TDMS Study 05150-01 Pathology Tables
INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) METHLYPHENIDATE HYDROCHLORIDE NTP Experiment-Test: 05150-01 Report: PEIRPT05 Study Type: CHRONIC Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 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 NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ 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 Intestine Large, Colon (67) (67) (69) (69) Fibroma 1 (1%) Intestine Small, Duodenum (67) (66) (70) (69) Sarcoma Stromal, Metastatic, Uterus 1 (1%) Intestine Small, Jejunum (67) (63) (68) (68) Intestine Small, Ileum (66) (63) (67) (68) Sarcoma 1 (1%) Liver (70) (70) (70) (70) Hepatocellular Adenoma 1 (1%) Sarcoma Stromal, Metastatic, Uterus 1 (1%) Mesentery (4) (7) (9) (3) Sarcoma Stromal, Metastatic, Uterus 1 (25%) Pancreas (70) (69) (70) (70) Sarcoma Stromal, Metastatic, Uterus 1 (1%) Salivary Glands (70) (70) (70) (70) Stomach, Forestomach (70) (68) (70) (70) Squamous Cell Papilloma 1 (1%) Stomach, Glandular (70) (69) (70) (70) Tongue (1) (1) Squamous Cell Papilloma 1 (100%) 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (70) (70) (70) (70) ____________________________________________________________________________________________________________________________________ Page 2 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Medulla (70) (69) (70) (70) Pheochromocytoma Malignant 1 (1%) 2 (3%) Pheochromocytoma Benign 3 (4%) 3 (4%) 3 (4%) 3 (4%) Islets, Pancreatic (70) (69) (70) (70) Adenoma 2 (3%) 1 (1%) 2 (3%) Parathyroid Gland (67) (66) (65) (61) Adenoma 1 (2%) Pituitary Gland (70) (69) (69) (67) Pars Distalis, Adenoma 28 (40%) 30 (43%) 17 (25%) 22 (33%) Pars Distalis, Adenoma, Multiple 3 (4%) 5 (7%) 3 (4%) Pars Distalis, Carcinoma 1 (1%) Thyroid Gland (70) (70) (70) (70) C-Cell, Adenoma 4 (6%) 8 (11%) 7 (10%) 4 (6%) C-Cell, Carcinoma 1 (1%) 2 (3%) 1 (1%) Follicular Cell, Adenoma 1 (1%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (65) (68) (69) (69) Adenoma 1 (2%) 1 (1%) 1 (1%) Ovary (70) (70) (70) (70) Adenoma, Tubular 1 (1%) Granulosa Cell Tumor Benign 1 (1%) Uterus (70) (70) (70) (70) Leiomyoma 1 (1%) Polyp Stromal 5 (7%) 9 (13%) 11 (16%) 8 (11%) Polyp Stromal, Two 1 (1%) Sarcoma Stromal 2 (3%) 1 (1%) 1 (1%) 1 (1%) Vagina (1) (1) (4) (1) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Blood (2) (1) (1) Bone Marrow (70) (70) (70) (70) Lymph Node (8) (6) (12) (8) Lymph Node, Mandibular (70) (70) (70) (69) Fibrosarcoma, Metastatic, Skin 1 (1%) Lymph Node, Mesenteric (70) (69) (68) (70) Sarcoma Stromal, Metastatic, Uterus 1 (1%) Page 3 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - cont Spleen (70) (69) (70) (70) Thymus (68) (68) (70) (65) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (69) (69) (66) (70) Adenocarcinoma 1 (1%) 4 (6%) 1 (2%) 1 (1%) Adenoma 1 (2%) Fibroadenoma 10 (14%) 12 (17%) 6 (9%) 3 (4%) Fibroadenoma, Multiple 5 (7%) 1 (1%) 2 (3%) Fibrosarcoma 1 (1%) Skin (70) (70) (69) (70) Basal Cell Adenoma 1 (1%) 1 (1%) 1 (1%) Fibroma 2 (3%) Fibrosarcoma 1 (1%) Keratoacanthoma 1 (1%) Sarcoma 1 (1%) 1 (1%) Trichoepithelioma 1 (1%) Pinna, Neurofibroma 1 (1%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (70) (70) (70) (70) Osteosarcoma 1 (1%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (70) (70) (69) (70) Astrocytoma Malignant 1 (1%) Carcinoma, Metastatic, Pituitary Gland 1 (1%) Spinal Cord (1) (1) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (70) (70) (70) (70) Alveolar/Bronchiolar Adenoma 3 (4%) Carcinoma, Metastatic, Thyroid Gland 1 (1%) Fibrosarcoma, Metastatic, Skin 1 (1%) Pheochromocytoma Malignant, Metastatic, Adrenal Medulla 1 (1%) Squamous Cell Carcinoma, Metastatic, Ear 1 (1%) ____________________________________________________________________________________________________________________________________ Page 4 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Ear (1) Squamous Cell Carcinoma, Metastatic, Ear 1 (100%) Zymbal's Gland (1) (1) (1) Carcinoma 1 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (70) (69) (68) (69) Lipoma 1 (1%) Renal Tubule, Adenoma 1 (1%) 2 (3%) Urinary Bladder (67) (64) (67) (68) Papilloma 1 (1%) 1 (1%) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(70) *(70) *(70) *(70) Leukemia Mononuclear 13 (19%) 14 (20%) 14 (20%) 13 (19%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 5 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 49 51 50 46 Total Primary Neoplasms 77 105 77 75 Total Animals with Benign Neoplasms 43 48 42 38 Total Benign Neoplasms 59 80 56 57 Total Animals with Malignant Neoplasms 18 22 20 17 Total Malignant Neoplasms 18 25 21 18 Total Animals with Metastatic Neoplasms 2 3 1 Total Metastatic Neoplasm 7 4 1 Total Animals with Malignant Neoplasms Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant Total Uncertain Neoplasms ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 6 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ 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) Intestine Large, Rectum (68) (67) (68) (69) Intestine Large, Cecum (66) (64) (64) (63) Lipoma 1 (2%) Polyp 1 (2%) Intestine Small, Duodenum (66) (69) (66) (67) Intestine Small, Jejunum (65) (66) (64) (65) Intestine Small, Ileum (66) (63) (62) (64) Liver (70) (70) (70) (70) Hepatocellular Adenoma 2 (3%) Histiocytic Sarcoma 1 (1%) Mesentery (6) (7) (14) (14) Pancreas (69) (70) (69) (69) Acinus, Adenoma 2 (3%) 1 (1%) Stomach, Glandular (68) (70) (68) (70) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (70) (70) (70) (70) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (70) (69) (69) (69) Adenoma 1 (1%) Adrenal Medulla (69) (68) (69) (69) Pheochromocytoma Malignant 1 (1%) 1 (1%) 1 (1%) Pheochromocytoma Benign 12 (17%) 5 (7%) 5 (7%) 11 (16%) Page 7 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - cont Bilateral, Pheochromocytoma Benign 5 (7%) 1 (1%) Islets, Pancreatic (69) (70) (70) (69) Adenoma 1 (1%) 1 (1%) 2 (3%) Carcinoma 2 (3%) 2 (3%) Parathyroid Gland (67) (66) (68) (63) Adenoma 1 (2%) Pituitary Gland (68) (69) (68) (70) Pars Distalis, Adenoma 11 (16%) 11 (16%) 7 (10%) 11 (16%) Pars Distalis, Adenoma, Multiple 1 (1%) Pars Distalis, Carcinoma 1 (1%) Thyroid Gland (70) (69) (70) (69) Schwannoma Malignant, Metastatic, Skin 1 (1%) Bilateral, C-Cell, Adenoma 1 (1%) C-Cell, Adenoma 4 (6%) 5 (7%) 6 (9%) 8 (12%) C-Cell, Carcinoma 1 (1%) 2 (3%) 1 (1%) Follicular Cell, Adenoma 1 (1%) Follicular Cell, Carcinoma 1 (1%) 1 (1%) 1 (1%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Coagulating Gland (1) Adenoma 1 (100%) Epididymis (70) (69) (70) (70) Preputial Gland (70) (67) (70) (70) Adenoma 2 (3%) 2 (3%) 2 (3%) 1 (1%) Carcinoma 2 (3%) 4 (6%) 2 (3%) Prostate (69) (70) (69) (70) Seminal Vesicle (68) (70) (69) (70) Testes (70) (69) (70) (70) Bilateral, Interstitial Cell, Adenoma 50 (71%) 47 (68%) 51 (73%) 51 (73%) Interstitial Cell, Adenoma 5 (7%) 9 (13%) 4 (6%) 6 (9%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Blood (1) Bone Marrow (69) (70) (70) (70) Histiocytic Sarcoma 1 (1%) Osteosarcoma, Metastatic, Bone 1 (1%) Lymph Node (12) (19) (16) (11) Mediastinal, Histiocytic Sarcoma 1 (9%) Page 8 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - cont Pancreatic, Histiocytic Sarcoma 1 (9%) Lymph Node, Mandibular (68) (69) (68) (70) Histiocytic Sarcoma 1 (1%) Lymph Node, Mesenteric (69) (70) (68) (69) Histiocytic Sarcoma 1 (1%) Spleen (70) (70) (70) (70) Hemangiosarcoma 2 (3%) Histiocytic Sarcoma 1 (1%) Thymus (59) (67) (67) (68) Histiocytic Sarcoma 1 (1%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (57) (53) (53) (61) Fibroadenoma 1 (2%) 2 (4%) 1 (2%) 2 (3%) Skin (70) (70) (68) (70) Basal Cell Adenoma 2 (3%) Fibroma 1 (1%) 3 (4%) 1 (1%) 3 (4%) Fibrosarcoma 1 (1%) Keratoacanthoma 1 (1%) 1 (1%) 4 (6%) 1 (1%) Sarcoma 1 (1%) 1 (1%) Squamous Cell Papilloma 1 (1%) 1 (1%) Subcutaneous Tissue, Schwannoma Malignant 1 (1%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (69) (70) (70) (70) Chordoma 1 (1%) Osteosarcoma 1 (1%) Skeletal Muscle (1) (6) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (70) (70) (70) (70) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (70) (70) (70) (70) Alveolar/Bronchiolar Adenoma 2 (3%) 1 (1%) Histiocytic Sarcoma 1 (1%) Schwannoma Malignant, Metastatic, Skin 1 (1%) Nose (70) (69) (69) (70) Polyp 1 (1%) Page 9 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - cont Squamous Cell Carcinoma 1 (1%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Ear (3) (1) Carcinoma, Metastatic, Pituitary Gland 1 (33%) Zymbal's Gland (1) Carcinoma 1 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (69) (70) (70) (67) Lipoma 1 (1%) Sarcoma 1 (1%) Renal Tubule, Adenoma 1 (1%) Urinary Bladder (63) (64) (63) (64) Papilloma 1 (2%) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(70) *(70) *(70) *(70) Histiocytic Sarcoma 1 (1%) Leukemia Mononuclear 29 (41%) 25 (36%) 17 (24%) 23 (33%) Mesothelioma Malignant 1 (1%) 3 (4%) 2 (3%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 10 NTP Experiment-Test: 05150-01 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC METHLYPHENIDATE HYDROCHLORIDE Date: 05/20/95 Route: DOSED FEED Time: 09:09:25 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 100 PPM 500 PPM 1000 PPM ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 57 57 56 57 Total Primary Neoplasms 135 126 118 137 Total Animals with Benign Neoplasms 56 57 55 57 Total Benign Neoplasms 98 94 85 104 Total Animals with Malignant Neoplasms 32 28 27 30 Total Malignant Neoplasms 37 32 33 33 Total Animals with Metastatic Neoplasms 1 4 1 Total Metastatic Neoplasm 1 5 1 Total Animals with Malignant Neoplasms Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant Total Uncertain Neoplasms ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 11 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------