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https://ntp.niehs.nih.gov/go/850146

Target Organs and Levels of Evidence for TR-594

TR-594 Toxicology and Carcinogenesis Studies of p-Chloro-a,a,a-trifluorotoluene (CASRN 98-56-6) in Sprague Dawley Rats (Hsd:Sprague Dawley SD) and B6C3F1/N Mice (Inhalation Studies)

Chemical
CASRN
(Study Title)		 Peer Review Date Primary Uses Route/Exposure Levels Study Laboratory
p-Chloro-a,a,a-trifluorotoluene
98-56-6		 07/13/2017 Dye intermediate; solvent & dielectric fluid; intermediate for herbicides Inhalation
R: 0, 100, 300, or 1000 ppm; M: 0, 100, 200, or 400 ppm; 50/sex/species		 Battelle Northwest Laboratory


Levels of Evidence

Male Rats: Some Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Thyroid Gland: C-cell adenoma (2/50, 5/49, 3/49, 12/50)
May Have Been Related
  • Lung: alveolar/bronchiolar adenoma or carcinoma (0/50, 2/50, 0/50, 3/50)
Non-Neoplastic Lesions
  • Lung: inflammation, chronic; fibrosis; hemorrhage
  • Liver: centrilobular, hepatocyte, hypertrophy; fatty change; eosinophilic focus
  • Kidney: severity of nephropathy
  • Nasal Cavity: exudate

Female Rats: Some Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Thyroid Gland: C-cell adenoma (2/50, 8/50, 8/50, 14/50)
  • Adrenal Gland Medulla: benign pheochromocytoma (0/49, 3/50, 4/50, 6/50)
  • Uterus: adenocarcinoma (1/50, 1/50, 0/50, 5/50); stromal polyp (7/50, 9/50, 16/50, 12/50)
Non-Neoplastic Lesions
  • Lung: inflammation, chronic; fibrosis; hemorrhage
  • Liver: centrilobular, hepatocyte, hypertrophy; fatty change; mixed cell focus; clear cell focus
  • Adrenal medulla: hyperplasia
  • Uterus: endometrium, atypical hyperplasia

Male Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Liver: hepatocellular carcinoma (8/50, 19/50, 16/50, 35/50); hepatoblastoma (1/50, 1/50, 1/50, 15/50)
Non-Neoplastic Lesions
  • Lung: alveolar/bronchiolar epithelium, hyperplasia; peribronchiolar, fibrosis
  • Liver: eosinophilic focus; centrilobular, hepatocyte, hypertrophy; hepatocyte, multinucleated; hepatocyte, necrosis; intrahepatocellular erythrocytes
  • Forestomach: inflammation
  • Larynx: squamous epithelium, hyperplasia

Female Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Liver: hepatocellular adenoma (12/50, 14/50, 24/50, 34/50); hepatocellular carcinoma (7/50, 8/50, 12/50, 34/50); hepatoblastoma (0/50, 0/50, 1/50, 8/50)
  • Harderian Gland: adenoma (2/50, 6/50, 6/50, 8/50); adenoma or adenocarcinoma (2/50, 6/50, 9/50, 8/50)
Non-Neoplastic Lesions
  • Lung: alveolar/bronchiolar epithelium, hyperplasia; peribronchiolar, fibrosis
  • Liver: eosinophilic focus; centrilobular, hepatocyte, hypertrophy; hepatocyte, multinucleated; hepatocyte, necrosis
  • Forestomach: epithelium, hyperplasia