title: Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study.
abstract: Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Von Tungeln
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.affiliation: Toxicologic Pathology Associates, Jefferson, AR 72079, United States.
authors.forename: Greg R
authors.initials: GR
authors.lastname: Olson
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Maria C B
authors.initials: MC
authors.lastname: Mendoza
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Felton
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Thorn
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal.
authors.forename: M Matilde
authors.initials: MM
authors.lastname: Marques
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Igor P
authors.initials: IP
authors.lastname: Pogribny
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. Electronic address: frederick.beland@fda.hhs.gov.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D005663:Furans
keywords: Bioassay; Cholangiocarcinoma; Cholangiofibrosis; Furan; Rats; Tumorigenicity