title: Subchronic oral toxicity study of furan in B6C3F1 Mice.
abstract: Furan is a heterocyclic organic compound formed during heat treatment for processing and preservation of various types of food. Rodent studies have previously shown that furan is a hepatocarcinogen. Those studies were conducted over a high dose range, which induced tumors at nearly 100% incidence at all doses. This ninety-day gavage study in mice was conducted to extend the dose to a lower range (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg body weight [bw] per day) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects, including those affecting clinical biochemistry, hematology, tissue morphology, and histopathology. The liver was the primary target organ with dose-dependent toxicity. Liver weights were increased at the 8.0 mg/kg bw dose in females only. Levels of the serum enzyme alanine transaminase, representative of liver damage, were increased three-fold at the highest dose. Histological changes in the liver were observed at 2.0 and 8.0 mg/kg bw in both sexes. Although clinical parameters were also altered for the kidney, these differences were not accompanied by histological changes. Based on these clinical biochemical and histological changes, a no-observed adverse effect level of 0.12 mg/kg bw per day of furan in mice is suggested.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety, Health Canada, Ottawa, Canada. Santokh.gill@hc-sc.gc.ca
authors.forename: S
authors.initials: S
authors.lastname: Gill
authors.forename: M
authors.initials: M
authors.lastname: Kavanagh
authors.forename: M
authors.initials: M
authors.lastname: Barker
authors.forename: M
authors.initials: M
authors.lastname: Weld
authors.forename: E
authors.initials: E
authors.lastname: Vavasour
authors.forename: Y
authors.initials: Y
authors.lastname: Hou
authors.forename: G M
authors.initials: GM
authors.lastname: Cooke
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D014018:Tissue Distribution; D036401:Toxicity Tests, Chronic
chemical_list: D015415:Biomarkers; D005663:Furans; C039281:furan