Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study

被引:42
|
作者
Von Tungeln, Linda S. [1 ]
Walker, Nigel J. [2 ]
Olson, Greg R. [3 ]
Mendoza, Maria C. B. [4 ]
Felton, Robert P. [4 ]
Thorn, Brett T. [4 ]
Matilde Marques, M. [5 ]
Pogribny, Igor P. [1 ]
Doerge, Daniel R. [1 ]
Beland, Frederick A. [1 ]
机构
[1] Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA
[2] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA
[3] Toxicol Pathol Associates, Jefferson, AR 72079 USA
[4] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA
[5] Univ Lisbon, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal
关键词
Furan; Tumorigenicity; Cholangiocarcinoma; Cholangiofibrosis; Rats; Bioassay; REACTIVE METABOLITE; CELL-PROLIFERATION; GENE-EXPRESSION; DRINKING-WATER; ACRYLAMIDE; TOXICITY; EXPOSURE; ADDUCTS; IDENTIFICATION; GENOTOXICITY;
D O I
10.1016/j.fct.2016.11.015
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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 nonneoplastic 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. Published by Elsevier Ltd.
引用
收藏
页码:170 / 181
页数:12
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