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

• Published in: Food and chemical toxicology 2017-01, Vol.99, p.170-181
• Main Authors: Von Tungeln, Linda S., Walker, Nigel J., Olson, Greg R., Mendoza, Maria C.B., Felton, Robert P., Thorn, Brett T., Marques, M. Matilde, Pogribny, Igor P., Doerge, Daniel R., Beland, Frederick A.
• Format: Article
• Language: English
• Subjects: Animals; Bioassay; Body Weight - drug effects; Carcinogens - administration & dosage; Carcinogens - toxicity; Cholangiocarcinoma; Cholangiofibrosis; Dose-Response Relationship, Drug; Furan; Furans - administration & dosage; Furans - toxicity; Male; Mice; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - pathology; Organ Size - drug effects; Rats; Rats, Inbred F344; Tumorigenicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2016.11.015

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. •Furan is a contaminant in many common foods.•The carcinogenicity of furan was assessed in male F344/N rats.•Exposure to furan induced malignant mesothelioma and mononuclear cell leukemia.•The most sensitive non-neoplastic lesion was cholangiofibrosis.