
Inflammation 2 [1.0] 1 [1.0]
Metaplasia, Hepatocyte 2 [1.0]
Thrombosis 1 [2.0]
Artery, Inflammation 1 [2.0] 3 [2.7] 2 [3.5]
Salivary Glands (50) (50) (50) (50) (50)
Atrophy 1 [1.0] 1 [3.0] 2 [1.5] 1 [2.0]
Cytoplasmic Alteration 1 [1.0]
Stomach, Forestomach (50) (50) (50) (50) (50)
Edema 1 [2.0] 1 [3.0] 1 [3.0] 2 [1.5]
Inflammation 1 [1.0] 3 [1.7] 1 [3.0] 2 [2.5]
Ulcer 1 [1.0] 3 [1.3] 2 [2.5] 3 [1.7] 3 [2.7]
Epithelium, Hyperplasia 1 [2.0] 6 [1.8] 7 [1.7] 8 [1.8] 3 [2.0]
Epithelium, Hyperplasia, Basal Cell 1 [2.0] 1 [1.0] 1 [2.0]
Stomach, Glandular (50) (50) (50) (50) (50)
Atrophy 1 [1.0]
Erosion 2 [1.0] 7 [1.0] 3 [1.0] 2 [1.0] 2 [1.0]
Inflammation 1 [1.0] 1 [1.0] 1 [3.0]
Necrosis 1 [3.0]
Thrombosis 1 [2.0]
Ulcer 3 [1.0] 4 [1.5] 2 [1.5] 5 [1.0] 1 [1.0]
Epithelium, Ulcer 1 [1.0]
Tongue (1) (1) (1)
Inflammation 1 [4.0]
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Tooth (1) (1) (1)
Degeneration 1 [2.0]
Malformation 1 [4.0]
Peridontal Tissue, Inflammation 1 [1.0] 1 [2.0]
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Blood Vessel (50) (50) (50) (50) (50)
Inflammation 2 [1.5]
Jugular Vein, Thrombosis 1 [2.0]
Heart (50) (50) (50) (50) (50)
Cardiomyopathy 39 [1.3] 43 [1.3] 45 [1.5] 50 [1.5] 47 [1.6]
Fibrosis 1 [2.0]
Inflammation 2 [1.5] 1 [1.0]
Thrombosis 6 [1.8] 2 [2.0] 2 [1.5] 2 [2.5]
Valve, Inflammation 1 [1.0]
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50) (50)
Angiectasis 1 [1.0] 1 [1.0]
Atrophy 1 [3.0]
Hematopoietic Cell Proliferation 2 [1.0]
Hyperplasia 12 [1.0] 13 [1.2] 20 [1.3] 11 [1.2] 14 [1.1]
Hypertrophy 1 [1.0]
Necrosis 3 [1.7] 1 [1.0] 1 [3.0] 2 [3.0]
Thrombosis 1 [1.0]
Vacuolization Cytoplasmic 4 [2.0] 7 [1.1] 1 [3.0] 2 [1.0] 3 [1.0]
Adrenal Medulla (50) (50) (50) (50) (50)
Hyperplasia 12 [2.0] 16 [1.4] 23 [2.0] 14 [2.0] 15 [1.6]
Necrosis 1 [4.0]
Thrombosis 1 [2.0]
Islets, Pancreatic (49) (50) (50) (50) (50)
Hyperplasia 1 [2.0]
Parathyroid Gland (48) (45) (47) (45) (45)
Hyperplasia 1 [1.0] 2 [1.0] 1 [1.0]
Pituitary Gland (50) (50) (50) (50) (49)
Atrophy 1 [3.0]
Cyst 5 [1.4] 4 [1.0] 5 [1.2] 4 [2.5] 2 [1.0]
Necrosis 1 [1.0]
Pars Distalis, Cyst 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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Pars Distalis, Hemorrhage 1 [4.0]
Pars Distalis, Hyperplasia 15 [1.7] 22 [1.9] 24 [1.7] 19 [1.9] 18 [1.7]
Pars Intermedia, Hyperplasia 1 [1.0] 1 [2.0]
Pars Nervosa, Hyperplasia 1 [1.0]
Rathke's Cleft, Hyperplasia 1 [4.0]
Thyroid Gland (50) (50) (50) (50) (50)
Inflammation 1 [1.0]
C-Cell, Hyperplasia 32 [1.4] 38 [1.3] 41 [1.4] 41 [1.4] 34 [1.5]
Follicular Cell, Hyperplasia 1 [1.0] 2 [2.0] 1 [1.0] 4 [1.0] 3 [1.7]
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Coagulating Gland (1) (1) (1)
Inflammation 1 [2.0]
Epididymis (50) (50) (50) (50) (50)
Atrophy 1 [4.0]
Inflammation 1 [1.0] 3 [1.0] 1 [1.0] 2 [1.0]
Preputial Gland (50) (50) (49) (50) (50)
Hyperplasia 2 [2.0] 2 [2.0] 1 [2.0] 2 [3.0]
Inflammation 47 [1.9] 48 [1.9] 47 [1.9] 49 [2.0] 47 [1.9]
Duct, Ectasia 1 [2.0] 2 [3.0] 1 [2.0]
Prostate (50) (50) (50) (50) (50)
Cyst 4 [2.0] 1 [2.0] 8 [2.4] 1 [1.0] 2 [2.0]
Hyperplasia 2 [2.0] 3 [1.7] 3 [2.0]
Inflammation 1 [1.0] 2 [1.5]
Inflammation, Chronic Active 29 [1.5] 33 [1.5] 30 [1.3] 28 [1.3] 22 [1.6]
Dorsal, Inflammation, Chronic Active 1 [1.0] 1 [1.0]
Ventral, Hyperplasia 1 [3.0]
Seminal Vesicle (50) (50) (50) (50) (50)
Atrophy 1 [2.0]
Hyperplasia 1 [1.0]
Inflammation 1 [1.0]
Testes (50) (50) (50) (50) (50)
Angiectasis 1 [4.0]
Atrophy 2 [4.0] 2 [4.0] 3 [3.3] 1 [4.0]
Hyperplasia 1 [1.0]
Interstitial Cell, Hyperplasia 4 [2.3] 7 [2.0] 4 [1.0] 9 [1.0] 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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (50) (50) (50)
Atrophy 3 [1.7] 1 [1.0] 2 [2.0]
Hemorrhage 1 [2.0]
Hyperplasia 14 [2.6] 16 [2.9] 20 [2.3] 14 [2.5] 13 [2.4]
Myelofibrosis 2 [2.5] 2 [1.0] 1 [4.0] 1 [2.0]
Necrosis 1 [4.0]
Lymph Node (15) (20) (10) (10) (12)
Deep Cervical, Hyperplasia, Plasma Cell 1 [2.0]
Inguinal, Ectasia 1 [4.0]
Inguinal, Necrosis 1 [4.0]
Mediastinal, Ectasia 1 [2.0] 1 [4.0]
Mediastinal, Necrosis 2 [4.0]
Renal, Necrosis 1 [4.0]
Lymph Node, Mandibular (50) (49) (50) (50) (50)
Atrophy 1 [3.0]
Ectasia 4 [1.0] 3 [1.3] 2 [1.5] 9 [1.3] 1 [1.0]
Hyperplasia 1 [2.0]
Hyperplasia, Plasma Cell 17 [2.0] 13 [2.2] 13 [1.9] 18 [2.1] 20 [2.1]
Inflammation 1 [2.0]
Necrosis 1 [1.0] 1 [4.0]
Lymph Node, Mesenteric (50) (50) (50) (50) (50)
Atrophy 1 [4.0] 1 [2.0]
Ectasia 3 [1.3] 1 [3.0] 5 [3.0] 1 [1.0]
Inflammation 1 [2.0]
Inflammation, Granulomatous 1 [4.0]
Necrosis 1 [4.0] 1 [1.0]
Spleen (50) (50) (50) (50) (49)
Accessory Spleen 1 1
Angiectasis 1 [2.0]
Congestion 1 [1.0] 1 [2.0]
Fibrosis 2 [1.5] 2 [1.0] 2 [2.0] 2 [1.0] 1 [4.0]
Hematopoietic Cell Proliferation 3 [1.3] 8 [3.0] 2 [2.5] 4 [3.3] 5 [1.6]
Hemorrhage 1 [3.0]
Infarct 2 [1.5] 2 [2.0] 1 [4.0] 2 [2.5]
Necrosis 2 [1.5]
Pigmentation 2 [2.5] 1 [2.0] 1 [2.0]
Lymphoid Follicle, Atrophy 2 [2.5] 1 [4.0] 1 [2.0]
Red Pulp, Depletion Cellular 1 [1.0] 2 [3.0]
Thymus (50) (47) (49) (47) (49)
Atrophy 45 [3.4] 38 [3.6] 47 [3.5] 44 [3.6] 45 [3.5]
Inflammation 1 [4.0]
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: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Epithelial Cell, Hyperplasia 1 [3.0]
Vein, Inflammation 1 [3.0]
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (50) (50) (49) (50)
Hyperplasia 3 [1.3] 7 [1.7] 5 [1.2] 9 [1.2] 6 [1.5]
Skin (50) (50) (50) (50) (50)
Hemorrhage 1 [2.0]
Hyperkeratosis 4 [2.0] 3 [2.7]
Hyperplasia 1 [3.0] 1 [2.0] 1 [2.0]
Inflammation 3 [3.0] 1 [4.0] 4 [2.0]
Inflammation, Chronic Active 1 [3.0]
Parakeratosis 1 [4.0]
Ulcer 2 [1.0]
Dermis, Fibrosis 1 [4.0]
Dermis, Necrosis 1 [2.0]
Epidermis, Hyperplasia 2 [3.0] 1 [2.0]
Epidermis, Inflammation, Acute 1 [2.0] 1 [2.0]
Subcutaneous Tissue, Fibrosis 1 [2.0] 1 [4.0]
Subcutaneous Tissue, Mineralization 1 [2.0]
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50) (50)
Necrosis 1 [1.0]
Osteopetrosis 1 [2.0] 1 [3.0]
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50) (50)
Hemorrhage 5 [1.2] 9 [1.6] 1 [1.0] 2 [2.5] 2 [3.0]
Necrosis 1 [2.0] 1 [1.0] 1 [2.0]
Spinal Cord (2)
Hemorrhage 2 [3.0]
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (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 14
NTP Experiment-Test: 56348-03 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: 15:32:57
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE UNTREAT VEHICLE 1000 PPM 2000 PPM 4000 PPM
CONTROL CONTROL
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Embolus, Cartilagenous 1 [4.0]
Foreign Body 1
Hemorrhage 6 [1.0] 2 [1.0] 1 [1.0] 2 [1.0]
Inflammation 12 [1.3] 12 [1.2] 6 [1.5] 8 [1.0] 5 [1.2]
Necrosis 1 [2.0]
Thrombosis 1 [1.0] 3 [1.0] 1 [1.0]
Alveolar Epithelium, Hyperplasia 7 [2.0] 6 [2.2] 10 [1.6] 10 [1.7] 11 [2.2]
Artery, Inflammation 1 [2.0]
Bronchiole, Hyperplasia 1 [1.0]
Bronchus, Hyperplasia 1 [1.0]
Mediastinum, Inflammation 1 [4.0]
Nose (50) (50) (50) (50) (50)
Dysplasia 1 [1.0]
Foreign Body 7 7 6 9 7
Inflammation 13 [1.1] 11 [1.3] 9 [1.1] 14 [1.4] 8 [1.5]
Trachea (50) (50) (50) (50) (50)
Inflammation 1 [1.0] 1 [1.0]
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (1) (3) (3) (2) (3)
Cataract 1 [2.0] 3 [2.7] 2 [2.5] 1 [2.0] 3 [3.3]
Retina, Degeneration 1 [3.0] 3 [3.3] 2 [3.0] 1 [2.0] 3 [4.0]
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50) (50) (50) (50)
Accumulation, Hyaline Droplet 2 [1.5] 2 [1.5] 3 [1.0]
Cyst 4 [1.5]
Infarct 3 [2.0] 1 [2.0]
Mineralization 45 [1.0] 42 [1.0] 45 [1.0] 48 [1.4] 50 [2.4]
Necrosis 1 [1.0]
Nephropathy 49 [1.5] 50 [1.3] 50 [1.5] 49 [1.5] 50 [1.6]
Pigmentation 3 [1.7] 2 [2.5] 2 [1.5] 6 [1.7]
Thrombosis 2 [1.5]
Renal Tubule, Hyperplasia 2 [2.0] 1 [1.0] 2 [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 15
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