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 ---------- ------------------------------------------------------------