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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.
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页码:170 / 181
页数:12
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