Reference SummaryDixon D, Toxicol Pathol 2008;36(3):428-39

Title

 Summary of chemically induced pulmonary lesions in the National Toxicology Program (NTP) toxicology and carcinogenesis studies.

Authors

 Dixon D; Herbert RA; Kissling GE; Brix AE; Miller RA; Maronpot RR

Journal

 Toxicol Pathol

Volume

 36

Issue

 3

Year

 2008

Pages

 428-39

Abstract

 The lung is the second most common target site of neoplasia of chemicals tested by the National Toxicology Program (NTP). Of all peer-reviewed NTP studies to date (N = 545), a total of sixty-four chemicals in sixty-six reports produced significant site-specific neoplasia in the lungs of rats and/or mice. Of the studies associated with lung tumor induction, approximately 35% were inhalation and 35% were gavage studies, with dosed-feed, dosed-water, topical, intraperitoneal, or in utero routes of chemical administration accounting for 18%, 6%, 3%, 1%, and 1% of the studies, respectively. The most commonly induced lung tumors were alveolar/bronchiolar (A/B) adenoma and/or carcinoma for both species. The most frequently observed nonneoplastic lesions included hyperplasia and inflammation in both species. The liver was the most common primary site of origin of metastatic lesions to the lungs of mice; however, skin was most often the primary site of origin of metastatic lesions to the lungs of rats. In summary, A/B adenoma and carcinoma were the most frequently diagnosed chemically induced tumors in the lungs of both rats and mice in the NTP toxicology and carcinogenesis bioassays, and hyperplasia and inflammation were the most common nonneoplastic changes observed.

Links

 J:147319 – MGI References
18441259 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified] Adipose tissue liposarcoma Skin

observed
[not specified] Adipose tissue liposarcoma
  • (see notes)
 Skin

observed
[not specified] Blood vessel hemangioma Lung

observed
[not specified] Blood vessel hemangioma
  • (see notes)
 Lung

observed
[not specified] Blood vessel hemangiosarcoma Lung

observed
[not specified] Blood vessel hemangiosarcoma
  • (see notes)
 Lung

observed
[not specified] Blood vessel hemangiosarcoma Liver

observed
[not specified] Blood vessel hemangiosarcoma
  • (see notes)
 Liver

observed
[not specified] Bone chordoma Bone

observed
[not specified] Bone chordoma
  • (see notes)
 Bone

observed
[not specified] Connective tissue - Fibroblast fibroma Lung

observed
[not specified] Connective tissue - Fibroblast fibroma
  • (see notes)
 Lung

observed
[not specified] Connective tissue - Fibroblast fibrosarcoma Lung

observed
[not specified] Connective tissue - Fibroblast fibrosarcoma
  • (see notes)
 Lung

observed
[not specified] Connective tissue - Fibroblast fibrosarcoma Skin

observed
[not specified] Connective tissue - Fibroblast fibrosarcoma
  • (see notes)
 Skin

observed
[not specified] Ear carcinoma Ear

observed
[not specified] Ear carcinoma
  • (see notes)
 Ear

observed
[not specified] Eye - Harderian gland adenocarcinoma Eye - Harderian gland

observed
[not specified] Eye - Harderian gland adenocarcinoma
  • (see notes)
 Eye - Harderian gland

observed
[not specified] Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Liver

observed
[not specified] Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • (see notes)
 Liver

observed
(C57BL/6 x C3H)F1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Lung

1.0 - 1.7
(C57BL/6 x C3H)F1 Leukocyte lymphoma Lung

4.1 - 19.2
[not specified] Liver - Bile duct cholangiocarcinoma Liver - Bile duct

observed
[not specified] Liver - Bile duct cholangiocarcinoma
  • (see notes)
 Liver - Bile duct

observed
[not specified] Liver hepatoblastoma Liver

observed
[not specified] Liver hepatoblastoma
  • (see notes)
 Liver

observed
[not specified] Liver hepatocellular carcinoma Liver

observed
[not specified] Liver hepatocellular carcinoma
  • (see notes)
 Liver

observed
[not specified] Liver hepatocellular carcinoma
  • tetranitromethane
 Liver

observed
[not specified] Liver hepatocholangiocarcinoma Liver

observed
[not specified] Liver hepatocholangiocarcinoma
  • (see notes)
 Liver

observed
[not specified] Lung - Alveolus hyperplasia - alveolar Lung - Alveolus

observed
[not specified] Lung - Bronchiole adenoma
  • (see notes)
 Lung - Bronchiole

low
[not specified] Lung - Bronchiole adenoma Lung - Bronchiole

0
[not specified] Lung - Bronchiole carcinoma
  • (see notes)
 Lung - Bronchiole

low
[not specified] Lung - Bronchiole carcinoma Lung - Bronchiole

0
[not specified] Lung adenocarcinoma
  • (see notes)
 Lung

observed
(C57BL/6 x C3H)F1 Lung adenoma Lung

4.6 - 17.4
[not specified] Lung adenoma
  • acrylonitrile
 Lung

0 - observed
[not specified] Lung adenoma
  • 1-amino-2,4-dibromoanthraquinone
 Lung

0 - observed
[not specified] Lung adenoma
  • benzene
 Lung

observed
[not specified] Lung adenoma
  • 2,2-bis(Bromomethyl)-1,3-propanediol
 Lung

observed
[not specified] Lung adenoma
  • bis(2-chloro-1-methylethyl) ether
 Lung

observed
[not specified] Lung adenoma
  • bromoethane (ethyl bromide)
 Lung

0
[not specified] Lung adenoma
  • 1,3-butadiene
 Lung

observed
[not specified] Lung adenoma
  • chlorendic acid
 Lung

0
[not specified] Lung adenoma
  • chloroprene
 Lung

observed
[not specified] Lung adenoma
  • cobalt sulfate heptahydrate
 Lung

observed
[not specified] Lung adenoma
  • coumarin
 Lung

observed
[not specified] Lung adenoma
  • dibromoacetic acid
 Lung

observed
[not specified] Lung adenoma
  • 1,2-dibromo-3-chloropropane
 Lung

observed
[not specified] Lung adenoma
  • 1,2-dibromoethane
 Lung

observed
[not specified] Lung adenoma
  • 2,3-dibromo-1-propanol
 Lung

observed
[not specified] Lung adenoma
  • 1,2-dichloroethane
 Lung

observed
[not specified] Lung adenoma
  • 1,3-dichloropropene (telone II)
 Lung

observed
[not specified] Lung adenoma
  • dimethyl hydrogen phosphite
 Lung

0
[not specified] Lung adenoma
  • 1,2-epoxybutane
 Lung

0
[not specified] Lung adenoma
  • estradiol mustard
 Lung

observed
[not specified] Lung adenoma
  • ethylbenzene
 Lung

0 - observed
[not specified] Lung adenoma
  • ethylene oxide
 Lung

observed
[not specified] Lung adenoma
  • gallium arsenide
 Lung

0
[not specified] Lung adenoma
  • glycidol
 Lung

0 - observed
[not specified] Lung adenoma
  • HC Blue 1
 Lung

0
[not specified] Lung adenoma
  • indium phosphide
 Lung

observed
[not specified] Lung adenoma
  • isobutyl nitrite
 Lung

observed
[not specified] Lung adenoma
  • methylene chloride (MC)
 Lung

observed
[not specified] Lung adenoma
  • 4-methylimidazole
 Lung

observed
[not specified] Lung adenoma
  • N-methyloacrylamide
 Lung

observed
[not specified] Lung adenoma
  • molybdenum trioxide
 Lung

observed
[not specified] Lung adenoma
  • naphthalene
 Lung

0 - observed
[not specified] Lung adenoma
  • 1,5-naphthalenediamine
 Lung

0 - observed
[not specified] Lung adenoma
  • nickel (II) oxide
 Lung

0
[not specified] Lung adenoma
  • nickel subsulfide
 Lung

0
[not specified] Lung adenoma
  • 5-nitroacenaphthene
 Lung

0
[not specified] Lung adenoma
  • nitromethane
 Lung

observed
[not specified] Lung adenoma
  • O-nitrotoluene
 Lung

0
[not specified] Lung adenoma
  • ozone
 Lung

0 - observed
[not specified] Lung adenoma
  • phenesterin
 Lung

0
[not specified] Lung adenoma
  • procarbazine hydrochloride
 Lung

observed
[not specified] Lung adenoma
  • riddelliine
 Lung

0 - observed
[not specified] Lung adenoma
  • selenium sulfide
 Lung

0 - observed
[not specified] Lung adenoma
  • sulfallate
 Lung

0 - observed
[not specified] Lung adenoma
  • talc
 Lung

0
[not specified] Lung adenoma
  • tetranitromethane
 Lung

observed
[not specified] Lung adenoma
  • trifluralin
 Lung

0 - observed
[not specified] Lung adenoma
  • 2,4,5,-trimethylaniline
 Lung

0
[not specified] Lung adenoma
  • TRIS(2,3-dibromopropyl) phosphate
 Lung

observed
[not specified] Lung adenoma
  • urethane (ethyl carbamate)
 Lung

observed
[not specified] Lung adenoma
  • vanadium pentoxide
 Lung

observed
[not specified] Lung adenoma
  • 4-vinyl-1-cyclohexene diepoxide
 Lung

0 - observed
[not specified] Lung adenoma
  • benzofuran
 Lung

observed
(C57BL/6 x C3H)F1 Lung adenoma
  • beta-myrcene
 Lung

observed
(C57BL/6 x C3H)F1 Lung carcinoma Lung

2.8 - 10.3
[not specified] Lung carcinoma
  • acrylonitrile
 Lung

0 - observed
[not specified] Lung carcinoma
  • 1-amino-2,4-dibromoanthraquinone
 Lung

0 - observed
[not specified] Lung carcinoma
  • benzene
 Lung

observed
[not specified] Lung carcinoma
  • 2,2-bis(Bromomethyl)-1,3-propanediol
 Lung

observed
[not specified] Lung carcinoma
  • bis(2-chloro-1-methylethyl) ether
 Lung

observed
[not specified] Lung carcinoma
  • bromoethane (ethyl bromide)
 Lung

0
[not specified] Lung carcinoma
  • 1,3-butadiene
 Lung

observed
[not specified] Lung carcinoma
  • chlorendic acid
 Lung

0
[not specified] Lung carcinoma
  • chloroprene
 Lung

observed
[not specified] Lung carcinoma
  • cobalt sulfate heptahydrate
 Lung

observed
[not specified] Lung carcinoma
  • coumarin
 Lung

observed
[not specified] Lung carcinoma
  • dibromoacetic acid
 Lung

observed
[not specified] Lung carcinoma
  • 1,2-dibromo-3-chloropropane
 Lung

observed
[not specified] Lung carcinoma
  • 1,2-dibromoethane
 Lung

observed
[not specified] Lung carcinoma
  • 2,3-dibromo-1-propanol
 Lung

observed
[not specified] Lung carcinoma
  • 1,2-dichloroethane
 Lung

0
[not specified] Lung carcinoma
  • 1,3-dichloropropene (telone II)
 Lung

observed
[not specified] Lung carcinoma
  • dimethyl hydrogen phosphite
 Lung

0
[not specified] Lung carcinoma
  • 1,2-epoxybutane
 Lung

0
[not specified] Lung carcinoma
  • estradiol mustard
 Lung

observed
[not specified] Lung carcinoma
  • ethylbenzene
 Lung

0 - observed
[not specified] Lung carcinoma
  • ethylene oxide
 Lung

observed
[not specified] Lung carcinoma
  • gallium arsenide
 Lung

0
[not specified] Lung carcinoma
  • glycidol
 Lung

0 - observed
[not specified] Lung carcinoma
  • HC Blue 1
 Lung

0
[not specified] Lung carcinoma
  • indium phosphide
 Lung

observed
[not specified] Lung carcinoma
  • isobutyl nitrite
 Lung

observed
[not specified] Lung carcinoma
  • methylene chloride (MC)
 Lung

observed
[not specified] Lung carcinoma
  • 4-methylimidazole
 Lung

observed
[not specified] Lung carcinoma
  • N-methyloacrylamide
 Lung

observed
[not specified] Lung carcinoma
  • molybdenum trioxide
 Lung

observed
[not specified] Lung carcinoma
  • naphthalene
 Lung

0
[not specified] Lung carcinoma
  • 1,5-naphthalenediamine
 Lung

0 - observed
[not specified] Lung carcinoma
  • nickel (II) oxide
 Lung

0
[not specified] Lung carcinoma
  • nickel subsulfide
 Lung

0
[not specified] Lung carcinoma
  • 5-nitroacenaphthene
 Lung

0
[not specified] Lung carcinoma
  • nitromethane
 Lung

observed
[not specified] Lung carcinoma
  • O-nitrotoluene
 Lung

0
[not specified] Lung carcinoma
  • ozone
 Lung

0 - observed
[not specified] Lung carcinoma
  • phenesterin
 Lung

observed
[not specified] Lung carcinoma
  • procarbazine hydrochloride
 Lung

observed
[not specified] Lung carcinoma
  • riddelliine
 Lung

0 - observed
[not specified] Lung carcinoma
  • selenium sulfide
 Lung

0 - observed
[not specified] Lung carcinoma
  • sulfallate
 Lung

0 - observed
[not specified] Lung carcinoma
  • talc
 Lung

0
[not specified] Lung carcinoma
  • tetranitromethane
 Lung

observed
[not specified] Lung carcinoma
  • trifluralin
 Lung

0 - observed
[not specified] Lung carcinoma
  • 2,4,5,-trimethylaniline
 Lung

0
[not specified] Lung carcinoma
  • TRIS(2,3-dibromopropyl) phosphate
 Lung

observed
[not specified] Lung carcinoma
  • urethane (ethyl carbamate)
 Lung

observed
[not specified] Lung carcinoma
  • vanadium pentoxide
 Lung

observed
[not specified] Lung carcinoma
  • 4-vinyl-1-cyclohexene diepoxide
 Lung

0 - observed
[not specified] Lung carcinoma
  • benzofuran
 Lung

observed
(C57BL/6 x C3H)F1 Lung carcinoma
  • 1,3-butadiene
 Lung

observed
(C57BL/6 x C3H)F1 Lung carcinoma
  • 1,2-dibromoethane
 Lung

observed
(C57BL/6 x C3H)F1 Lung squamous cell carcinoma Lung

0
(C57BL/6 x C3H)F1 Lung squamous cell carcinoma
  • (see notes)
 Lung

0
[not specified] Lung tumor Lung

low
[not specified] Lung tumor
  • (see notes)
 Lung

low
(C57BL/6 x C3H)F1 Lung tumor Lung

0
[not specified] Mammary gland adenocarcinoma Mammary gland

observed
[not specified] Mammary gland adenocarcinoma
  • (see notes)
 Mammary gland

observed
[not specified] Mesodermal cell/mesoblast sarcoma Lung

observed
[not specified] Mesodermal cell/mesoblast sarcoma
  • (see notes)
 Lung

observed
[not specified] Mesodermal cell/mesoblast sarcoma Skin

observed
[not specified] Mesodermal cell/mesoblast sarcoma
  • (see notes)
 Skin

observed
(C57BL/6 x C3H)F1 Mesothelium mesothelioma Lung

low
(C57BL/6 x C3H)F1 Mesothelium mesothelioma
  • (see notes)
 Lung

very low
[not specified] Muscle - Smooth leiomyosarcoma Lung

observed
[not specified] Muscle - Smooth leiomyosarcoma
  • (see notes)
 Lung

observed
[not specified] Skin squamous cell carcinoma Skin

observed
[not specified] Skin squamous cell carcinoma
  • (see notes)
 Skin

observed
[not specified] (Unspecified organ) histiocytoma - fibrous - malignant Liver

observed
[not specified] (Unspecified organ) histiocytoma - fibrous - malignant
  • (see notes)
 Liver

observed
[not specified] (Unspecified organ) histiocytoma - fibrous - malignant Skin

observed
[not specified] (Unspecified organ) histiocytoma - fibrous - malignant
  • (see notes)
 Skin

observed