TDMS Study 88036-03 Pathology Tables
NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 2 YEAR CHRONIC RATS Facility: Battelle Columbus Laboratory Chemical CAS #: 84-65-1 Lock Date: 07/23/97 Cage Range: All Reasons For Removal: 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice 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: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 60 50 50 50 60 Early Deaths Moribund Sacrifice 14 7 12 7 6 Natural Death 13 3 3 6 4 Survivors Terminal Sacrifice 23 40 35 37 40 Animals Examined Microscopically 50 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (50) (50) (49) (50) (49) Parasite Metazoan 2 (4%) 2 (4%) 1 (2%) Intestine Large, Rectum (50) (50) (49) (50) (50) Inflammation 1 (2%) Parasite Metazoan 6 (12%) 11 (22%) 2 (4%) 8 (16%) Intestine Large, Cecum (50) (49) (49) (50) (49) Inflammation 1 (2%) Intestine Small, Jejunum (50) (50) (50) (50) (49) Inflammation 1 (2%) Intestine Small, Ileum (50) (49) (49) (50) (49) Cyst 1 (2%) Inflammation 1 (2%) Liver (50) (50) (50) (50) (49) Angiectasis 3 (6%) 15 (30%) 18 (36%) 15 (30%) 21 (43%) Basophilic Focus 37 (74%) 50 (100%) 34 (68%) 33 (66%) 15 (31%) Clear Cell Focus 1 (2%) 3 (6%) 2 (4%) 6 (12%) 3 (6%) Degeneration, Cystic 5 (10%) 10 (20%) 10 (20%) 6 (12%) Eosinophilic Focus 8 (16%) 32 (64%) 34 (68%) 39 (78%) 34 (69%) Fatty Change 1 (2%) Fibrosis 1 (2%) Hematopoietic Cell Proliferation 3 (6%) 1 (2%) Hepatodiaphragmatic Nodule 5 (10%) 10 (20%) 7 (14%) 6 (12%) 5 (10%) Inflammation 25 (50%) 46 (92%) 44 (88%) 38 (76%) 46 (94%) Mixed Cell Focus 3 (6%) 30 (60%) 20 (40%) 23 (46%) 13 (27%) Necrosis 4 (8%) 4 (8%) 5 (10%) 6 (12%) 3 (6%) Thrombosis 1 (2%) 1 (2%) Vacuolization Cytoplasmic 5 (10%) 4 (8%) 6 (12%) 4 (8%) 4 (8%) Bile Duct, Cholangiofibrosis 1 (2%) 1 (2%) Bile Duct, Cyst 1 (2%) 1 (2%) 2 (4%) Bile Duct, Hyperplasia 17 (34%) 22 (44%) 20 (40%) 20 (40%) 12 (24%) Centrilobular, Degeneration 1 (2%) 1 (2%) 1 (2%) 1 (2%) Centrilobular, Hypertrophy 18 (36%) 23 (46%) 19 (38%) 26 (53%) Centrilobular, Necrosis 1 (2%) Mesentery (4) (4) (6) (3) (2) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Inflammation 1 (17%) Fat, Necrosis 3 (75%) 4 (100%) 4 (67%) 2 (67%) 2 (100%) Oral Mucosa (1) (1) Gingival, Inflammation 1 (100%) Pancreas (50) (50) (50) (50) (49) Atrophy 21 (42%) 27 (54%) 16 (32%) 22 (44%) 9 (18%) Hyperplasia 2 (4%) 1 (2%) 2 (4%) 1 (2%) Hypertrophy, Focal 1 (2%) 2 (4%) 1 (2%) Metaplasia, Hepatocyte 1 (2%) 1 (2%) Pigmentation 1 (2%) Artery, Inflammation 1 (2%) Duct, Cyst 1 (2%) Salivary Glands (50) (50) (50) (50) (48) Atrophy 1 (2%) 1 (2%) Fibrosis 1 (2%) Inflammation 1 (2%) Stomach, Forestomach (50) (50) (50) (50) (49) Edema 1 (2%) Erosion 1 (2%) Foreign Body 1 (2%) Hyperplasia 4 (8%) 1 (2%) 2 (4%) 2 (4%) 2 (4%) Inflammation 1 (2%) 1 (2%) 2 (4%) 1 (2%) Necrosis 1 (2%) Ulcer 6 (12%) 1 (2%) 3 (6%) 1 (2%) Stomach, Glandular (50) (50) (50) (50) (49) Edema 1 (2%) Erosion 2 (4%) 1 (2%) 1 (2%) 1 (2%) Inflammation 1 (2%) Mineralization 1 (2%) Ulcer 2 (4%) 1 (2%) Tooth (1) Inflammation 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) (49) Inflammation 1 (2%) 1 (2%) Heart (50) (50) (50) (50) (48) Cardiomyopathy 22 (44%) 25 (50%) 27 (54%) 28 (56%) 28 (58%) Inflammation 2 (4%) 9 (18%) 4 (8%) 1 (2%) 3 (6%) Artery, Inflammation 2 (4%) Atrium, Thrombosis 2 (4%) 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) (49) Degeneration, Cystic 6 (12%) 2 (4%) 6 (12%) 9 (18%) 3 (6%) Hematopoietic Cell Proliferation 1 (2%) Hemorrhage 1 (2%) Hyperplasia 13 (26%) 12 (24%) 17 (34%) 17 (34%) 3 (6%) Hypertrophy 3 (6%) 1 (2%) 1 (2%) 7 (14%) 5 (10%) Mineralization 1 (2%) Necrosis 1 (2%) Vacuolization Cytoplasmic 1 (2%) 2 (4%) 1 (2%) 4 (8%) 3 (6%) Adrenal Medulla (50) (50) (50) (50) (49) Cyst 1 (2%) Hyperplasia 8 (16%) 3 (6%) 4 (8%) 4 (8%) 6 (12%) Islets, Pancreatic (49) (50) (50) (50) (49) Hyperplasia 1 (2%) Parathyroid Gland (42) (44) (48) (48) (41) Hyperplasia 1 (2%) 1 (2%) Hyperplasia, Focal 1 (2%) Pituitary Gland (50) (50) (50) (49) (49) Angiectasis 1 (2%) 12 (24%) 2 (4%) 10 (20%) 6 (12%) Cyst 9 (18%) 7 (14%) 3 (6%) 3 (6%) Degeneration 1 (2%) 1 (2%) Pars Distalis, Hyperplasia 24 (48%) 27 (54%) 21 (42%) 26 (53%) 32 (65%) Pars Intermedia, Hyperplasia 1 (2%) 1 (2%) Pars Nervosa, Hyperplasia 1 (2%) Thyroid Gland (50) (50) (50) (50) (49) C-Cell, Hyperplasia 21 (42%) 29 (58%) 20 (40%) 18 (36%) 18 (37%) Follicle, Cyst 1 (2%) Follicular Cell, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (49) (46) (48) (49) (48) Hyperplasia 2 (4%) 5 (11%) 8 (17%) 4 (8%) 3 (6%) Inflammation 10 (20%) 21 (46%) 13 (27%) 11 (22%) 12 (25%) Duct, Cyst 4 (8%) 5 (11%) 2 (4%) 4 (8%) 3 (6%) Ovary (50) (50) (50) (50) (49) Atrophy 1 (2%) Cyst 5 (10%) 8 (16%) 9 (18%) 8 (16%) 6 (12%) Granulosa Cell, Hyperplasia 1 (2%) 1 (2%) Interstitial Cell, Hyperplasia 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Oviduct (1) (1) Inflammation 1 (100%) Uterus (50) (50) (50) (50) (49) Angiectasis 1 (2%) Hemorrhage 1 (2%) 1 (2%) Hyperplasia 3 (6%) 3 (6%) 3 (6%) 4 (8%) Inflammation 1 (2%) Cervix, Hypertrophy 1 (2%) Cervix, Inflammation 1 (2%) 1 (2%) Vagina (1) (1) Cyst, Squamous 1 (100%) Inflammation, Suppurative 1 (100%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) (50) Atrophy 4 (8%) 13 (26%) 13 (26%) 11 (22%) 13 (26%) Hyperplasia 19 (38%) 31 (62%) 28 (56%) 19 (38%) 23 (46%) Infiltration Cellular, Histiocyte 1 (2%) Inflammation 1 (2%) Lymph Node, Mandibular (49) (49) (50) (48) (47) Ectasia 2 (4%) 2 (4%) 1 (2%) Hyperplasia, Plasma Cell 1 (2%) 1 (2%) 1 (2%) Inflammation 1 (2%) 1 (2%) Lymph Node, Mesenteric (50) (49) (49) (50) (49) Atrophy 1 (2%) 1 (2%) 1 (2%) Ectasia 1 (2%) 1 (2%) 1 (2%) Hyperplasia, Plasma Cell 1 (2%) Spleen (50) (50) (50) (50) (49) Congestion 1 (2%) 46 (92%) 42 (84%) 44 (88%) 45 (92%) Fibrosis 1 (2%) Hematopoietic Cell Proliferation 39 (78%) 50 (100%) 47 (94%) 47 (94%) 46 (94%) Infarct 1 (2%) 1 (2%) Pigmentation 33 (66%) 45 (90%) 48 (96%) 48 (96%) 47 (96%) Capsule, Fibrosis 2 (4%) 1 (2%) 1 (2%) Lymphoid Follicle, Atrophy 1 (2%) 2 (4%) 3 (6%) Red Pulp, Depletion Cellular 1 (2%) 2 (4%) 2 (4%) Thymus (46) (48) (48) (49) (46) Atrophy 44 (96%) 48 (100%) 47 (98%) 49 (100%) 46 (100%) Artery, Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) (50) Cyst 5 (10%) 3 (6%) 4 (8%) 2 (4%) 1 (2%) Hyperplasia 23 (46%) 8 (16%) 11 (22%) 5 (10%) 5 (10%) Inflammation 1 (2%) Skin (50) (50) (50) (50) (50) Acanthosis 1 (2%) Cyst Epithelial Inclusion 1 (2%) Ulcer 1 (2%) Hair Follicle, Atrophy 1 (2%) Subcutaneous Tissue, Necrosis 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) (50) Fibrous Osteodystrophy 1 (2%) Osteopetrosis 3 (6%) 2 (4%) 3 (6%) 1 (2%) Osteoporosis 1 (2%) Maxilla, Cyst 1 (2%) Maxilla, Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) (49) Gliosis 1 (2%) Hemorrhage 1 (2%) 1 (2%) 1 (2%) Inflammation 1 (2%) 1 (2%) 1 (2%) Mineralization 1 (2%) Thrombosis 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) (48) Foreign Body 1 (2%) Inflammation 13 (26%) 18 (36%) 19 (38%) 21 (42%) 24 (50%) Pigmentation 44 (88%) 50 (100%) 48 (96%) 47 (94%) 48 (100%) Thrombosis 1 (2%) Alveolar Epithelium, Hyperplasia 3 (6%) 7 (14%) 2 (4%) 5 (10%) Nose (50) (50) (50) (50) (50) Foreign Body 4 (8%) 1 (2%) 1 (2%) 1 (2%) Inflammation 4 (8%) 2 (4%) 1 (2%) 1 (2%) 1 (2%) Nasolacrimal Duct, Inflammation 1 (2%) Respiratory Epithelium, Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (3) (2) (3) (5) Cataract 2 (100%) 3 (100%) 1 (50%) 2 (67%) 3 (60%) Degeneration 1 (50%) 2 (67%) 2 (40%) Hemorrhage 1 (20%) Inflammation 1 (50%) Cornea, Inflammation 1 (50%) Lens, Mineralization 2 (67%) 1 (50%) Retina, Degeneration 1 (50%) 3 (100%) 2 (100%) 1 (33%) 3 (60%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) (49) Accumulation, Hyaline Droplet 33 (66%) 48 (96%) 45 (90%) 44 (88%) 44 (90%) Hydronephrosis 2 (4%) 1 (2%) Infarct 1 (2%) 1 (2%) Inflammation 3 (6%) Nephropathy 39 (78%) 49 (98%) 47 (94%) 49 (98%) 49 (100%) Pigmentation 27 (54%) 50 (100%) 48 (96%) 50 (100%) 47 (96%) Medulla, Mineralization 17 (34%) 25 (50%) 27 (54%) 28 (56%) 20 (41%) Pelvis, Calculus Micro Observation Only 1 (2%) Pelvis, Inflammation 1 (2%) 1 (2%) Renal Tubule, Hyperplasia 12 (24%) 13 (26%) 15 (30%) 11 (22%) Renal Tubule, Hyperplasia, Oncocytic 2 (4%) 1 (2%) 1 (2%) Transitional Epithelium, Hyperplasia 5 (10%) 12 (24%) 3 (6%) 10 (20%) Urinary Bladder (49) (49) (49) (50) (49) Calculus Micro Observation Only 1 (2%) Inflammation 13 (27%) 16 (33%) 9 (18%) 25 (50%) 17 (35%) Transitional Epithelium, Hyperplasia 1 (2%) 1 (2%) 4 (8%) 4 (8%) Transitional Epithelium, Metaplasia, Squamous 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 60 50 50 50 60 Early Deaths Moribund Sacrifice 21 21 16 14 17 Natural Death 7 6 12 10 11 Survivors Terminal Sacrifice 21 23 22 26 22 Natural Death 1 Animals Examined Microscopically 50 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) (49) Inflammation 1 (2%) Ulcer 1 (2%) 1 (2%) Intestine Large, Colon (50) (50) (50) (50) (50) Edema 1 (2%) Inflammation 1 (2%) Mineralization 1 (2%) Parasite Metazoan 1 (2%) 1 (2%) 1 (2%) Intestine Large, Rectum (50) (50) (50) (50) (50) Mineralization 1 (2%) Parasite Metazoan 5 (10%) 7 (14%) 7 (14%) 5 (10%) 3 (6%) Intestine Large, Cecum (50) (50) (50) (50) (49) Edema 1 (2%) Inflammation 2 (4%) 2 (4%) Mineralization 1 (2%) Artery, Inflammation 1 (2%) Intestine Small, Duodenum (50) (50) (50) (50) (50) Erosion 1 (2%) 1 (2%) 1 (2%) Inflammation 2 (4%) Ulcer 2 (4%) 1 (2%) 1 (2%) Intestine Small, Jejunum (50) (50) (50) (50) (50) Inflammation 1 (2%) Ulcer 1 (2%) Intestine Small, Ileum (50) (50) (50) (50) (50) Inflammation 1 (2%) 1 (2%) 1 (2%) Liver (50) (50) (50) (50) (50) Angiectasis 6 (12%) 21 (42%) 13 (26%) 9 (18%) 9 (18%) Basophilic Focus 25 (50%) 35 (70%) 35 (70%) 32 (64%) 23 (46%) Clear Cell Focus 9 (18%) 5 (10%) 6 (12%) 8 (16%) 5 (10%) Congestion 1 (2%) Degeneration, Cystic 9 (18%) 31 (62%) 36 (72%) 28 (56%) 29 (58%) Eosinophilic Focus 9 (18%) 22 (44%) 30 (60%) 29 (58%) 20 (40%) Hematopoietic Cell Proliferation 2 (4%) 1 (2%) 3 (6%) 3 (6%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Hemorrhage 1 (2%) Hepatodiaphragmatic Nodule 5 (10%) 9 (18%) 2 (4%) 5 (10%) 4 (8%) Inflammation 13 (26%) 30 (60%) 28 (56%) 30 (60%) 27 (54%) Mineralization 1 (2%) Mixed Cell Focus 4 (8%) 12 (24%) 15 (30%) 13 (26%) 10 (20%) Necrosis 5 (10%) 5 (10%) 5 (10%) 7 (14%) 5 (10%) Pigmentation 1 (2%) Thrombosis 1 (2%) 1 (2%) 1 (2%) Vacuolization Cytoplasmic 5 (10%) 18 (36%) 23 (46%) 17 (34%) 23 (46%) Bile Duct, Cyst 1 (2%) 1 (2%) Bile Duct, Hyperplasia 48 (96%) 50 (100%) 47 (94%) 49 (98%) 47 (94%) Centrilobular, Degeneration 2 (4%) 2 (4%) 2 (4%) 1 (2%) 2 (4%) Centrilobular, Hypertrophy 4 (8%) 21 (42%) 13 (26%) 29 (58%) Centrilobular, Necrosis 1 (2%) 2 (4%) 1 (2%) Mesentery (10) (4) (6) (7) (6) Inflammation 2 (20%) Artery, Inflammation 1 (14%) Artery, Mineralization 2 (33%) Fat, Inflammation 1 (14%) Fat, Necrosis 6 (60%) 3 (75%) 2 (33%) 2 (29%) 4 (67%) Oral Mucosa (1) (2) (1) Pharyngeal, Hyperplasia 1 (50%) Pancreas (50) (50) (50) (50) (50) Atrophy 26 (52%) 30 (60%) 25 (50%) 28 (56%) 24 (48%) Hyperplasia 2 (4%) 4 (8%) 2 (4%) 2 (4%) 1 (2%) Hypertrophy, Focal 1 (2%) 6 (12%) 3 (6%) 2 (4%) 2 (4%) Inflammation 2 (4%) 2 (4%) 1 (2%) Artery, Hypertrophy 1 (2%) Artery, Inflammation 1 (2%) 1 (2%) 3 (6%) 1 (2%) 5 (10%) Artery, Mineralization 1 (2%) 3 (6%) Duct, Cyst 1 (2%) Duct, Hyperplasia 1 (2%) Salivary Glands (50) (50) (48) (50) (47) Atrophy 1 (2%) 3 (6%) 1 (2%) Hyperplasia 1 (2%) Inflammation 1 (2%) Mineralization 1 (2%) Stomach, Forestomach (50) (50) (50) (50) (50) Edema 2 (4%) 4 (8%) 2 (4%) 2 (4%) 3 (6%) Foreign Body 1 (2%) Hyperplasia 4 (8%) 11 (22%) 7 (14%) 4 (8%) 4 (8%) Inflammation 4 (8%) 2 (4%) 1 (2%) Mineralization 2 (4%) 4 (8%) Perforation 1 (2%) 1 (2%) Ulcer 3 (6%) 8 (16%) 4 (8%) 3 (6%) Stomach, Glandular (50) (50) (50) (50) (50) Erosion 2 (4%) 4 (8%) 1 (2%) 2 (4%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Fibrosis 1 (2%) 1 (2%) Hyperplasia 1 (2%) Inflammation 1 (2%) 1 (2%) 1 (2%) 1 (2%) Mineralization 2 (4%) 4 (8%) 7 (14%) 10 (20%) 10 (20%) Ulcer 3 (6%) 2 (4%) 3 (6%) 1 (2%) 3 (6%) Tooth (1) Inflammation 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) (50) Mineralization 3 (6%) 3 (6%) 4 (8%) 7 (14%) 7 (14%) Aorta, Aneurysm 1 (2%) Heart (50) (50) (50) (50) (50) Angiectasis 1 (2%) Cardiomyopathy 42 (84%) 44 (88%) 44 (88%) 43 (86%) 41 (82%) Inflammation 1 (2%) 1 (2%) 2 (4%) 1 (2%) Mineralization 1 (2%) 2 (4%) 4 (8%) 5 (10%) 5 (10%) Artery, Inflammation 1 (2%) 1 (2%) Atrium, Thrombosis 6 (12%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) (50) Accessory Adrenal Cortical Nodule 1 (2%) Degeneration, Cystic 7 (14%) 4 (8%) 3 (6%) 7 (14%) 9 (18%) Hematopoietic Cell Proliferation 1 (2%) Hemorrhage 1 (2%) 2 (4%) Hyperplasia 8 (16%) 10 (20%) 8 (16%) 13 (26%) 6 (12%) Hypertrophy 4 (8%) 1 (2%) 2 (4%) 4 (8%) 1 (2%) Necrosis 1 (2%) Pigmentation 1 (2%) Thrombosis 1 (2%) 1 (2%) Vacuolization Cytoplasmic 3 (6%) 2 (4%) 1 (2%) 4 (8%) Adrenal Medulla (50) (50) (50) (50) (50) Angiectasis 1 (2%) Hyperplasia 17 (34%) 24 (48%) 22 (44%) 20 (40%) 15 (30%) Thrombosis 1 (2%) Parathyroid Gland (49) (48) (48) (50) (45) Hyperplasia 5 (10%) 13 (27%) 19 (40%) 20 (40%) 12 (27%) Hyperplasia, Focal 1 (2%) 1 (2%) 1 (2%) 1 (2%) Inflammation 1 (2%) Pituitary Gland (50) (50) (49) (50) (50) Angiectasis 1 (2%) 1 (2%) 1 (2%) 1 (2%) Cyst 2 (4%) 3 (6%) 3 (6%) 3 (6%) 6 (12%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Hemorrhage 1 (2%) 1 (2%) Thrombosis 1 (2%) Pars Distalis, Hyperplasia 13 (26%) 26 (52%) 24 (49%) 28 (56%) 19 (38%) Pars Intermedia, Hyperplasia 1 (2%) 2 (4%) 1 (2%) Pars Nervosa, Hyperplasia 5 (10%) 1 (2%) 4 (8%) 1 (2%) Thyroid Gland (50) (50) (48) (50) (47) C-Cell, Hyperplasia 14 (28%) 22 (44%) 14 (29%) 13 (26%) 12 (26%) Follicle, Cyst 3 (6%) 2 (4%) 3 (6%) 5 (10%) 4 (9%) Follicular Cell, Hyperplasia 3 (6%) 3 (6%) 1 (2%) 1 (2%) 3 (6%) Follicular Cell, Hypertrophy 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Coagulating Gland (1) Inflammation 1 (100%) Epididymis (50) (50) (50) (50) (50) Granuloma Sperm 1 (2%) 3 (6%) 1 (2%) Inflammation 1 (2%) 1 (2%) Mineralization 1 (2%) 1 (2%) 1 (2%) Preputial Gland (50) (49) (50) (49) (50) Atrophy 1 (2%) Hyperplasia 3 (6%) 4 (8%) 3 (6%) 1 (2%) Infiltration Cellular 1 (2%) Inflammation 42 (84%) 34 (69%) 43 (86%) 37 (76%) 43 (86%) Duct, Ectasia 1 (2%) 4 (8%) 4 (8%) 4 (8%) Prostate (50) (50) (50) (50) (50) Atrophy 1 (2%) Cyst 1 (2%) 1 (2%) Hyperplasia 1 (2%) 1 (2%) 1 (2%) Inflammation 33 (66%) 37 (74%) 36 (72%) 31 (62%) 34 (68%) Metaplasia, Squamous 1 (2%) Mineralization 1 (2%) Seminal Vesicle (50) (50) (50) (49) (50) Dilatation 2 (4%) Hyperplasia 1 (2%) Inflammation 1 (2%) 1 (2%) 1 (2%) 1 (2%) Mineralization 1 (2%) 1 (2%) 2 (4%) 3 (6%) Testes (50) (50) (50) (50) (50) Atrophy 6 (12%) 10 (20%) 7 (14%) 6 (12%) 5 (10%) Thrombosis 1 (2%) Artery, Inflammation 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Interstitial Cell, Hyperplasia 27 (54%) 27 (54%) 26 (52%) 24 (48%) 26 (52%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) (50) Hemorrhage 2 (4%) 2 (4%) 1 (2%) 1 (2%) Hyperplasia 25 (50%) 28 (56%) 37 (74%) 36 (72%) 33 (66%) Myelofibrosis 1 (2%) 1 (2%) Necrosis 1 (2%) Lymph Node (8) (3) (1) (1) (2) Mediastinal, Ectasia 1 (100%) Mediastinal, Hematopoietic Cell Proliferation 1 (13%) Mediastinal, Pigmentation 1 (13%) Renal, Hyperplasia, Plasma Cell 1 (33%) Lymph Node, Mandibular (50) (50) (47) (50) (47) Atrophy 1 (2%) 1 (2%) Ectasia 8 (16%) 2 (4%) 2 (4%) 1 (2%) 4 (9%) Hyperplasia, Plasma Cell 3 (6%) 2 (4%) 1 (2%) 3 (6%) Inflammation 1 (2%) 1 (2%) Necrosis 1 (2%) Lymph Node, Mesenteric (50) (49) (50) (50) (49) Angiectasis 1 (2%) Atrophy 2 (4%) 1 (2%) 1 (2%) 2 (4%) Ectasia 3 (6%) 5 (10%) 7 (14%) 7 (14%) 7 (14%) Hemorrhage 2 (4%) 1 (2%) Necrosis 1 (2%) Spleen (50) (50) (50) (50) (50) Accessory Spleen 1 (2%) 1 (2%) 1 (2%) Angiectasis 1 (2%) Congestion 6 (12%) 35 (70%) 37 (74%) 30 (60%) 31 (62%) Fibrosis 5 (10%) 3 (6%) 2 (4%) 2 (4%) Hematopoietic Cell Proliferation 37 (74%) 45 (90%) 44 (88%) 43 (86%) 39 (78%) Hemorrhage 2 (4%) Infarct 1 (2%) Infiltration Cellular 2 (4%) 1 (2%) 1 (2%) Necrosis 1 (2%) Pigmentation 12 (24%) 36 (72%) 38 (76%) 33 (66%) 28 (56%) Capsule, Fibrosis 1 (2%) Capsule, Hyperplasia 1 (2%) Lymphoid Follicle, Atrophy 1 (2%) 2 (4%) 2 (4%) 6 (12%) Red Pulp, Depletion Cellular 3 (6%) 3 (6%) 2 (4%) 4 (8%) 2 (4%) Thymus (46) (44) (45) (46) (41) Atrophy 40 (87%) 43 (98%) 44 (98%) 46 (100%) 41 (100%) Necrosis 1 (2%) Epithelial Cell, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (45) (47) (46) (50) (47) Cyst 1 (2%) Hyperplasia 10 (22%) 21 (45%) 12 (26%) 12 (24%) 10 (21%) Mineralization 1 (2%) Duct, Hyperplasia 1 (2%) Skin (50) (50) (50) (50) (50) Cyst Epithelial Inclusion 1 (2%) 1 (2%) 1 (2%) Hemorrhage 1 (2%) Hyperplasia 1 (2%) Inflammation 2 (4%) Dermis, Fibrosis 1 (2%) 1 (2%) Hair Follicle, Atrophy 1 (2%) Subcutaneous Tissue, Inflammation, Granulomatous 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) (50) Fibrous Osteodystrophy 2 (4%) 4 (8%) 8 (16%) 11 (22%) 9 (18%) Fracture 1 (2%) Necrosis 1 (2%) Osteomalacia 13 (26%) 12 (24%) 8 (16%) 3 (6%) Osteopetrosis 1 (2%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) (50) Hemorrhage 2 (4%) 1 (2%) Inflammation, Suppurative 1 (2%) Cerebrum, Degeneration 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) (50) Cyst, Squamous 1 (2%) Foreign Body 1 (2%) 2 (4%) 1 (2%) Hemorrhage 1 (2%) 2 (4%) 2 (4%) Inflammation 11 (22%) 13 (26%) 13 (26%) 8 (16%) 14 (28%) Mineralization 1 (2%) 2 (4%) 3 (6%) 7 (14%) 6 (12%) Necrosis 1 (2%) Pigmentation 3 (6%) 6 (12%) 4 (8%) 5 (10%) 5 (10%) Thrombosis 1 (2%) 2 (4%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Alveolar Epithelium, Hyperplasia 3 (6%) 9 (18%) 9 (18%) 7 (14%) 3 (6%) Mediastinum, Inflammation 1 (2%) Mediastinum, Thrombosis 1 (2%) Nose (50) (50) (50) (50) (50) Foreign Body 4 (8%) 3 (6%) 7 (14%) 5 (10%) 6 (12%) Hemorrhage 1 (2%) Inflammation 4 (8%) 3 (6%) 8 (16%) 6 (12%) 6 (12%) Respiratory Epithelium, Inflammation 1 (2%) 3 (6%) Trachea (50) (50) (50) (50) (49) Inflammation 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (4) (5) (2) Cataract 2 (100%) 2 (50%) 4 (80%) Degeneration 1 (20%) Hemorrhage 2 (40%) Inflammation 1 (25%) 1 (50%) Mineralization 4 (80%) 1 (50%) Cornea, Inflammation 1 (25%) 1 (20%) Retina, Degeneration 2 (100%) 3 (75%) 4 (80%) 1 (50%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) (50) Accumulation, Hyaline Droplet 3 (6%) 14 (28%) 10 (20%) 16 (32%) 16 (32%) Cyst 3 (6%) 4 (8%) 9 (18%) 7 (14%) 13 (26%) Hydronephrosis 2 (4%) 2 (4%) 2 (4%) Infarct 1 (2%) 1 (2%) Inflammation 7 (14%) 5 (10%) 2 (4%) 5 (10%) 4 (8%) Mineralization, Diffuse 3 (6%) 2 (4%) 9 (18%) 8 (16%) 6 (12%) Nephropathy 50 (100%) 50 (100%) 50 (100%) 50 (100%) 50 (100%) Pigmentation 25 (50%) 31 (62%) 36 (72%) 38 (76%) 33 (66%) Thrombosis 1 (2%) Medulla, Mineralization 30 (60%) 42 (84%) 46 (92%) 47 (94%) 49 (98%) Renal Tubule, Hyperplasia 3 (6%) 7 (14%) 3 (6%) 9 (18%) 9 (18%) Renal Tubule, Hyperplasia, Oncocytic 1 (2%) 1 (2%) Transitional Epithelium, Hyperplasia 28 (56%) 45 (90%) 44 (88%) 48 (96%) 48 (96%) Urinary Bladder (50) (50) (50) (50) (49) Hemorrhage 2 (4%) 1 (2%) Inflammation 8 (16%) 8 (16%) 11 (22%) 8 (16%) 9 (18%) Serosa, Inflammation 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion NTP Experiment-Test: 88036-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC ANTHRAQUINONE Date: 02/25/99 Route: DOSED FEED Time: 11:42:20 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Transitional Epithelium, Hyperplasia 1 (2%) 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------