TDMS Study 05150-01 Pathology Tables
INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)
METHLYPHENIDATE HYDROCHLORIDE
NTP Experiment-Test: 05150-01 Report: PEIRPT03
Study Type: CHRONIC Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
Facility: TSI Mason Research
Chemical CAS #: 298-59-9
Lock Date: 02/06/92
Cage Range: All
Reasons For Removal: All
Removal Date Range: All
Treatment Groups: Include All
a Number of animals examined microscopically at site and number of animals with lesion
Page 1
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 70 70 70 70
Scheduled Sacrifice 20 20 20 20
Early Deaths
Moribund Sacrifice 13 12 10 7
Natural Death 6 6 4 4
Survivors
Terminal Sacrifice 29 30 36 38
Moribund Sacrifice 1 1
Natural Death 2
Dead 1
Animals Examined Microscopically 70 70 70 70
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Esophagus (70) (70) (70) (69)
Angiectasis 1 (1%) 1 (1%)
Intestine Large, Colon (67) (67) (69) (69)
Parasite Metazoan 8 (12%) 7 (10%) 7 (10%) 4 (6%)
Intestine Large, Rectum (69) (67) (70) (70)
Parasite Metazoan 7 (10%) 5 (7%) 4 (6%) 6 (9%)
Intestine Large, Cecum (66) (65) (69) (68)
Autolysis 1 (2%)
Dilatation 1 (2%)
Inflammation, Chronic 1 (1%)
Parasite Metazoan 3 (5%) 3 (5%) 5 (7%) 8 (12%)
Intestine Small, Ileum (66) (63) (67) (68)
Abscess 1 (1%)
Parasite Metazoan 1 (1%)
Liver (70) (70) (70) (70)
Abscess 2 (3%)
Angiectasis 1 (1%) 4 (6%) 4 (6%)
Angiectasis, Focal 1 (1%)
Atrophy 1 (1%)
Basophilic Focus 42 (60%) 48 (69%) 41 (59%) 48 (69%)
Clear Cell Focus 11 (16%) 8 (11%) 4 (6%) 10 (14%)
Depletion Glycogen 1 (1%)
Developmental Malformation 1 (1%) 1 (1%)
Eosinophilic Focus 1 (1%)
Fatty Change 8 (11%) 6 (9%) 5 (7%) 7 (10%)
Granuloma 3 (4%) 5 (7%) 7 (10%) 8 (11%)
Hemorrhage 1 (1%) 1 (1%)
Hepatodiaphragmatic Nodule 7 (10%) 3 (4%) 5 (7%) 6 (9%)
Hepatodiaphragmatic Nodule, Multiple 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Mineralization, Focal 1 (1%)
Necrosis, Focal 1 (1%) 5 (7%) 1 (1%)
Pigmentation, Bile 1 (1%)
Bile Duct, Hyperplasia 4 (6%) 1 (1%) 5 (7%) 1 (1%)
Mesentery (4) (7) (9) (3)
Accessory Spleen 1 (33%)
Inflammation, Granulomatous 1 (14%)
Fat, Necrosis 3 (75%) 6 (86%) 8 (89%) 2 (67%)
Pancreas (70) (69) (70) (70)
Ectopic Liver 2 (3%)
Inflammation, Chronic, Focal 2 (3%)
Acinus, Atrophy 13 (19%) 11 (16%) 18 (26%) 13 (19%)
Acinus, Hyperplasia, Focal 1 (1%)
Artery, Inflammation, Chronic 1 (1%)
Salivary Glands (70) (70) (70) (70)
Depletion Cellular 2 (3%)
Hyperplasia 1 (1%) 1 (1%)
Hypoplasia 1 (1%)
Inflammation, Chronic, Focal 2 (3%)
Stomach, Forestomach (70) (68) (70) (70)
Acanthosis 1 (1%)
Diverticulum 1 (1%)
Hyperkeratosis 1 (1%)
Hyperplasia, Squamous 2 (3%)
Inflammation, Subacute 1 (1%)
Ulcer 1 (1%) 1 (1%) 1 (1%)
Stomach, Glandular (70) (69) (70) (70)
Depletion Cellular 1 (1%) 1 (1%) 1 (1%)
Edema, Focal 1 (1%)
Erosion 5 (7%) 8 (12%) 3 (4%) 5 (7%)
Hypoplasia 1 (1%)
Ulcer 1 (1%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (70) (70) (70) (70)
Cardiomyopathy 25 (36%) 23 (33%) 24 (34%) 26 (37%)
Dilatation 1 (1%) 1 (1%)
Inflammation, Chronic, Focal 2 (3%) 5 (7%) 6 (9%) 4 (6%)
Mineralization 1 (1%)
Pigmentation 1 (1%)
Artery, Mineralization 1 (1%)
Coronary Artery, Inflammation, Chronic 1 (1%)
Myocardium, Inflammation, Chronic, Focal 2 (3%) 1 (1%)
Perivascular, Inflammation 1 (1%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (70) (69) (70) (69)
Atrophy 1 (1%)
Congestion 1 (1%)
Cytoplasmic Alteration, Focal 3 (4%) 8 (12%) 8 (11%) 3 (4%)
Hyperplasia, Focal 1 (1%) 3 (4%)
Mineralization, Focal 1 (1%)
Vacuolization Cytoplasmic 3 (4%) 2 (3%) 2 (3%)
Adrenal Medulla (70) (69) (70) (70)
Fibrosis 1 (1%)
Hyperplasia, Focal 7 (10%) 4 (6%) 3 (4%) 2 (3%)
Necrosis 1 (1%)
Islets, Pancreatic (70) (69) (70) (70)
Hyperplasia 1 (1%)
Hypoplasia 2 (3%) 2 (3%) 4 (6%)
Parathyroid Gland (67) (66) (65) (61)
Hyperplasia 1 (2%)
Hyperplasia, Focal 2 (3%) 1 (2%)
Pituitary Gland (70) (69) (69) (67)
Hemorrhage 1 (1%) 1 (1%)
Pars Distalis, Angiectasis 5 (7%) 3 (4%) 2 (3%) 2 (3%)
Pars Distalis, Angiectasis, Focal 1 (1%)
Pars Distalis, Cyst 11 (16%) 7 (10%) 7 (10%) 8 (12%)
Pars Distalis, Hyperplasia 2 (3%) 1 (1%)
Pars Distalis, Hyperplasia, Focal 14 (20%) 16 (23%) 12 (17%) 11 (16%)
Thyroid Gland (70) (70) (70) (70)
Inflammation, Chronic, Focal 1 (1%)
C-Cell, Hyperplasia 14 (20%) 12 (17%) 14 (20%) 12 (17%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (65) (68) (69) (69)
Abscess 4 (6%)
Cyst 4 (6%) 4 (6%) 1 (1%) 3 (4%)
Depletion Cellular 2 (3%)
Dilatation 10 (15%) 4 (6%) 5 (7%) 9 (13%)
Inflammation, Acute 4 (6%) 2 (3%) 3 (4%) 2 (3%)
Inflammation, Chronic 13 (20%) 8 (12%) 11 (16%) 11 (16%)
Inflammation, Chronic, Focal 6 (9%) 8 (12%) 9 (13%) 8 (12%)
Ovary (70) (70) (70) (70)
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT
Angiectasis 1 (1%) 1 (1%)
Atrophy 1 (1%)
Cyst 1 (1%) 6 (9%) 2 (3%)
Inflammation, Chronic, Focal 1 (1%)
Uterus (70) (70) (70) (70)
Abscess 1 (1%)
Angiectasis 1 (1%) 1 (1%)
Atrophy 1 (1%) 2 (3%)
Cyst 2 (3%)
Dilatation 7 (10%) 6 (9%) 10 (14%) 6 (9%)
Thrombosis 2 (3%) 1 (1%)
Endometrium, Cyst 1 (1%) 1 (1%) 1 (1%)
Endometrium, Fibrosis 1 (1%) 2 (3%)
Endometrium, Hyperplasia, Cystic 2 (3%) 1 (1%)
Vagina (1) (1) (4) (1)
Dilatation 1 (100%) 1 (25%)
Exudate 1 (100%) 1 (25%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Blood (2) (1) (1)
Bacterium 1 (100%)
Hypochromasia 1 (100%)
Bone Marrow (70) (70) (70) (70)
Hyperplasia 17 (24%) 11 (16%) 15 (21%) 12 (17%)
Myelofibrosis 3 (4%) 1 (1%) 2 (3%)
Lymph Node (8) (6) (12) (8)
Inguinal, Congestion 1 (13%)
Lumbar, Congestion 1 (13%)
Lumbar, Hyperplasia 1 (8%)
Mediastinal, Angiectasis 1 (17%) 1 (8%)
Mediastinal, Congestion 1 (13%) 2 (17%) 1 (13%)
Mediastinal, Hematopoietic Cell Proliferation 1 (8%)
Mediastinal, Lymphatic, Angiectasis 1 (8%)
Pancreatic, Angiectasis 1 (17%) 1 (13%)
Pancreatic, Congestion 1 (13%)
Pancreatic, Giant Cell 2 (25%)
Pancreatic, Granuloma 1 (8%)
Pancreatic, Infiltration Cellular, Histiocyte 1 (13%)
Pancreatic, Pigmentation, Hemosiderin 2 (25%)
Pancreatic, Lymphatic, Angiectasis 1 (8%) 2 (25%)
Lymph Node, Mandibular (70) (70) (70) (69)
Congestion 1 (1%) 1 (1%) 1 (1%) 3 (4%)
Cyst 1 (1%)
Giant Cell 1 (1%) 1 (1%) 1 (1%)
Infiltration Cellular, Plasma Cell 1 (1%) 1 (1%) 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Infiltration Cellular, Histiocyte 1 (1%) 1 (1%)
Inflammation, Acute 1 (1%)
Lymphatic, Angiectasis 1 (1%) 2 (3%)
Lymph Node, Mesenteric (70) (69) (68) (70)
Congestion 3 (4%) 1 (1%) 3 (4%) 4 (6%)
Depletion Lymphoid 1 (1%) 1 (1%)
Giant Cell 10 (14%) 10 (14%) 8 (12%) 10 (14%)
Granuloma 1 (1%) 1 (1%)
Spleen (70) (69) (70) (70)
Autolysis 1 (1%)
Congestion 1 (1%)
Depletion Lymphoid 4 (6%) 1 (1%) 6 (9%) 9 (13%)
Fibrosis, Focal 1 (1%) 1 (1%) 3 (4%) 1 (1%)
Granuloma 1 (1%) 1 (1%)
Hematopoietic Cell Proliferation 4 (6%) 2 (3%) 4 (6%) 3 (4%)
Infarct 1 (1%) 1 (1%)
Necrosis, Focal 1 (1%)
Pigmentation, Hemosiderin 1 (1%)
Capsule, Fibrosis 1 (1%) 1 (1%)
Thymus (68) (68) (70) (65)
Cyst 3 (5%)
Depletion Lymphoid 2 (3%) 2 (3%) 1 (1%) 1 (2%)
Hyperplasia 1 (1%)
Lymphatic, Angiectasis 1 (1%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (69) (69) (66) (70)
Galactocele 9 (13%) 5 (7%) 2 (3%) 1 (1%)
Galactocele, Multiple 1 (1%) 1 (1%)
Lactation 35 (51%) 36 (52%) 27 (41%) 25 (36%)
Skin (70) (70) (69) (70)
Acanthosis 1 (1%)
Cyst Epithelial Inclusion 1 (1%)
Fibrosis 1 (1%)
Hyperkeratosis 1 (1%) 1 (1%)
Perivascular, Inflammation, Chronic 1 (1%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (70) (70) (70) (70)
Hyperostosis 6 (9%) 9 (13%) 12 (17%) 8 (11%)
Skeletal Muscle (1) (1) (1)
Ectopic Tissue 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (70) (70) (69) (70)
Abscess 1 (1%)
Compression 4 (6%) 6 (9%) 4 (6%) 4 (6%)
Congestion 1 (1%)
Hemorrhage 1 (1%) 4 (6%) 2 (3%) 4 (6%)
Capillary, Inflammation, Chronic 2 (3%)
Choroid Plexus, Inflammation, Chronic 1 (1%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (70) (70) (70) (70)
Angiectasis 2 (3%) 2 (3%)
Congestion 1 (1%)
Emphysema, Focal 1 (1%)
Granuloma 1 (1%)
Hemorrhage, Focal 1 (1%)
Mineralization, Focal 1 (1%)
Necrosis, Focal 3 (4%)
Alveolar Epithelium, Metaplasia 2 (3%) 1 (1%) 1 (1%)
Peribronchial, Inflammation, Chronic 10 (14%) 10 (14%) 9 (13%) 10 (14%)
Pleura, Fibrosis, Focal 1 (1%)
Nose (70) (70) (69) (70)
Fungus 4 (6%) 4 (6%) 3 (4%) 3 (4%)
Inflammation, Acute 2 (3%) 1 (1%) 5 (7%) 10 (14%)
Inflammation, Chronic 10 (14%) 12 (17%) 16 (23%) 14 (20%)
Inflammation, Chronic, Focal 10 (14%) 10 (14%) 9 (13%) 8 (11%)
Metaplasia, Squamous 3 (4%) 1 (1%) 1 (1%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (3) (1) (2)
Cataract 1 (100%) 1 (50%)
Retina, Degeneration 1 (33%)
Harderian Gland (2) (2)
Hyperplasia 1 (50%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (70) (69) (68) (69)
Abscess 1 (1%)
Bacterium 1 (1%)
Cyst 1 (1%) 1 (1%) 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Glomerulosclerosis 2 (3%) 1 (1%)
Mineralization 19 (27%) 22 (32%) 20 (29%) 20 (29%)
Mineralization, Focal 2 (3%) 5 (7%) 7 (10%)
Nephropathy 46 (66%) 49 (71%) 39 (57%) 40 (58%)
Pigmentation 1 (1%)
Renal Tubule, Degeneration, Granular 1 (1%) 1 (1%) 1 (1%)
Renal Tubule, Necrosis, Focal 1 (1%)
Renal Tubule, Pigmentation, Bile 4 (6%) 6 (9%) 1 (1%) 2 (3%)
Renal Tubule, Regeneration 1 (1%) 2 (3%) 1 (1%) 2 (3%)
Urinary Bladder (67) (64) (67) (68)
Hemorrhage 2 (3%)
Hyperplasia, Focal 1 (2%)
Inflammation, Chronic, Focal 1 (1%) 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 70 70 70 70
Scheduled Sacrifice 20 20 20 19
Early Deaths
Moribund Sacrifice 14 9 7 9
Natural Death 8 7 9 8
Accidently Killed 1
Survivors
Terminal Sacrifice 28 33 34 33
Natural Death 1
Animals Examined Microscopically 70 70 70 70
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Colon (66) (66) (65) (66)
Parasite Metazoan 8 (12%) 8 (12%) 11 (17%) 9 (14%)
Intestine Large, Rectum (68) (67) (68) (69)
Parasite Metazoan 10 (15%) 15 (22%) 15 (22%) 12 (17%)
Intestine Large, Cecum (66) (64) (64) (63)
Edema 2 (3%)
Hyperplasia, Lymphoid 1 (2%) 1 (2%)
Parasite Metazoan 3 (5%) 4 (6%) 3 (5%) 3 (5%)
Intestine Small, Jejunum (65) (66) (64) (65)
Hyperplasia, Lymphoid 1 (2%) 1 (2%)
Intestine Small, Ileum (66) (63) (62) (64)
Autolysis 1 (2%)
Peyer's Patch, Hyperplasia 1 (2%)
Liver (70) (70) (70) (70)
Angiectasis, Focal 2 (3%) 7 (10%) 3 (4%) 5 (7%)
Atrophy 1 (1%) 2 (3%)
Basophilic Focus 39 (56%) 46 (66%) 41 (59%) 39 (56%)
Clear Cell Focus 10 (14%) 8 (11%) 14 (20%) 6 (9%)
Cyst 2 (3%) 1 (1%)
Developmental Malformation 3 (4%) 1 (1%) 3 (4%) 7 (10%)
Eosinophilic Focus 2 (3%) 1 (1%) 4 (6%)
Fatty Change 9 (13%) 5 (7%) 4 (6%) 6 (9%)
Fibrosis, Focal 1 (1%) 1 (1%)
Granuloma 1 (1%) 3 (4%) 1 (1%)
Hepatodiaphragmatic Nodule 3 (4%) 3 (4%) 3 (4%) 4 (6%)
Infarct 1 (1%)
Mixed Cell Focus 1 (1%) 1 (1%)
Necrosis, Focal 3 (4%) 1 (1%) 1 (1%) 1 (1%)
Proliferation 1 (1%)
Thrombosis 1 (1%) 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 9
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Bile Duct, Dilatation 1 (1%)
Bile Duct, Hyperplasia 24 (34%) 31 (44%) 19 (27%) 22 (31%)
Lymphatic, Angiectasis, Focal 2 (3%) 1 (1%) 4 (6%) 3 (4%)
Mesentery (6) (7) (14) (14)
Accessory Spleen 1 (17%) 1 (7%) 1 (7%)
Cyst 1 (7%)
Fibrosis 1 (7%) 1 (7%)
Artery, Inflammation, Chronic 1 (7%)
Artery, Thrombosis 1 (7%)
Fat, Hemorrhage 1 (17%)
Fat, Necrosis 3 (50%) 5 (71%) 10 (71%) 11 (79%)
Pancreas (69) (70) (69) (69)
Angiectasis 1 (1%)
Autolysis, Focal 1 (1%)
Inflammation, Chronic, Focal 1 (1%)
Pigmentation, Focal 1 (1%)
Acinus, Atrophy 21 (30%) 28 (40%) 22 (32%) 24 (35%)
Acinus, Hyperplasia, Focal 2 (3%) 2 (3%) 1 (1%)
Artery, Hypertrophy 1 (1%)
Artery, Inflammation, Chronic 1 (1%) 2 (3%)
Vein, Thrombosis 1 (1%)
Pharynx (1)
Palate, Inflammation, Chronic 1 (100%)
Salivary Glands (69) (70) (69) (70)
Atrophy 1 (1%) 1 (1%)
Hyperplasia 1 (1%) 1 (1%)
Thrombosis 1 (1%)
Stomach, Forestomach (69) (70) (70) (70)
Cyst Epithelial Inclusion 1 (1%)
Hyperkeratosis 1 (1%) 1 (1%)
Inflammation, Chronic, Focal 1 (1%)
Ulcer 3 (4%) 1 (1%)
Stomach, Glandular (68) (70) (68) (70)
Erosion 8 (12%) 5 (7%) 3 (4%) 3 (4%)
Hyperplasia, Lymphoid 4 (6%) 2 (3%) 2 (3%)
Ulcer 1 (1%)
Mucosa, Inflammation, Acute 1 (1%)
Submucosa, Fibrosis 1 (1%)
Tongue (1)
Hyperkeratosis, Focal 1 (100%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 10
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (70) (70) (70) (70)
Cardiomyopathy 56 (80%) 50 (71%) 49 (70%) 45 (64%)
Hypertrophy 1 (1%)
Inflammation, Chronic, Focal 2 (3%) 6 (9%) 5 (7%) 3 (4%)
Mineralization 4 (6%) 1 (1%) 1 (1%)
Artery, Inflammation, Chronic 1 (1%) 1 (1%) 1 (1%) 1 (1%)
Atrium, Dilatation 1 (1%) 1 (1%) 2 (3%)
Atrium, Thrombosis 6 (9%) 3 (4%) 1 (1%)
Ventricle, Dilatation 1 (1%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (70) (69) (69) (69)
Cytoplasmic Alteration 1 (1%)
Cytoplasmic Alteration, Focal 2 (3%) 4 (6%) 1 (1%) 2 (3%)
Hyperplasia 2 (3%)
Hyperplasia, Focal 1 (1%)
Hypertrophy 1 (1%)
Vacuolization Cytoplasmic 3 (4%) 2 (3%) 1 (1%)
Adrenal Medulla (69) (68) (69) (69)
Hemorrhage 1 (1%) 1 (1%)
Hyperplasia, Focal 16 (23%) 12 (18%) 17 (25%) 22 (32%)
Islets, Pancreatic (69) (70) (70) (69)
Hyperplasia 4 (6%) 1 (1%)
Parathyroid Gland (67) (66) (68) (63)
Ectopic Thymus 1 (1%)
Hyperplasia, Focal 2 (3%) 1 (2%) 1 (1%)
Pituitary Gland (68) (69) (68) (70)
Pars Distalis, Angiectasis 1 (1%) 2 (3%) 1 (1%)
Pars Distalis, Cyst 1 (1%) 3 (4%) 3 (4%) 2 (3%)
Pars Distalis, Hemorrhage 1 (1%) 1 (1%)
Pars Distalis, Hyperplasia, Focal 10 (15%) 14 (20%) 17 (25%) 16 (23%)
Pars Distalis, Inflammation, Chronic, Focal 1 (1%)
Pars Intermedia, Cyst 1 (1%) 1 (1%)
Pars Intermedia, Hyperplasia, Focal 1 (1%)
Thyroid Gland (70) (69) (70) (69)
Ultimobranchial Cyst 1 (1%)
C-Cell, Hyperplasia 5 (7%) 6 (9%) 8 (11%) 7 (10%)
Follicle, Cyst 2 (3%) 1 (1%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 11
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (70) (69) (70) (70)
Atrophy 1 (1%)
Depletion Cellular 2 (3%) 2 (3%) 2 (3%) 6 (9%)
Dilatation 1 (1%)
Fibrosis 1 (1%)
Spermatocele 1 (1%)
Preputial Gland (70) (67) (70) (70)
Abscess 7 (10%) 4 (6%) 3 (4%)
Cyst 4 (6%) 5 (7%) 2 (3%) 2 (3%)
Ectasia 5 (7%) 2 (3%) 1 (1%) 3 (4%)
Hyperplasia 1 (1%)
Inflammation, Acute 5 (7%) 1 (1%)
Inflammation, Chronic 17 (24%) 11 (16%) 11 (16%) 15 (21%)
Inflammation, Chronic, Focal 8 (11%) 8 (12%) 8 (11%) 9 (13%)
Metaplasia, Squamous 1 (1%)
Prostate (69) (70) (69) (70)
Atrophy 18 (26%) 11 (16%) 12 (17%) 18 (26%)
Congestion 1 (1%)
Dilatation 2 (3%) 1 (1%) 1 (1%)
Hyperplasia, Focal 1 (1%)
Inflammation, Acute 1 (1%) 2 (3%)
Inflammation, Chronic 1 (1%) 1 (1%)
Inflammation, Focal 1 (1%)
Seminal Vesicle (68) (70) (69) (70)
Atrophy 36 (53%) 36 (51%) 38 (55%) 41 (59%)
Cyst 1 (1%)
Dilatation 1 (1%) 3 (4%) 2 (3%) 2 (3%)
Testes (70) (69) (70) (70)
Hemorrhage, Focal 1 (1%)
Bilateral, Interstitial Cell, Hyperplasia 4 (6%) 1 (1%) 5 (7%) 4 (6%)
Interstitial Cell, Hyperplasia 1 (1%) 5 (7%) 2 (3%) 1 (1%)
Seminiferous Tubule, Atrophy 3 (4%) 5 (7%) 2 (3%) 3 (4%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (69) (70) (70) (70)
Granuloma 1 (1%)
Hyperplasia 22 (32%) 19 (27%) 23 (33%) 21 (30%)
Myelofibrosis 1 (1%) 2 (3%) 2 (3%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 12
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Lymph Node (12) (19) (16) (11)
Inguinal, Lymphatic, Angiectasis 1 (5%)
Lumbar, Lymphatic, Angiectasis 1 (6%)
Mediastinal, Congestion 1 (8%) 1 (5%) 1 (6%)
Mediastinal, Granuloma 1 (5%)
Mediastinal, Pigmentation 1 (5%)
Mediastinal, Lymphatic, Angiectasis 4 (33%) 2 (11%) 3 (19%) 2 (18%)
Pancreatic, Hyperplasia, Lymphoid 1 (5%)
Pancreatic, Lymphatic, Angiectasis 2 (17%) 4 (21%) 4 (25%) 2 (18%)
Renal, Pigmentation 1 (6%)
Renal, Lymphatic, Angiectasis 1 (6%)
Lymph Node, Mandibular (68) (69) (68) (70)
Angiectasis 4 (6%) 2 (3%) 4 (6%) 3 (4%)
Congestion 1 (1%) 1 (1%) 4 (6%)
Depletion Lymphoid 1 (1%)
Infiltration Cellular, Plasma Cell 2 (3%) 1 (1%) 1 (1%)
Lymphatic, Angiectasis 1 (1%) 2 (3%) 1 (1%)
Lymph Node, Mesenteric (69) (70) (68) (69)
Angiectasis 5 (7%) 5 (7%) 2 (3%) 3 (4%)
Congestion 1 (1%) 1 (1%)
Depletion Lymphoid 1 (1%) 1 (1%) 1 (1%) 1 (1%)
Giant Cell 8 (12%) 10 (14%) 10 (15%) 8 (12%)
Hyperplasia, Lymphoid 1 (1%)
Lymphatic, Angiectasis 1 (1%) 2 (3%) 3 (4%) 3 (4%)
Spleen (70) (70) (70) (70)
Congestion 1 (1%) 2 (3%) 1 (1%) 1 (1%)
Depletion Lymphoid 3 (4%) 2 (3%) 6 (9%) 6 (9%)
Fibrosis 14 (20%) 17 (24%) 9 (13%) 11 (16%)
Hematopoietic Cell Proliferation 3 (4%) 2 (3%) 1 (1%)
Hemorrhage 1 (1%)
Hypertrophy 1 (1%)
Infarct 2 (3%) 7 (10%) 1 (1%)
Inflammation, Acute 1 (1%)
Necrosis, Focal 1 (1%) 1 (1%)
Pigmentation, Hemosiderin 3 (4%)
Thrombosis 1 (1%) 1 (1%)
Capsule, Congestion, Focal 1 (1%)
Capsule, Fibrosis 2 (3%) 1 (1%) 1 (1%)
Thymus (59) (67) (67) (68)
Congestion 1 (1%)
Cyst 2 (3%)
Depletion Lymphoid 1 (2%) 2 (3%) 5 (7%)
Hemorrhage, Focal 1 (1%)
Hyperplasia, Lymphoid 1 (1%)
Lymphatic, Angiectasis 1 (1%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 13
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (57) (53) (53) (61)
Lactation 14 (25%) 14 (26%) 12 (23%) 12 (20%)
Skin (70) (70) (68) (70)
Abscess 1 (1%)
Acanthosis 1 (1%)
Cyst Epithelial Inclusion 1 (1%)
Edema 1 (1%)
Fibrosis, Focal 2 (3%) 1 (1%) 1 (1%)
Inflammation, Focal, Granulomatous 1 (1%)
Ulcer 1 (1%) 1 (1%) 1 (1%)
Hair Follicle, Cyst 1 (1%)
Subcutaneous Tissue, Hemorrhage 1 (1%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (69) (70) (70) (70)
Callus 1 (1%)
Hyperostosis 5 (7%) 2 (3%) 3 (4%) 3 (4%)
Proliferation 1 (1%)
Skeletal Muscle (1) (6)
Fibrosis 2 (33%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (70) (70) (70) (70)
Compression 2 (3%) 2 (3%)
Hemorrhage 1 (1%) 2 (3%) 3 (4%)
Meninges, Hemorrhage 1 (1%)
Peripheral Nerve (1) (1)
Degeneration 1 (100%)
Spinal Cord (1) (1) (1)
Degeneration 1 (100%)
Hemorrhage, Focal 1 (100%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (70) (70) (70) (70)
Angiectasis 3 (4%)
Congestion 1 (1%)
Granuloma 3 (4%)
Hemorrhage, Focal 1 (1%) 1 (1%) 1 (1%)
Hyperplasia, Adenomatous 1 (1%)
Infiltration Cellular, Focal, Histiocyte 5 (7%) 1 (1%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 14
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Peribronchial, Inflammation, Chronic 11 (16%) 10 (14%) 9 (13%) 11 (16%)
Pleura, Inflammation, Chronic, Focal 1 (1%)
Nose (70) (69) (69) (70)
Fungus 18 (26%) 18 (26%) 16 (23%) 15 (21%)
Hyperkeratosis 1 (1%) 1 (1%) 1 (1%)
Hyperplasia, Basal Cell 2 (3%)
Inflammation, Acute 4 (6%) 9 (13%) 1 (1%) 9 (13%)
Inflammation, Chronic 10 (14%) 7 (10%) 13 (19%) 15 (21%)
Inflammation, Chronic, Focal 10 (14%) 10 (14%) 10 (14%) 7 (10%)
Metaplasia, Squamous 4 (6%) 1 (1%) 2 (3%)
Respiratory Epithelium, Necrosis 1 (1%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (1) (3) (3) (3)
Cataract 1 (33%) 3 (100%) 3 (100%)
Retina, Degeneration 1 (100%) 2 (67%) 1 (33%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (69) (70) (70) (67)
Abscess 1 (1%)
Autolysis 1 (1%)
Cyst 2 (3%) 1 (1%)
Glomerulosclerosis 1 (1%) 1 (1%)
Mineralization 1 (1%)
Necrosis, Focal 1 (1%)
Nephropathy 56 (81%) 57 (81%) 59 (84%) 57 (85%)
Medulla, Casts 1 (1%)
Papilla, Necrosis 1 (1%)
Pelvis, Epithelium, Hyperplasia 1 (1%)
Renal Tubule, Degeneration, Granular 2 (3%) 2 (3%) 2 (3%)
Renal Tubule, Pigmentation, Bile 3 (4%) 2 (3%) 5 (7%) 4 (6%)
Renal Tubule, Regeneration 5 (7%) 4 (6%) 6 (9%) 1 (1%)
Ureter (1)
Hyperplasia 1 (100%)
Urinary Bladder (63) (64) (63) (64)
Calculus Micro Observation Only 5 (8%) 1 (2%) 3 (5%)
Ectasia 1 (2%)
Hemorrhage 1 (2%) 1 (2%)
Inflammation, Chronic, Focal 1 (2%)
Ulcer 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 15
NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95
Route: DOSED FEED Time: 09:09:24
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Transitional Epithelium, Hyperplasia 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 16
------------------------------------------------------------
---------- END OF REPORT ----------
------------------------------------------------------------