An update of the National Toxicology Program database on nasal carcinogens.
Nearly 500 long-term rodent carcinogenicity studies carried out by the National Cancer Institute and the National Toxicology Program were examined, and 12 chemicals were identified that produced nasal tumors: allyl glycidol ether, p-cresidine, 1,2-dibromo-3-chloropropane, 1,2-dibromoethane, 2,3-dibromo-1-propanol, dimethylvinyl chloride, 1,4-dioxane, 1,2-epoxybutane, iodinated glycerol, procarbazine, propylene oxide, and 2,6-xylidine. All 12 of these chemicals produced nasal tumors in rats, and 5 also produced nasal tumors in mice. Most of the nasal carcinogens (1) produced tumor increases in both sexes, (2) produced tumors at other sites as well, (3) had significantly reduced survival at doses that were carcinogenic, and (4) were genotoxic. Only 5 of the 12 nasal carcinogens were administered by inhalation. A variety of different types of nasal cavity tumors were produced, and specific tumor rates are given for those chemicals causing multiple tumor types. Increased incidences of nasal neoplasms were often accompanied by suppurative/acute inflammation, epithelial/focal hyperplasia and squamous metaplasia. However, high incidences of these nonneoplastic nasal lesions were also frequently seen in inhalation studies showing no evidence of nasal carcinogenicity, suggesting that in general nasal carcinogenesis is not associated with the magnitude of chronic toxicity observed at this site.
Haseman
J K
JK
Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. haseman@fred.niehs.nih.goo
Hailey
J R
JR
D000236:Adenoma / Q000139:chemically induced*; D000280:Administration, Inhalation; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D016208:Databases, Factual; D005260:Female; D006078:Government Programs; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D051379:Mice; D009296:Nasal Cavity / Q000187:drug effects*; D009447:Neuroblastoma / Q000139:chemically induced*; D009668:Nose Diseases / Q000139:chemically induced; D009669:Nose Neoplasms / Q000139:chemically induced*; D051381:Rats
D002273:Carcinogens