NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 FINAL #1 LONG EVANS RATS Facility: Battelle Columbus Laboratory Chemical CAS #: 73-31-4 Lock Date: 02/28/03 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: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS FEMALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 10 10 10 10 10 10 Early Deaths Natural Death 1 Survivors Terminal Sacrifice 10 10 9 10 10 10 Animals Examined Microscopically 10 10 10 10 10 10 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Esophagus (10) (10) Inflammation, Chronic 1 (10%) Liver (10) (10) Clear Cell Focus 1 (10%) Inflammation, Chronic 5 (50%) 5 (50%) Pancreas (10) (10) Acinus, Atrophy 1 (10%) Tooth (4) (4) Pulp, Malformation 4 (100%) 4 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM None ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM None ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Ovary (10) (10) (10) (10) (10) (10) Angiectasis 1 (10%) 1 (10%) Cyst 2 (20%) 4 (40%) 4 (40%) 4 (40%) 6 (60%) 4 (40%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS FEMALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Mineralization 1 (10%) Uterus (10) (10) (10) (10) (10) (10) Dilatation 2 (20%) 5 (50%) 3 (30%) 5 (50%) 8 (80%) 8 (80%) Metaplasia, Squamous 1 (10%) 1 (10%) Vagina (1) Cyst 1 (100%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (10) (1) (10) Myeloid Cell, Hyperplasia 1 (100%) Lymph Node (1) Lumbar, Hyperplasia, Plasma Cell 1 (100%) Lymph Node, Mandibular (10) (1) (10) Hyperplasia, Lymphoid 1 (100%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM None ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (10) (10) Cranial Nerve, Degeneration 2 (20%) 1 (10%) Pineal Gland, Inflammation 1 (10%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (10) (10) Inflammation, Chronic 3 (30%) Metaplasia, Osseous 2 (20%) 1 (10%) Alveolar Epithelium, Hyperplasia 1 (10%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS FEMALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (10) (10) (9) (10) (10) (10) Cornea, Inflammation, Chronic 1 (10%) Iris, Synechia 1 (10%) Retina, Dysplasia 1 (10%) Harderian Gland (10) (10) (9) (10) (10) (10) Pigmentation 3 (30%) 4 (40%) 1 (11%) 4 (40%) 8 (80%) 6 (60%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (10) (10) Mineralization 6 (60%) 6 (60%) Nephropathy 5 (50%) 8 (80%) Renal Tubule, Hyperplasia 1 (10%) a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS MALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 10 10 10 10 10 10 Early Deaths Survivors Terminal Sacrifice 10 10 10 10 10 10 Animals Examined Microscopically 10 10 10 10 10 10 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Liver (10) (10) Inflammation, Chronic 5 (50%) 6 (60%) Vacuolization Cytoplasmic, Focal 1 (10%) Pancreas (10) (10) Acinus, Atrophy 1 (10%) 1 (10%) Stomach, Glandular (10) (1) (10) Hyperplasia, Focal 1 (100%) Tooth (6) (3) Pulp, Malformation 6 (100%) 3 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (10) (10) Cardiomyopathy 2 (20%) Myocardium, Infiltration Cellular, Mononuclear Cell 5 (50%) 1 (10%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM None ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (10) (1) (10) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS MALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM - CONT Atrophy 1 (100%) Preputial Gland (10) (10) Cyst 1 (10%) Inflammation, Granulomatous 1 (10%) Prostate (10) (10) Inflammation, Chronic Active 1 (10%) Testes (10) (2) (10) Bilateral, Germinal Epithelium, Degeneration 1 (50%) Germinal Epithelium, Degeneration 1 (50%) 1 (10%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Lymph Node (1) Inguinal, Inflammation, Granulomatous 1 (100%) Lymph Node, Mandibular (10) (10) Congestion 2 (20%) Hyperplasia, Lymphoid 2 (20%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM None ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (10) (10) Cranial Nerve, Degeneration 2 (20%) Cranial Nerve, Gliosis 3 (30%) 1 (10%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (10) (10) Foreign Body 1 (10%) Inflammation, Chronic 3 (30%) 2 (20%) Inflammation, Granulomatous 1 (10%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 96013-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: SUBCHRON 90-DAY MELATONIN Date: 10/27/04 Route: GAVAGE Time: 08:01:42 ____________________________________________________________________________________________________________________________________ LONG-EVANS RATS MALE 0 UG/KG 5 UG/KG 50 UG/KG 5000 50,000 200,000 UG/KG UG/KG UG/KG ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - CONT Metaplasia, Osseous 2 (20%) 1 (10%) Nose (10) (10) Inflammation, Chronic 3 (30%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Harderian Gland (10) (10) (10) (8) (10) (10) Infiltration Cellular, Lymphoid 1 (10%) Inflammation, Chronic 2 (20%) 2 (25%) Pigmentation 6 (60%) 5 (50%) 5 (63%) 4 (40%) 6 (60%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (10) (10) Mineralization 5 (50%) 5 (50%) Nephropathy 3 (30%) 5 (50%) a Number of animals examined microscopically at site and number of animals with lesion Page 7 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------