https://ntp.niehs.nih.gov/go/LOE-TR-581

Target Organs and Levels of Evidence for TR-581

Toxicology Studies of Cobalt Metal (CASRN 7440-48-4) in F344/N Rats and B6C3F1/N Mice and Toxicology and Carcinogenesis Studies of Cobalt Metal in F344/NTac Rats and B6C3F1/N Mice (Inhalation Studies)

Chemical
CASRN
(Study Title)		 Peer Review Date Primary Uses Route/Exposure Levels Study Laboratory
Cobalt
7440-48-4		 10/29/2013 Nuclear medicine and research, industry, paints, water treatment, metallurgy (HSDB 1990). Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products. Inhalation
R&M: 0, 1.25, 2.5, or 5 mg/m3; 50/sex/species/dose		 Battelle Northwest Laboratory

Levels of Evidence

Male Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: alveolar/bronchiolar adenoma 2/50 10/50 10/50 14/50 alveolar/bronchiolar carcinoma 0/50 16/50 34/50 36/50 alveolar/bronchiolar adenoma or carcinoma 2/50 25/50 39/50 44/50
  • Adrenal Gland Medulla: benign pheochromocytoma 15/50 23/50 37/50 34/50 malignant pheochromocytoma 2/50 2/50 9/50 16/50 benign or malignant pheochromocytoma 17/50 23/50 38/50 41/50
  • Pancreas Islet Cell: adenoma or carcinoma 2/50 2/50 10/48 9/49
May Have Been Related
  • Lung: cystic keratinizing epithelioma 0/50 1/50 0/50 1/50
  • Kidney: adenoma or carcinoma (standard evaluation) 0/50 1/50 0/50 4/50 (standard and extended evaluations combined) 3/50 1/50 1/50 7/50
Non-Neoplastic Lesions
  • Lung: alveolar epithelium, hyperplasia; alveolus, proteinosis; inflammation, chronic active; bronchiole, epithelium, hyperplasia
  • Nasal Cavty: inflammation, chronic active; inflammation, suppurative; olfactory epithelium, metaplasia, respiratory; olfactory epithelium, atrophy; olfactory epithelium, hyperplasia; olfactory epithelium, hyperplasia, basal cell; olfactory epithelium, necrosis; respiratory epithelium, hyperplasia; respiratory epithelium, metaplasia, squamous; respiratory epithelium, necrosis; turbinate, atrophy
  • Testes: infarct
Female Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: alveolar/bronchiolar adenoma 2/50 7/50 9/50 13/50 alveolar/bronchiolar carcinoma 0/50 9/50 17/50 30/50 alveolar/bronchiolar adenoma or carcinoma 2/50 15/50 20/50 38/50 cystic keratinizing epithelioma 0/50 4/50 1/50 2/50
  • Adrenal Gland Medulla: benign pheochromocytoma 6/50 12/50 22/50 36/50 malignant pheochromocytoma 0/50 2/50 3/50 11/50 benign or malignant pheochromocytoma 6/50 13/50 23/50 40/50
  • Mononuclear Cell Leukemia: 16/50 29/50 28/50 27/50
May Have Been Related
  • Pancreas Islet Cell: carcinoma 1/50 0/50 0/50 3/50
Non-Neoplastic Lesions
  • Lung: alveolar epithelium, hyperplasia; alveolus, proteinosis; inflammation, chronic active; bronchiole, epithelium, hyperplasia
  • Nose: inflammation, chronic active; inflammation, suppurative; olfactory epithelium, metaplasia, respiratory; olfactory epithelium, atrophy; olfactory epithelium, hyperplasia; olfactory epithelium, hyperplasia, basal cell; respiratory epithelium, hyperplasia; respiratory epithelium, metaplasia, squamous; respiratory epithelium, necrosis; turbinate, atrophy
  • Adrenal medulla: hyperplasia
Male Mice: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions
  • Lung: alveolar/bronchiolar adenoma 7/50 11/49 15/50 3/50 alveolar/bronchiolar carcinoma 11/50 38/49 42/50 46/50 alveolar/bronchiolar adenoma or carcinoma 16/50 41/49 43/50 47/50
Non-Neoplastic Lesions
  • Lung: alveolar/bronchiolar epithelium, hyperplasia; alveolar/bronchiolar epithelium, vacuolization cytoplasmic; alveolar epithelium, hyperplasia; bronchiole, epithelium, hyperplasia; bronchiole, epithelium, erosion; proteinosis; alveolus, infiltration cellular, histiocyte; inflammation, suppurative
  • Nasal Cavity: inflammation, suppurative; olfactory epithelium, atrophy; olfactory epithelium, hyperplasia; olfactory epithelium, metaplasia, respiratory; olfactory epithelium, respiratory metaplasia, atypical; respiratory epithelium, accumulation, hyaline droplet; respiratory epithelium, vacuolization cytoplasmic; respiratory epithelium, metaplasia, squamous; turbinate, atrophy
  • Larynx: respiratory epithelium, metaplasia, squamous; respiratory epithelium, vacuolization cytoplasmic; squamous epithelium, hyperplasia
  • Trachea: epithelium, vacuolization cytoplasmic
  • Testes: germinal epithelium, degeneration
Female Mice: Clear Evidence
Type Organ/Tissue (Lesion)
May Have Been Related
  • Lung: alveolar/bronchiolar adenoma 3/49 9/50 8/50 10/50 alveolar/bronchiolar carcinoma 5/49 25/50 38/50 43/50 alveolar/bronchiolar adenoma or carcinoma 8/49 30/50 41/50 45/50
Non-Neoplastic Lesions
  • Lung: alveolar/bronchiolar epithelium, hyperplasia; alveolar/bronchiolar epithelium, vacuolization cytoplasmic; alveolar epithelium, hyperplasia; bronchiole, epithelium, hyperplasia; proteinosis; alveolus, infiltration cellular, histiocyte; inflammation, suppurative
  • Nasal Cavity: inflammation, suppurative; olfactory epithelium, atrophy; olfactory epithelium, hyperplasia; olfactory epithelium, metaplasia, respiratory; olfactory epithelium, respiratory metaplasia, atypical; respiratory epithelium, accumulation, hyaline droplet; respiratory epithelium, vacuolization cytoplasmic; respiratory epithelium, metaplasia, squamous; turbinate, atrophy
  • Larynx: respiratory epithelium, metaplasia, squamous; respiratory epithelium, vacuolization cytoplasmic; squamous epithelium, hyperplasia
  • Trachea: epithelium, vacuolization cytoplasmic