TDMS Study 05067-10 Pathology Tables
NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
CORE STUDY
Facility: Southern Research Institute
Chemical CAS #: 58-55-9
Lock Date: 07/14/93
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
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Moribund Sacrifice 7 4 11 9
Natural Death 6 9 5 8
Survivors
Terminal Sacrifice 37 37 34 33
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Gallbladder (46) (48) (47) (49)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Intestine Large, Colon (48) (49) (47) (48)
Intestine Large, Cecum (48) (45) (47) (47)
Leiomyosarcoma 1 (2%) 1 (2%)
Intestine Small, Jejunum (47) (46) (47) (43)
Leiomyosarcoma, Metastatic, Uterus 1 (2%)
Liver (50) (50) (50) (50)
Hepatocellular Carcinoma 8 (16%) 5 (10%) 6 (12%) 4 (8%)
Hepatocellular Carcinoma, Multiple 3 (6%) 1 (2%)
Hepatocellular Adenoma 17 (34%) 9 (18%) 9 (18%) 3 (6%)
Hepatocellular Adenoma, Multiple 3 (6%) 2 (4%) 3 (6%)
Hepatocholangiocarcinoma 1 (2%) 1 (2%) 1 (2%) 1 (2%)
Histiocytic Sarcoma 1 (2%) 6 (12%) 2 (4%) 2 (4%)
Ito Cell Tumor Malignant, Multiple 1 (2%)
Mesentery (10) (8) (6) (5)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (10%) 1 (13%) 1 (20%)
Histiocytic Sarcoma 1 (13%) 1 (20%)
Sarcoma 1 (10%)
Sarcoma, Metastatic, Skeletal Muscle 1 (13%)
Pancreas (50) (49) (49) (49)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%) 1 (2%) 1 (2%)
Histiocytic Sarcoma 1 (2%)
Leiomyosarcoma, Metastatic, Uterus 1 (2%)
Sarcoma, Metastatic, Skeletal Muscle 1 (2%)
Salivary Glands (50) (49) (50) (50)
Histiocytic Sarcoma 1 (2%)
Stomach, Forestomach (50) (49) (49) (50)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Squamous Cell Papilloma 4 (8%) 2 (4%) 2 (4%) 2 (4%)
Stomach, Glandular (49) (49) (48) (50)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%) 1 (2%) 1 (2%)
Sarcoma, Metastatic, Skeletal Muscle 1 (2%)
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (50) (50) (49)
Adenoma 1 (2%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Capsule, Adenoma 1 (2%)
Capsule, Hepatocholangiocarcinoma,
Metastatic, Liver 1 (2%) 1 (2%)
Capsule, Histiocytic Sarcoma 2 (4%) 1 (2%)
Adrenal Medulla (50) (48) (50) (49)
Pheochromocytoma Benign 1 (2%) 2 (4%) 2 (4%) 1 (2%)
Pituitary Gland (49) (45) (50) (48)
Pars Distalis, Adenoma 9 (18%) 7 (16%) 7 (14%) 5 (10%)
Pars Distalis, Histiocytic Sarcoma 1 (2%)
Thyroid Gland (50) (50) (50) (50)
Follicular Cell, Adenoma 4 (8%) 2 (4%) 3 (6%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Ovary (50) (50) (50) (50)
Cystadenoma 1 (2%) 1 (2%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%) 1 (2%) 1 (2%)
Histiocytic Sarcoma 4 (8%) 1 (2%) 1 (2%)
Uterus (50) (50) (50) (50)
Histiocytic Sarcoma 4 (8%) 3 (6%) 1 (2%)
Leiomyosarcoma 1 (2%)
Endometrium, Polyp Stromal 1 (2%) 1 (2%) 1 (2%)
Endometrium, Sarcoma Stromal 1 (2%)
____________________________________________________________________________________________________________________________________
Page 3
NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (49) (50)
Histiocytic Sarcoma 2 (4%) 1 (2%)
Lymph Node (6) (8) (7) (6)
Histiocytic Sarcoma 1 (13%)
Iliac, Histiocytic Sarcoma 2 (25%)
Inguinal, Histiocytic Sarcoma 1 (13%)
Mediastinal, Alveolar/Bronchiolar Carcinoma,
Metastatic, Liver 1 (13%)
Mediastinal, Hepatocholangiocarcinoma,
Metastatic, Liver 1 (17%) 1 (13%)
Mediastinal, Histiocytic Sarcoma 2 (25%)
Renal, Histiocytic Sarcoma 2 (25%)
Lymph Node, Mandibular (48) (49) (44) (43)
Histiocytic Sarcoma 3 (6%)
Lymph Node, Mesenteric (48) (46) (48) (45)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%) 1 (2%)
Histiocytic Sarcoma 3 (7%) 1 (2%)
Sarcoma, Metastatic, Mesentery 1 (2%)
Sarcoma, Metastatic, Skeletal Muscle 1 (2%)
Spleen (50) (50) (49) (48)
Hemangiosarcoma 2 (4%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Histiocytic Sarcoma 2 (4%) 1 (2%)
Thymus (47) (44) (49) (47)
Alveolar/Bronchiolar Carcinoma, Metastatic,
Lung 1 (2%)
Histiocytic Sarcoma 2 (5%) 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (49) (50) (50) (50)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Subcutaneous Tissue, Fibrosarcoma 1 (2%)
Subcutaneous Tissue, Hemangiosarcoma 1 (2%)
Subcutaneous Tissue, Histiocytic Sarcoma 1 (2%)
Subcutaneous Tissue, Sarcoma 1 (2%) 1 (2%)
Subcutaneous Tissue, Pinna, Histiocytic
Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50)
Cranium, Fibrosarcoma 1 (2%)
Skeletal Muscle (3) (3) (2) (1)
Fibrosarcoma 1 (33%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (33%) 1 (33%) 1 (100%)
Sarcoma 1 (33%) 1 (33%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Meninges, Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 2 (4%) 4 (8%) 4 (8%) 3 (6%)
Alveolar/Bronchiolar Adenoma, Multiple 1 (2%)
Alveolar/Bronchiolar Carcinoma 1 (2%) 1 (2%)
Hepatocellular Carcinoma, Metastatic, Liver 3 (6%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%) 1 (2%) 1 (2%)
Histiocytic Sarcoma 4 (8%) 1 (2%) 1 (2%)
Sarcoma, Metastatic, Uncertain Primary Site 1 (2%)
Sarcoma, Metastatic, Skeletal Muscle 1 (2%)
Mediastinum, Alveolar/Bronchiolar Carcinoma,
Metastatic, Lung 1 (2%)
Mediastinum, Hepatocholangiocarcinoma,
Metastatic, Liver 1 (2%)
Mediastinum, Sarcoma, Metastatic, Uncertain
Primary Site 1 (2%)
Nose (50) (50) (50) (50)
Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Harderian Gland (6) (6) (8) (2)
Adenoma 6 (100%) 5 (83%) 4 (50%) 2 (100%)
Carcinoma 2 (25%)
Histiocytic Sarcoma 1 (17%)
____________________________________________________________________________________________________________________________________
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50) (50) (50)
Histiocytic Sarcoma 3 (6%)
Urinary Bladder (49) (49) (49) (50)
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Histiocytic Sarcoma 1 (2%) 8 (16%) 4 (8%) 2 (4%)
Lymphoma Malignant 11 (22%) 8 (16%) 10 (20%) 8 (16%)
____________________________________________________________________________________________________________________________________
* Number of animals with any tissue examined microscopically
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 46 39 41 28
Total Primary Neoplasms 79 63 62 37
Total Animals with Benign Neoplasms 33 27 27 18
Total Benign Neoplasms 49 33 36 20
Total Animals with Malignant Neoplasms 26 24 22 17
Total Malignant Neoplasms 30 30 26 17
Total Animals with Metastatic Neoplasms 5 4 1 1
Total Metastatic Neoplasm 15 20 2 9
Total Animals with Malignant Neoplasms 1
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
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE VEHICLE 15 MG/KG 50 MG/KG 150
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Natural Death 5 6 4 15
Moribund Sacrifice 9 9 2 9
Survivors
Terminal Sacrifice 36 35 44 26
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Gallbladder (45) (46) (47) (42)
Adenoma 1 (2%)
Intestine Small, Duodenum (48) (49) (49) (41)
Leiomyosarcoma 1 (2%)
Intestine Small, Jejunum (48) (47) (47) (41)
Polyp Adenomatous 1 (2%)
Liver (50) (50) (50) (50)
Hemangiosarcoma 2 (4%) 1 (2%) 1 (2%)
Hemangiosarcoma, Multiple 2 (4%)
Hepatocellular Carcinoma 12 (24%) 13 (26%) 10 (20%) 2 (4%)
Hepatocellular Carcinoma, Multiple 7 (14%) 1 (2%) 2 (4%)
Hepatocellular Adenoma 14 (28%) 12 (24%) 10 (20%) 2 (4%)
Hepatocellular Adenoma, Multiple 7 (14%) 6 (12%) 2 (4%)
Histiocytic Sarcoma 1 (2%) 1 (2%) 1 (2%)
Mesentery (10) (4) (2)
Histiocytic Sarcoma 1 (10%) 1 (25%)
Sarcoma 1 (25%)
Pancreas (50) (49) (49) (50)
Stomach, Forestomach (50) (50) (50) (49)
Squamous Cell Carcinoma 1 (2%)
Squamous Cell Papilloma 1 (2%) 4 (8%) 1 (2%)
Stomach, Glandular (50) (49) (49) (43)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Carcinoma, Metastatic, Kidney 1 (2%)
____________________________________________________________________________________________________________________________________
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE VEHICLE 15 MG/KG 50 MG/KG 150
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (49)
Capsule, Adenoma 4 (8%) 2 (4%) 1 (2%) 1 (2%)
Adrenal Medulla (49) (50) (49) (49)
Pheochromocytoma Benign 1 (2%)
Islets, Pancreatic (50) (49) (50) (50)
Adenoma 1 (2%)
Pituitary Gland (49) (50) (48) (44)
Pars Intermedia, Adenoma 1 (2%)
Thyroid Gland (50) (50) (50) (50)
C-Cell, Adenoma 1 (2%)
Follicular Cell, Adenoma 1 (2%) 2 (4%)
Follicular Cell, Carcinoma 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Tissue NOS (1)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (49) (50) (50) (50)
Preputial Gland (49) (48) (50) (50)
Hemangiosarcoma 1 (2%)
Prostate (50) (49) (50) (50)
Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (50) (49)
Hemangiosarcoma 2 (4%) 1 (2%)
Histiocytic Sarcoma 1 (2%) 1 (2%)
Lymph Node (5) (6) (5) (3)
Mediastinal, Carcinoma, Metastatic, Lung 1 (20%)
Pancreatic, Histiocytic Sarcoma 1 (20%)
Renal, Histiocytic Sarcoma 1 (20%)
Lymph Node, Mandibular (42) (47) (47) (47)
Histiocytic Sarcoma 1 (2%)
Lymph Node, Mesenteric (50) (46) (50) (48)
Histiocytic Sarcoma 1 (2%) 1 (2%)
Spleen (50) (49) (50) (49)
Hemangiosarcoma 2 (4%) 1 (2%)
Histiocytic Sarcoma 1 (2%) 1 (2%)
Thymus (43) (42) (44) (46)
____________________________________________________________________________________________________________________________________
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE VEHICLE 15 MG/KG 50 MG/KG 150
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (50) (50) (50) (50)
Subcutaneous Tissue, Fibrosarcoma 1 (2%) 1 (2%)
Subcutaneous Tissue, Hemangiosarcoma 1 (2%)
Subcutaneous Tissue, Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Skeletal Muscle (1)
Hemangiosarcoma 1 (100%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
None
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 8 (16%) 6 (12%) 8 (16%) 3 (6%)
Alveolar/Bronchiolar Adenoma, Multiple 2 (4%) 2 (4%) 1 (2%)
Alveolar/Bronchiolar Carcinoma 6 (12%) 1 (2%) 5 (10%) 1 (2%)
Hepatocellular Carcinoma, Metastatic, Liver 6 (12%) 1 (2%)
Histiocytic Sarcoma 1 (2%) 1 (2%)
Sarcoma 1 (2%)
Nose (50) (50) (50) (50)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Harderian Gland (1) (4) (2) (2)
Adenoma 1 (100%) 3 (75%) 2 (100%) 2 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (49) (50) (50)
Carcinoma, Metastatic, Lung 1 (2%)
Renal Tubule, Adenoma 1 (2%)
Urinary Bladder (50) (49) (50) (50)
Histiocytic Sarcoma 1 (2%)
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NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE VEHICLE 15 MG/KG 50 MG/KG 150
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Histiocytic Sarcoma 1 (2%) 1 (2%) 1 (2%)
Lymphoma Malignant 5 (10%) 3 (6%) 5 (10%) 1 (2%)
____________________________________________________________________________________________________________________________________
* Number of animals with any tissue examined microscopically
Page 11
NTP Experiment-Test: 05067-10 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/03/96
Route: GAVAGE Time: 12:52:56
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE VEHICLE 15 MG/KG 50 MG/KG 150
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 44 42 38 13
Total Primary Neoplasms 76 69 54 16
Total Animals with Benign Neoplasms 29 29 22 9
Total Benign Neoplasms 36 40 27 12
Total Animals with Malignant Neoplasms 32 24 25 4
Total Malignant Neoplasms 40 29 27 4
Total Animals with Metastatic Neoplasms 7 1
Total Metastatic Neoplasm 9 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
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