Gill S, Kavanagh M, Barker M, Weld M, Vavasour E, Hou Y, Cooke G M
Toxicology Research Division, Bureau of Chemical Safety, Health Canada, Ottawa, Canada.
Toxicol Pathol. 2011 Aug;39(5):787-94. doi: 10.1177/0192623311412980. Epub 2011 Jun 24.
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.
呋喃是在各类食品加工和保存的热处理过程中形成的一种杂环有机化合物。此前的啮齿动物研究表明，呋喃是一种肝致癌物。这些研究是在高剂量范围内进行的，所有剂量下诱发肿瘤的发生率接近100%。进行这项为期90天的小鼠灌胃研究，是为了将剂量范围扩大到较低水平（每天0.0、0.03、0.12、0.5、2.0和8.0毫克/千克体重），以确定肝毒性的未观察到有害作用水平，并描述非肿瘤效应，包括对临床生物化学、血液学、组织形态学和组织病理学的影响。肝脏是具有剂量依赖性毒性的主要靶器官。仅在8.0毫克/千克体重剂量组的雌性小鼠中肝脏重量增加。代表肝损伤的血清酶丙氨酸转氨酶水平在最高剂量下增加了三倍。在2.0和8.0毫克/千克体重剂量组的雌雄小鼠中均观察到肝脏组织学变化。虽然肾脏的临床参数也发生了改变，但这些差异并未伴随组织学变化。基于这些临床生物化学和组织学变化，建议小鼠中呋喃的未观察到有害作用水平为每天0.12毫克/千克体重。
