https://ntp.niehs.nih.gov/go/6402

Target Organs and Levels of Evidence for TR-508

Toxicology and Carcinogenesis Studies of Riddelliine (CASRN 23246-96-0) in F344/N Rats and B6C3F1 Mice (Gavage Studies)

Chemical (Study Title)
CASRN		 Peer Review Date Route/Exposure Levels Study Laboratory
Riddelliine
23246-96-0		 10/18/2001 Gavage
MR: 0 OR 1.0 MG/KG; 50/DOSE FR: 0, 0.01, 0.033, 0.1, 0.33, OR 1.0 MG/KG; 62/DOSE MM: 0, 0.1, 0.3, 1.0, OR 3.0 MG/KG; 50/DOSE FM: 0 OR 3.0 MG/KG; 50/DOSE		 Southern Research Institute

Levels of Evidence

Male Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Liver: HEMANGIOSARCOMA 0/50 43/50; ADENOMA 0/50 4/50
  • Hematopoietic System: Hematopoietic System: MONONUCLEAR CELL LEUKEMIA (ALL ORGANS) 2/50 9/50
Non-Neoplastic Lesions
  • LIVER: REGENERATIVE HEPATOCYTE HYPERPLASIA; HEPATOCYTE CYTOMEGALY; FOCAL NECROSIS; EOSINOPHILIC FOCUS; MIXED CELL FOCUS; HEMORRHAGE
  • KIDNEY: TUBULE NECROSIS
Female Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Liver: HEMANGIOSARCOMA 0/50 0/50 0/50 0/50 3/50 38/50; ADENOMA 1/50 0/50 0/50 0/50 1/50 7/50
  • Hematopoietic System: MONONUCLEAR CELL LEUKEMIA (ALL ORGANS) 12/50 8/50 13/50 18/50 18/50 14/50
Non-Neoplastic Lesions
  • LIVER: REGENERATIVE HEPATOCYTE HYPERPLASIA; HEPATOCYTE CYTOMEGALY; FOCAL NECROSIS; EOSINOPHILIC FOCUS; MIXED CELL FOCUS; CLEAR CELL FOCUS; BILE DUCT HYPERPLASIA; HEMORRHAGE
  • KIDNEY: TUBULE NECROSIS; TRANSITIONAL EPITHELIAL HYPERPLASIA
Male Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Liver: HEMANGIOSARCOMA 2/50 1/50 0/50 2/50 31/50
Non-Neoplastic Lesions
  • LIVER: HEPATOCYTE CYTOMEGALY; HEPATOCYTE KARYOMEGALY; CENTRILOBULAR HEPATOCYTE NECROSIS; FOCAL HEMORRHAGE; INCREASED SEVERITY OF FOCAL HEPATOCYTE NECROSIS
  • KIDNEY: INCREASED SEVERITY OF NEPHROPATHY; GLOMERULOSCLEROSIS; TUBULE KARYOMEGALY; TUBULE DILATATION
Other Considerations
  • LIVER: ADENOMA 16/50 18/50 14/50 5/50 0/50 CARCINOMA 23/50 21/50 19/50 20/50 3/50 COMBINED 36/50 39/50 33/50 23/50 3/50
Female Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: ALVEOLAR/BRONCHIOLAR ADENOMA 1/50 9/50 OR ALVEOLAR/BRONCHIOLAR CARCINOMA 1/50 4/50 COMBINED 2/50 13/50
Non-Neoplastic Lesions
  • LIVER: HEPATOCYTE CYTOMEGALY; HEPATOCYTE KARYOMEGALY; BILE DUCT HYPERPLASIA; MIXED CELLULAR INFILTRATION
  • KIDNEY: NEPHROPATHY; INCREASED SEVERITY OF NEPHROPATHY; GLOMERULOSCLEROSIS; TUBULE HYALINE DROPLET ACCUMULATION; TUBULE PIGMENTATION
  • LUNG: ALVEOLAR EPITHELIAL HYPERPLASIA
  • ARTERIES (CHRONIC ARTERIAL INFLAMMATION INCLUDES FOCAL): SMALL INTESTINE (DUODENUM); LARGE INTESTINE (CECUM); KIDNEY; MESENTERY; OVARY; SPLEEN; UTERUS
Other Considerations
  • LIVER: ADENOMA 9/59 0/50 OR CARCINOMA 8/49 0/50 COMBINED 16/49 0/50