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https://ntp.niehs.nih.gov/go/14856

o-Nitrotoluene: Target Organs and Levels of Evidence for TR-504

Toxicology and Carcinogenesis Studies ofo-Nitrotoluene (CASRN 88-72-2) in F344/N Rats and B6C3F1 Mice (Feed Studies)

Chemical (Study Title)
CASRN		Peer Review DateRoute/Exposure LevelsStudy Laboratory
o-Nitrotoluene
88-72-2		05/03/2001Dosed-Feed
MR: 0, 625, 1250, 2000, OR 5000 PPM FR: 0, 625, 1250, OR 2000 PPM M: 0, 1250, 2500, OR 5000 PPM; 60/SEX/DOSE		Southern Research Institute

Levels of Evidence

Male Rats: Clear Evidence
TypeOrgan/Tissue (Lesion)
Neoplastic Lesions
  • Mesothelium (Abdominal Cavity/Tunica Vaginalis): MALIGNANT MESOTHELIOMA 2/60 20/60 29/60 44/60 44/60 54/60
  • Skin: (SUBCUTANEOUS) LIPOMA 0/60 4/60 13/60 13/60 10/60 12/60 FIBROMA 5/60 46/60 52/60 59/60 45/60 52/60 FIBROSARCOMA 0/60 7/60 17/60 20/60 8/60 12/60 COMBINED 5/60 47/60 55/60 59/60 47/60 53/60
  • Mammary Gland: FIBROADENOMA 0/60 7/60 10/60 2/60 13/60 20/60
  • Liver: ADENOMA 2/60 3/60 3/60 7/60 3/60 4/60 ADENOMA OR CARCINOMA 3/60 3/60 3/60 8/60 3/60 6/60 CHOLANGIOCARCINOMA 0/60 0/60 0/60 0/60 0/60 3/60 HEPATOCHOLANGIOCARCINOMA 0/60 1/60 0/60 1/60 0/60 0/60
  • Lung: ALVEOLAR/BRONCHIOLAR ADENOMA 1/60 5/60 1/60 2/60 3/60 8/60 OR ALVEOLAR/BRONCHIOLAR ADENOMA OR CARCINOMA 2/60 5/60 1/60 2/60 3/60 11/60
Non-Neoplastic Lesions
  • LIVER: EOSINOPHILIC FOCUS; MIXED CELL FOCUS; CLEAR CELL FOCUS; MIXED CELL CELLULAR INFILTRATION
  • BONE MARROW: HYPERPLASIA
  • SPLEEN: HEMATOPOIETIC CELL PROLIFERATION
  • LUNG: ALVEOLAR EPITHELIAL HYPERPLASIA
Other Considerations
  • DECREASED INCIDENCES: (MONONUCLEAR CELL LEUKEMIA) 30/60 21/60 3/60 3/60 13/60 1/60
  • DECREASED INCIDENCES: (TESTIS: INTERSTITIAL CELL ADENOMA) 55/60 53/60 51/60 46/60 50/60 27/50
Female Rats: Clear Evidence
TypeOrgan/Tissue (Lesion)
Neoplastic Lesions
  • Skin: (SUBCUTANEOUS) FIBROMA 3/60 3/60 18/60 20/60 FIBROMA OR FIBROSARCOMA 3/60 3/60 21/60 22/60
  • Mammary Gland: FIBROADENOMA 23/60 47/60 52/60 56/60
May Have Been Related
  • Liver: ADENOMA 1/60 0/59 1/60 6/60
Non-Neoplastic Lesions
  • MAMMARY GLAND: HYPERPLASIA
  • LIVER: EOSINOPHILIC FOCUS; MIXED CELL FOCUS, CLEAR CELL FOCUS; BASOPHILIC FOCUS
  • BONE MARROW: HYPERPLASIA
  • SPLEEN: HEMATOPOIETIC CELL PROLIFERATION
  • LUNG: ALVEOLAR EPITHELIAL HYPERPLASIA
  • LYMPH NODE (MANDIBULAR): LYMPHOID HYPERPLASIA
Other Considerations
  • DECREASED INCIDENCES: (MONONUCLEAR CELL LEUKEMIA) 21/60 6/60 4/60 5/60
Male Mice: Clear Evidence
TypeOrgan/Tissue (Lesion)
Neoplastic Lesions
  • Hematopoietic System: HEMANGIOSARCOMA 4/60 17/60 55/60 60/60
  • Intestines: (CECUM) CARCINOMA 0/60 12/60 9/60 0/60
Non-Neoplastic Lesions
  • LIVER: EOSINOPHILIC FOCUS; BASOPHILIC FOCUS, HEPATOCYTE NECROSIS; FOCAL HEPATOCYTE SYNCYTIAL ALTERATION
  • KIDNEY: TUBULAR PIGMENTATION
  • NASAL CAVITY: OLFACTORY EPITHELIUM DEGENERATION
Female Mice: Clear Evidence
TypeOrgan/Tissue (Lesion)
Neoplastic Lesions
  • Hematopoietic System: HEMANGIOSARCOMA 0/60 2/60 3/60 50/60
  • Intestines: (CECUM) CARCINOMA 0/60 1/60 4/60 3/60
  • Liver: ADENOMA 7/60 5/59 19/59 29/60 CARCINOMA 2/60 4/59 6/59 16/60 COMBINED 9/60 9/59 24/59 39/60
Non-Neoplastic Lesions
  • LIVER: EOSINOPHILIC FOCUS; BASOPHILIC FOCUS; HEPATOCYTE NECROSIS; FOCAL HEPATOCYTE NECROSIS; FOCAL HEPATOCYTE CYTOPLASMIC VACUOLIZATION
  • KIDNEY: TUBULAR PIGMENTATION
  • NASAL CAVITY: OLFACTORY EPITHELIUM DEGENERATION