TDMS Study 88138-03 Pathology Tables
NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 FINAL #1 RATS Facility: Battelle Columbus Laboratory Chemical CAS #: 119-61-9 Lock Date: 04/26/02 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: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Moribund Sacrifice 16 10 9 13 Natural Death 2 2 4 3 Survivors Terminal Sacrifice 32 38 37 34 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (50) (50) (50) (50) Inflammation 1 (2%) Periesophageal Tissue, Necrosis, Fatty 1 (2%) Intestine Large, Colon (50) (50) (50) (50) Inflammation 1 (2%) Metaplasia, Mucous 1 (2%) Parasite Metazoan 1 (2%) 3 (6%) 2 (4%) 3 (6%) Intestine Large, Rectum (50) (50) (50) (50) Parasite Metazoan 8 (16%) 8 (16%) 14 (28%) 6 (12%) Ulcer 1 (2%) Intestine Large, Cecum (50) (50) (50) (50) Inflammation 1 (2%) Mineralization 1 (2%) Intestine Small, Duodenum (50) (50) (50) (50) Hyperplasia 1 (2%) Intestine Small, Jejunum (50) (50) (50) (50) Inflammation 1 (2%) 2 (4%) Liver (50) (50) (50) (50) Angiectasis 2 (4%) 2 (4%) 5 (10%) 1 (2%) Basophilic Focus 48 (96%) 48 (96%) 41 (82%) 43 (86%) Clear Cell Focus 15 (30%) 13 (26%) 10 (20%) 10 (20%) Degeneration, Cystic 1 (2%) 3 (6%) 4 (8%) Eosinophilic Focus 6 (12%) 6 (12%) 9 (18%) Fatty Change, Diffuse 11 (22%) 8 (16%) 9 (18%) 20 (40%) Fibrosis 1 (2%) Hematopoietic Cell Proliferation 1 (2%) 6 (12%) 4 (8%) 2 (4%) Hepatodiaphragmatic Nodule 5 (10%) 6 (12%) 6 (12%) 6 (12%) Inflammation, Chronic Active 46 (92%) 38 (76%) 29 (58%) 30 (60%) Mixed Cell Focus 10 (20%) 11 (22%) 5 (10%) 5 (10%) Necrosis 12 (24%) 6 (12%) 11 (22%) 12 (24%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Bile Duct, Cyst 1 (2%) Bile Duct, Hyperplasia 10 (20%) 35 (70%) 39 (78%) 40 (80%) Hepatocyte, Centrilobular, Hypertrophy 27 (54%) 30 (60%) 33 (66%) Oval Cell, Hyperplasia 3 (6%) Mesentery (12) (18) (10) (6) Fat, Necrosis 11 (92%) 18 (100%) 10 (100%) 4 (67%) Oral Mucosa (4) (8) (4) (4) Hyperplasia, Squamous 1 (25%) Gingival, Inflammation 4 (100%) 7 (88%) 4 (100%) 4 (100%) Pancreas (50) (50) (50) (50) Basophilic Focus 1 (2%) 1 (2%) Inflammation 12 (24%) 3 (6%) 2 (4%) 6 (12%) Acinus, Atrophy 17 (34%) 10 (20%) 11 (22%) 12 (24%) Salivary Glands (50) (50) (50) (50) Atrophy 2 (4%) 1 (2%) 1 (2%) Basophilic Focus 1 (2%) 1 (2%) Inflammation 1 (2%) Stomach, Forestomach (50) (50) (50) (50) Hyperplasia, Squamous 2 (4%) 2 (4%) 2 (4%) 4 (8%) Inflammation 4 (8%) 2 (4%) 2 (4%) 3 (6%) Ulcer 1 (2%) 1 (2%) 2 (4%) Stomach, Glandular (50) (50) (50) (50) Erosion 1 (2%) 1 (2%) 1 (2%) Inflammation 2 (4%) 3 (6%) Mineralization 2 (4%) 2 (4%) Ulcer 1 (2%) 1 (2%) Epithelium, Atrophy 1 (2%) Tooth (3) (3) Inflammation 3 (100%) 2 (67%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) Mineralization 1 (2%) Heart (50) (50) (50) (50) Cardiomyopathy 46 (92%) 46 (92%) 48 (96%) 46 (92%) Atrium, Thrombosis 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Angiectasis 42 (84%) 36 (72%) 18 (36%) 24 (48%) Atrophy 1 (2%) 1 (2%) Degeneration, Cystic 3 (6%) 2 (4%) 2 (4%) Hematopoietic Cell Proliferation 3 (6%) 1 (2%) 2 (4%) 2 (4%) Hyperplasia 6 (12%) 10 (20%) 6 (12%) 6 (12%) Hypertrophy 7 (14%) 5 (10%) 5 (10%) 8 (16%) Karyomegaly 1 (2%) Necrosis 5 (10%) 7 (14%) 5 (10%) 2 (4%) Vacuolization Cytoplasmic 14 (28%) 16 (32%) 15 (30%) 20 (40%) Adrenal Medulla (50) (50) (50) (50) Hyperplasia 1 (2%) 2 (4%) Necrosis 2 (4%) Vacuolization Cytoplasmic 1 (2%) Parathyroid Gland (47) (48) (44) (48) Hyperplasia 1 (2%) 1 (2%) Pituitary Gland (50) (50) (50) (50) Angiectasis 30 (60%) 30 (60%) 23 (46%) 23 (46%) Cyst 2 (4%) 1 (2%) 1 (2%) 2 (4%) Hyperplasia 23 (46%) 24 (48%) 20 (40%) 18 (36%) Inflammation 1 (2%) Thyroid Gland (50) (50) (50) (50) C-Cell, Hyperplasia 34 (68%) 11 (22%) 13 (26%) 8 (16%) Follicle, Cyst 1 (2%) 1 (2%) 1 (2%) Follicle, Hyperplasia 2 (4%) Follicular Cell, Hyperplasia 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (50) (50) (50) Atrophy 1 (2%) Cyst 3 (6%) 2 (4%) 1 (2%) Hyperplasia 6 (12%) 1 (2%) 2 (4%) Hyperplasia, Squamous 1 (2%) Inflammation 2 (4%) 2 (4%) 2 (4%) Metaplasia, Squamous 1 (2%) Ovary (50) (50) (50) (50) Cyst 6 (12%) 13 (26%) 10 (20%) 9 (18%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Interstitial Cell, Hyperplasia 1 (2%) Uterus (50) (50) (50) (50) Angiectasis, Focal 1 (2%) Inflammation 1 (2%) Cervix, Hypertrophy 1 (2%) Endometrium, Hyperplasia, Cystic 12 (24%) 20 (40%) 20 (40%) 20 (40%) Endometrium, Hyperplasia, Adenomatous 1 (2%) 1 (2%) 1 (2%) Serosa, Inflammation, Granulomatous 2 (4%) Vagina (1) (1) Inflammation 1 (100%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) (50) (50) Inflammation, Granulomatous 1 (2%) 1 (2%) 1 (2%) 1 (2%) Myelofibrosis 2 (4%) 2 (4%) 6 (12%) Necrosis 1 (2%) 1 (2%) Erythroid Cell, Hyperplasia 8 (16%) 6 (12%) 7 (14%) 2 (4%) Myeloid Cell, Hyperplasia 11 (22%) 13 (26%) 20 (40%) 13 (26%) Lymph Node (8) (8) (11) (12) Axillary, Right, Ectasia 1 (9%) Axillary, Right, Infiltration Cellular, Plasma Cell 1 (9%) Deep Cervical, Ectasia 1 (13%) Deep Cervical, Hemorrhage 1 (13%) Deep Cervical, Infiltration Cellular, Plasma Cell 3 (38%) 2 (17%) Deep Cervical, Infiltration Cellular, Histiocyte 3 (38%) Mediastinal, Hemorrhage 2 (17%) Mediastinal, Infiltration Cellular, Plasma Cell 2 (25%) 1 (13%) 4 (36%) 2 (17%) Mediastinal, Infiltration Cellular, Histiocyte 1 (9%) 1 (8%) Pancreatic, Hemorrhage 2 (25%) Pancreatic, Infiltration Cellular, Histiocyte 3 (38%) 1 (8%) Pancreatic, Pigmentation, Hemosiderin 2 (25%) Renal, Infiltration Cellular, Histiocyte 1 (13%) 1 (8%) Renal, Pigmentation 1 (8%) Lymph Node, Mesenteric (50) (50) (50) (50) Infiltration Cellular, Plasma Cell 1 (2%) 1 (2%) 2 (4%) Infiltration Cellular, Histiocyte 50 (100%) 49 (98%) 48 (96%) 49 (98%) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Spleen (49) (50) (50) (50) Accessory Spleen 1 (2%) 1 (2%) Autolysis 2 (4%) Fibrosis 1 (2%) 1 (2%) Hematopoietic Cell Proliferation 47 (96%) 45 (90%) 40 (80%) 45 (90%) Hyperplasia, Lymphoid 1 (2%) 1 (2%) 2 (4%) Infarct 1 (2%) Inflammation, Granulomatous 1 (2%) 1 (2%) Pigmentation, Hemosiderin 48 (98%) 50 (100%) 49 (98%) 49 (98%) Lymphoid Follicle, Atrophy 5 (10%) Red Pulp, Hyperplasia 1 (2%) Thymus (50) (49) (46) (50) Atrophy 49 (98%) 48 (98%) 44 (96%) 49 (98%) Cyst 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (50) (50) (50) Atrophy 1 (2%) Galactocele 7 (14%) 3 (6%) 2 (4%) 2 (4%) Hyperplasia 3 (6%) 4 (8%) 1 (2%) 3 (6%) Inflammation 1 (2%) 1 (2%) 1 (2%) Skin (50) (50) (50) (50) Cyst Epithelial Inclusion 1 (2%) 1 (2%) Sebaceous Gland, Hyperplasia 1 (2%) Subcutaneous Tissue, Necrosis 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Fibrous Osteodystrophy 2 (4%) Skeletal Muscle (1) (1) (3) (1) Inflammation 1 (100%) 1 (100%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Gliosis 1 (2%) Hemorrhage 2 (4%) 1 (2%) 2 (4%) Hydrocephalus 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM - CONT Inflammation 1 (2%) 1 (2%) 1 (2%) Mineralization 1 (2%) Necrosis 1 (2%) 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Inflammation, Acute 2 (4%) 1 (2%) Inflammation, Granulomatous 12 (24%) 5 (10%) 9 (18%) 7 (14%) Metaplasia, Squamous 1 (2%) Alveolar Epithelium, Hyperplasia 18 (36%) 18 (36%) 13 (26%) 15 (30%) Alveolus, Infiltration Cellular, Histiocyte 50 (100%) 50 (100%) 50 (100%) 50 (100%) Interstitium, Fibrosis 1 (2%) Nose (50) (50) (50) (50) Inflammation 2 (4%) 1 (2%) 3 (6%) 1 (2%) Thrombosis 2 (4%) Trachea (50) (50) (50) (50) Inflammation 4 (8%) 2 (4%) 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (50) (50) (50) Inflammation 1 (2%) 1 (2%) 2 (4%) 1 (2%) Lens, Cataract 1 (2%) 1 (2%) 2 (4%) 2 (4%) Optic Nerve, Fibrosis 1 (2%) Retina, Degeneration 2 (4%) 2 (4%) 4 (8%) 4 (8%) Retina, Dysplasia 1 (2%) Harderian Gland (50) (50) (50) (50) Infiltration Cellular, Lymphoid 14 (28%) 10 (20%) 6 (12%) 9 (18%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Accumulation, Hyaline Droplet 2 (4%) 1 (2%) Fibrosis 1 (2%) Infarct 1 (2%) 2 (4%) 1 (2%) Inflammation, Chronic Active 1 (2%) Nephropathy 47 (94%) 49 (98%) 48 (96%) 49 (98%) Cortex, Inflammation 1 (2%) Cortex, Mineralization 2 (4%) 1 (2%) 4 (8%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ URINARY SYSTEM - CONT Medulla, Fibrosis 1 (2%) Medulla, Mineralization 43 (86%) 49 (98%) 49 (98%) 46 (92%) Pelvis, Inflammation 1 (2%) 4 (8%) 2 (4%) Pelvis, Transitional Epithelium, Hyperplasia 1 (2%) 2 (4%) 2 (4%) 4 (8%) Renal Tubule, Cyst 1 (2%) Renal Tubule, Hyperplasia 1 (2%) 1 (2%) 1 (2%) Renal Tubule, Pigmentation 1 (2%) Renal Tubule, Vacuolization Cytoplasmic 1 (2%) Urinary Bladder (50) (50) (50) (50) Hyperplasia 1 (2%) 1 (2%) Inflammation 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 Early Deaths Moribund Sacrifice 25 12 16 44 Natural Death 3 11 3 4 Survivors Terminal Sacrifice 22 27 31 2 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (50) (50) (50) (50) Erosion 1 (2%) Inflammation 1 (2%) Parasite Metazoan 1 (2%) 1 (2%) 1 (2%) Intestine Large, Rectum (50) (50) (50) (50) Parasite Metazoan 6 (12%) 6 (12%) 8 (16%) 5 (10%) Intestine Large, Cecum (50) (50) (50) (50) Erosion 1 (2%) 1 (2%) 1 (2%) Inflammation 4 (8%) Mineralization 2 (4%) Ulcer 1 (2%) Intestine Small, Duodenum (50) (50) (50) (50) Peyer's Patch, Hyperplasia, Lymphoid 1 (2%) Liver (50) (50) (50) (50) Angiectasis 1 (2%) Basophilic Focus 24 (48%) 25 (50%) 32 (64%) 19 (38%) Clear Cell Focus 19 (38%) 19 (38%) 18 (36%) Congestion 1 (2%) Degeneration, Cystic 8 (16%) 11 (22%) 20 (40%) 15 (30%) Eosinophilic Focus 5 (10%) 14 (28%) 10 (20%) 9 (18%) Fatty Change, Diffuse 22 (44%) 20 (40%) 22 (44%) 15 (30%) Hematopoietic Cell Proliferation 4 (8%) 1 (2%) 2 (4%) 4 (8%) Hepatodiaphragmatic Nodule 2 (4%) 6 (12%) 1 (2%) 1 (2%) Infarct 1 (2%) Inflammation, Chronic Active 22 (44%) 21 (42%) 35 (70%) 33 (66%) Inflammation, Granulomatous 1 (2%) 2 (4%) Mineralization 1 (2%) Mixed Cell Focus 9 (18%) 17 (34%) 22 (44%) 4 (8%) Necrosis 19 (38%) 19 (38%) 9 (18%) 14 (28%) Bile Duct, Cyst 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Bile Duct, Hyperplasia 49 (98%) 46 (92%) 48 (96%) 50 (100%) Hepatocyte, Multinucleated 1 (2%) 1 (2%) Hepatocyte, Centrilobular, Hypertrophy 17 (34%) 31 (62%) 19 (38%) Hepatocyte, Centrilobular, Necrosis 1 (2%) Vein, Inflammation 1 (2%) Mesentery (9) (12) (8) (4) Inflammation 1 (11%) 1 (13%) 1 (25%) Fat, Necrosis 7 (78%) 7 (58%) 7 (88%) 3 (75%) Oral Mucosa (8) (8) (5) (7) Gingival, Hyperplasia 1 (20%) Gingival, Inflammation 8 (100%) 6 (75%) 5 (100%) 5 (71%) Pharyngeal, Inflammation 1 (14%) Pancreas (50) (50) (50) (50) Basophilic Focus 1 (2%) Cyst 3 (6%) Inflammation 14 (28%) 16 (32%) 6 (12%) 9 (18%) Metaplasia, Hepatocyte 1 (2%) Acinus, Atrophy 20 (40%) 21 (42%) 22 (44%) 10 (20%) Acinus, Hyperplasia 1 (2%) Salivary Glands (49) (50) (50) (49) Atrophy 1 (2%) 1 (2%) 3 (6%) Inflammation 2 (4%) Stomach, Forestomach (50) (49) (49) (50) Autolysis 1 (2%) Hyperplasia, Squamous 7 (14%) 4 (8%) 10 (20%) 17 (34%) Inflammation 8 (16%) 6 (12%) 8 (16%) 12 (24%) Mineralization 1 (2%) 1 (2%) 3 (6%) Ulcer 4 (8%) 1 (2%) 8 (16%) 8 (16%) Stomach, Glandular (50) (50) (49) (50) Erosion 5 (10%) 2 (4%) 3 (6%) 3 (6%) Hyperplasia 1 (2%) Inflammation 5 (10%) 5 (10%) 4 (8%) 7 (14%) Mineralization 5 (10%) 15 (30%) Ulcer 1 (2%) 1 (2%) 4 (8%) Tooth (3) (5) (2) (3) Inflammation 1 (33%) 1 (50%) 1 (33%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Blood Vessel (50) (50) (50) (50) Inflammation 1 (2%) Mineralization 1 (2%) 1 (2%) 11 (22%) a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM - CONT Pulmonary Artery, Pulmonary Vein, Hypertrophy 1 (2%) Heart (50) (50) (50) (50) Cardiomyopathy 48 (96%) 48 (96%) 47 (94%) 49 (98%) Mineralization 2 (4%) 6 (12%) Aorta, Tunic, Media, Mineralization 1 (2%) Atrium, Thrombosis 3 (6%) 5 (10%) 2 (4%) 1 (2%) Endocardium, Hyperplasia 2 (4%) Valve, Thrombosis 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (49) (50) (50) Angiectasis 4 (8%) 4 (8%) 2 (4%) 1 (2%) Atrophy 1 (2%) Cytoplasmic Alteration 1 (2%) Degeneration, Cystic 1 (2%) Hematopoietic Cell Proliferation 5 (10%) 2 (4%) Hyperplasia 1 (2%) 4 (8%) 11 (22%) 4 (8%) Hypertrophy 8 (16%) 2 (4%) 3 (6%) 3 (6%) Necrosis 1 (2%) 4 (8%) 1 (2%) Vacuolization Cytoplasmic 27 (54%) 27 (55%) 31 (62%) 27 (54%) Adrenal Medulla (50) (49) (50) (50) Angiectasis 1 (2%) Hyperplasia 6 (12%) 8 (16%) 11 (22%) 5 (10%) Islets, Pancreatic (50) (50) (50) (50) Hyperplasia 1 (2%) Parathyroid Gland (49) (45) (48) (49) Hyperplasia 2 (4%) 1 (2%) 19 (40%) 32 (65%) Pituitary Gland (50) (50) (50) (50) Angiectasis 4 (8%) 10 (20%) 11 (22%) 3 (6%) Cyst 6 (12%) 3 (6%) 1 (2%) 5 (10%) Hyperplasia 16 (32%) 21 (42%) 12 (24%) 13 (26%) Inflammation 1 (2%) 1 (2%) Pigmentation, Hemosiderin 1 (2%) Thyroid Gland (50) (50) (50) (50) Infiltration Cellular, Mononuclear Cell 1 (2%) Ultimobranchial Cyst 2 (4%) 1 (2%) C-Cell, Hyperplasia 17 (34%) 8 (16%) 8 (16%) 5 (10%) Follicle, Cyst 1 (2%) Follicle, Degeneration 1 (2%) 2 (4%) Follicular Cell, Hyperplasia 1 (2%) 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (50) (50) (50) (50) Granuloma Sperm 1 (2%) 1 (2%) 2 (4%) Inflammation 3 (6%) 4 (8%) 1 (2%) Preputial Gland (50) (50) (50) (49) Atrophy 1 (2%) Hyperplasia 1 (2%) 1 (2%) 1 (2%) Inflammation 2 (4%) 2 (4%) 1 (2%) 1 (2%) Duct, Cyst 1 (2%) 1 (2%) Prostate (50) (50) (50) (50) Atrophy 4 (8%) 7 (14%) 8 (16%) 4 (8%) Hyperplasia 2 (4%) 3 (6%) 4 (8%) Inflammation 18 (36%) 17 (34%) 26 (52%) 26 (52%) Seminal Vesicle (50) (50) (50) (49) Atrophy 3 (6%) 7 (14%) 8 (16%) 4 (8%) Inflammation 1 (2%) 1 (2%) 1 (2%) Mineralization 4 (8%) Testes (50) (50) (50) (50) Inflammation 1 (2%) 1 (2%) Necrosis 2 (4%) Germinal Epithelium, Degeneration 6 (12%) 5 (10%) 6 (12%) 7 (14%) Interstitial Cell, Hyperplasia 15 (30%) 12 (24%) 14 (28%) 22 (44%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (49) (50) (50) Hyperplasia, Megakaryocyte 1 (2%) Inflammation, Granulomatous 1 (2%) 2 (4%) Myelofibrosis 1 (2%) 2 (4%) 2 (4%) Necrosis 1 (2%) Erythroid Cell, Hyperplasia 13 (26%) 3 (6%) 10 (20%) 10 (20%) Myeloid Cell, Hyperplasia 21 (42%) 27 (55%) 20 (40%) 14 (28%) Lymph Node (19) (20) (16) (19) Deep Cervical, Ectasia 2 (11%) 1 (5%) Deep Cervical, Infiltration Cellular, Plasma Cell 1 (5%) 2 (10%) 2 (11%) a Number of animals examined microscopically at site and number of animals with lesion Page 12 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Mediastinal, Ectasia 3 (16%) 4 (25%) 3 (16%) Mediastinal, Hemorrhage 1 (5%) 1 (6%) 2 (11%) Mediastinal, Hyperplasia 1 (6%) 2 (11%) Mediastinal, Infiltration Cellular, Plasma Cell 1 (5%) 2 (13%) 3 (16%) Mediastinal, Infiltration Cellular, Histiocyte 2 (11%) Mediastinal, Inflammation 1 (6%) Pancreatic, Ectasia 2 (13%) 2 (11%) Pancreatic, Hemorrhage 1 (6%) 1 (5%) Pancreatic, Infiltration Cellular, Histiocyte 1 (5%) 1 (5%) 2 (13%) Pancreatic, Inflammation 3 (19%) 1 (5%) Renal, Ectasia 1 (5%) Renal, Infiltration Cellular, Histiocyte 1 (5%) Lymph Node, Mandibular (5) (1) (2) Ectasia 1 (20%) Lymph Node, Mesenteric (50) (50) (50) (50) Atrophy 1 (2%) 6 (12%) Ectasia 4 (8%) 2 (4%) 5 (10%) 4 (8%) Infiltration Cellular, Histiocyte 47 (94%) 41 (82%) 48 (96%) 46 (92%) Inflammation 1 (2%) Spleen (50) (50) (50) (50) Accessory Spleen 1 (2%) Autolysis 1 (2%) Fibrosis 1 (2%) 3 (6%) 1 (2%) Hematopoietic Cell Proliferation 45 (90%) 42 (84%) 45 (90%) 41 (82%) Hemorrhage 1 (2%) 1 (2%) Hyperplasia, Lymphoid 6 (12%) 2 (4%) 9 (18%) 4 (8%) Inflammation, Granulomatous 1 (2%) 3 (6%) 7 (14%) 1 (2%) Necrosis 1 (2%) 2 (4%) 1 (2%) Pigmentation, Hemosiderin 39 (78%) 43 (86%) 44 (88%) 43 (86%) Lymphoid Follicle, Atrophy 1 (2%) 1 (2%) 2 (4%) Thymus (48) (48) (48) (48) Atrophy 44 (92%) 42 (88%) 47 (98%) 46 (96%) Ectopic Parathyroid Gland 1 (2%) 4 (8%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (48) (50) (50) Fibrosis 1 (2%) Galactocele 2 (4%) 1 (2%) Inflammation 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 13 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM - CONT Skin (50) (50) (50) (50) Hyperplasia 1 (2%) Inflammation 2 (4%) Subcutaneous Tissue, Inflammation 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Fibrous Osteodystrophy 1 (2%) 4 (8%) Osteosclerosis 1 (2%) Skeletal Muscle (2) (2) (1) Degeneration 1 (50%) 1 (50%) 1 (100%) Inflammation 1 (50%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Hemorrhage 5 (10%) 5 (10%) 2 (4%) 5 (10%) Necrosis 2 (4%) 4 (8%) Peripheral Nerve (1) Infiltration Cellular, Mononuclear Cell 1 (100%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) (50) (50) Inflammation, Acute 2 (4%) 2 (4%) 5 (10%) 7 (14%) Inflammation, Granulomatous 2 (4%) 4 (8%) 5 (10%) 2 (4%) Metaplasia, Squamous 1 (2%) Mineralization 2 (4%) 10 (20%) Necrosis 1 (2%) Thrombosis 1 (2%) 1 (2%) Alveolar Epithelium, Hyperplasia 16 (32%) 5 (10%) 13 (26%) 7 (14%) Alveolus, Infiltration Cellular, Histiocyte 46 (92%) 47 (96%) 49 (98%) 50 (100%) Bronchiole, Hyperplasia 1 (2%) 3 (6%) Interstitium, Fibrosis 2 (4%) Nose (50) (50) (50) (50) Inflammation 7 (14%) 7 (14%) 8 (16%) 9 (18%) Thrombosis 1 (2%) 2 (4%) 1 (2%) Olfactory Epithelium, Degeneration 1 (2%) Olfactory Epithelium, Metaplasia 1 (2%) 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 14 NTP Experiment-Test: 88138-03 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC BENZOPHENONE Date: 07/21/03 Route: DOSED FEED Time: 15:17:01 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 312 PPM 625 PPM 1250 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Respiratory Epithelium, Hyperplasia 1 (2%) 1 (2%) Trachea (50) (50) (50) (50) Inflammation 2 (4%) 1 (2%) 8 (16%) 3 (6%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (50) (50) (50) (50) Anterior Chamber, Inflammation 1 (2%) Ciliary Body, Inflammation 1 (2%) Cornea, Inflammation 1 (2%) Iris, Fibrosis 1 (2%) 1 (2%) Iris, Inflammation 1 (2%) 1 (2%) Lens, Cataract 2 (4%) 1 (2%) Lens, Mineralization 1 (2%) Retina, Atrophy 1 (2%) Retina, Degeneration 5 (10%) 2 (4%) 5 (10%) Harderian Gland (50) (50) (50) (50) Hyperplasia 1 (2%) 1 (2%) 1 (2%) Infiltration Cellular, Lymphoid 9 (18%) 4 (8%) 9 (18%) 3 (6%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) (50) (50) Accumulation, Hyaline Droplet 4 (8%) 1 (2%) 4 (8%) 2 (4%) Hyperplasia, Oncocytic 1 (2%) Infarct 1 (2%) 3 (6%) Nephropathy 50 (100%) 45 (90%) 50 (100%) 50 (100%) Artery, Inflammation 1 (2%) Cortex, Mineralization 1 (2%) 4 (8%) 14 (28%) Medulla, Mineralization 47 (94%) 49 (98%) 47 (94%) 49 (98%) Papilla, Transitional Epithelium, Hyperplasia 1 (2%) Pelvis, Inflammation 1 (2%) 1 (2%) Pelvis, Transitional Epithelium, Hyperplasia 1 (2%) 11 (22%) 29 (58%) 34 (68%) Renal Tubule, Cyst 1 (2%) 9 (18%) Renal Tubule, Hyperplasia 1 (2%) 5 (10%) 20 (40%) 23 (46%) Renal Tubule, Pigmentation 1 (2%) 1 (2%) 2 (4%) Urinary Bladder (50) (50) (50) (50) Calculus Gross Observation 1 (2%) 1 (2%) Inflammation 3 (6%) 2 (4%) 2 (4%) Muscularis, Degeneration 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 15 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------