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https://ntp.niehs.nih.gov/go/LOE-TR-558

3,3',4,4'-Tetrachloroazobenzene: Target Organs and Levels of Evidence for TR-558

Toxicology and Carcinogenesis Studies of 3,3',4,4'-Tetrachloroazobenzene (CASRN 14047-09-7) in Harlan Sprague-Dawley Rats and B6C3F1 Mice (Gavage Studies)

Chemical (Study Title)
CASRN		 Peer Review Date Route/Exposure Levels Study Laboratory
3,3',4,4'-Tetrachloroazobenzene
14047-09-7		 02/25/2009 Gavage
0, .1, .3, 1, 10, 30, OR 100 MG/KG; 10/SEX/DOSE		 Battelle Columbus Laboratory

Levels of Evidence: None



Chemical (Study Title)
CASRN		 Peer Review Date Primary Uses Route/Exposure Levels Study Laboratory
3,3',4,4'-Tetrachloroazobenzene
14047-09-7		 02/25/2009 Impurity in dichloroaniline and herbicides derived from DCA. 3,3',4,4'-TCAB is not commercially manufactured but is formed as an unwanted byproduct in the manufacture of 3,4-DCA & its herbicidal derivatives. In addition, environmental contamination by 3,3',4,4'-TCAB occurs from the degradation of chloranilide herbicides & the photolysis and biolysis of 3,4-DCA. Gavage
R: 0, 10, 30, OR 100 MG/KG AND M: 0, 3, 10, OR 30 MG/KG; 50/SEX/SPECIES/DOSE		 Battelle Columbus Laboratory

Levels of Evidence

Male Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: Cystic keratinizing epithelioma 0/50 14/50 31/50 37/50
  • Liver: Cholangiocarcinoma 0/50 4/50 4/50 6/50
  • Oral Cavity: Mucosa: Gingival squamous cell carcinoma 1/50 5/50 4/50 5/50
  • Thyroid Gland: Follicular cell adenoma 0/50 3/50 4/50 4/50
May Have Been Related
  • Thoracic Cavity: Malignant Schwannoma: 0/50 0/50 1/50 3/50
Non-Neoplastic Lesions
  • Lung: Pigmentation; alveolar epithelium metaplasia, squamous; alveolar epithelium, metaplasia, bronchiolar; alveolus infiltration cellular, histiocyte
  • Liver: Hepatocyte hypertrophy; centrilobular degeneration; necrosis; pigmentation; diffuse fatty change; oval cell hyperplasia; hematopoietic cell proliferation; eosinophilic focus; bile duct cyst; toxic hepatopathy
  • Oral Mucosa: Gingival squamous hyperplasia; gingival cystic keratinizing hyperplasia
  • Thyroid Gland: Follicular cell hypertrophy; follicular cell hyperplasia; inflammation
  • Forestomach: Epithelium, hyperplasia
  • Adrenal Cortex: Degeneration; cytoplasmic vacuolization; zona fasciculata, hyperplasia; necrosis
  • Pancreas: Atrophy; acinar cytoplasmic vacuolization; inflammation
  • Blood Vessel: Inflammation
  • Spleen: Lymphoid follicle atrophy
  • Lymph Node, Mesenteric: Pigmentation; atrophy
  • Testis: Germinal epithelial degeneration
Female Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: Cystic keratinizing epithelioma 0/50 6/50 26/49 39/49
  • Liver: Cholangiocarcinoma 1/50 1/50 1/49 3/49
  • Oral Cavity: Mucosa: Gingival squamous cell carcinoma 0/50 0/50 4/50 6/50
  • Forestomach: Squamous cell papilloma or carcinoma 0/50 1/50 0/50 4/50
May Have Been Related
  • Adrenal Gland Cortex: Ademona 1/50 1/50 3/50 4/49
Non-Neoplastic Lesions
  • Lung: Pigmentation; alveolar epithelium, metaplasia, squamous; alveolar epithelium, metaplasia, bronchiolar
  • Liver: Hepatocyte hypertrophy; centrilobular degeneration; necrosis; pigmentation; focal fatty change; diffuse fatty change; bile duct hyperplasia; oval cell hyperplasia; nodular hyperplasia; hematopoietic cell proliferation; eosinophilic focus; mixed cell focus; bile duct cyst; multinucleated hepatocyte; toxic hepatopathy; cholangiofibrosis
  • Oral Mucosa: Gingival squamous hyperplasia; gingival cystic keratinizing hyperplasia
  • Forestomach: Epithelium, hyperplasia
  • Adrenal Cortex: Cytoplasmic vacuolization; zona fasciculata, hyperplasia
  • Pancreas: Atrophy; acinar cytoplasmic vacuolization
  • Blood Vessel: Inflammation
  • Spleen: Lymphoid follicle atrophy; pigmentation
  • Lymph Node, Mesenteric: Pigmentation; atrophy
  • Nasal Cavity: Inflammation
Male Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Urinary System: Urethra: Transitional epithelial gland carcinoma 0/50 32/50 46/49 49/50
  • Lung: Alveolar/bronchiolar adenoma 5/50 16/50 12/49 6/50 alveolar/bronchiolar adenoma or carcinoma 7/50 17/50 15/49 6/50
  • Forestomach: Squamous cell carcinoma 0/50 1/50 1/49 3/50
May Have Been Related
  • Ureter: Transitional epithelial carcinoma: 0/43 0/45 1/47 0/50
Non-Neoplastic Lesions
  • Urethra: Transitional epithelial gland hyperplasia
  • Ureter: Dilatation; chronic active inflammation
  • Urinary Bladder: Transitional epithelial hyperplasia
  • Forestomach: Epithelial hyperplasia
  • Glandular Stomach: Focal epithelial hyperplasia; gland epithelium cyst; lymphoid cellular infiltration; mineralization
  • Skin: Chronic active inflammation; dermal fibrosis; epidermal hyperplasia; epidermal ulcer; hair follicle dilatation; sebaceous gland atrophy
  • Spleen: Atrophy
  • Thymus: Atrophy
  • Liver: Hematopoietic cell proliferation
  • Heart: Cardiomyopathy
  • Blood Vessel: Aorta mineralization
Female Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Skin: Fibrosarcoma 1/50 6/50 5/50 8/50 fibrosarcoma or malignant schwannoma 2/50 8/50 7/50 12/50
  • Urinary System: Urethra: Transitional epithelial gland carcinoma 0/50 0/50 0/50 2/50
  • Lung: Alveolar/bronchiolar adenoma or carcinoma 0/49 2/50 1/50 4/50 alveolar/bronchiola adenoma or carcinoma 3/49 8/50 5/50 10/50 cystic keratinizing epithelioma 0/49 0/50 0/50 2/50
  • Forestomach: Squamous cell carcinoma 0/50 1/50 1/50 4/50
May Have Been Related
  • All Organs: Malignant Lymphoma: 2/50 5/50 8/50 7/50
  • Ureter: Transitional epithelial carcinoma: 0/0 0/1 0/0 1/2
Non-Neoplastic Lesions
  • Urinary Bladder: Transitional epithelial hyperplasia
  • Lung: Chronic active inflammation
  • Forestomach: Epithelial hyperplasia
  • Glandular Stomach: Focal epithelial hyperplasia; gland epithelial cyst; lymphoid cellular infiltration
  • Skin: Chronic active inflammation; dermal fibrosis; epidermal hyperplasia epidermal ulcer; hair follicle dilatation; sebaceous gland atrophy
  • Clitoral Gland: Atrophy; duct cyst; chronic inflammation
  • Ovary: Atrophy
  • Bone Marrow: Hyperplasia
  • Spleen: Hematopoietic cell proliferation
  • Thymus: Atrophy
  • Liver: Hematopoietic cell proliferation
  • Heart: Cardiomyopathy