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

Food Chem Toxicol. 2017 Jan:99:170-181. doi: 10.1016/j.fct.2016.11.015. Epub 2016 Nov 18.

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.

Keywords: Bioassay; Cholangiocarcinoma; Cholangiofibrosis; Furan; Rats; Tumorigenicity.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Dose-Response Relationship, Drug
  • Furans / administration & dosage
  • Furans / toxicity*
  • Male
  • Mice
  • Neoplasms, Experimental / chemically induced*
  • Neoplasms, Experimental / pathology*
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • Furans