Gill S, Bondy G, Lefebvre D E, Becalski A, Kavanagh M, Hou Y, Turcotte A M, Barker M, Weld M, Vavasour E, Cooke G M
Toxicology Research Division, Health Products and Food Branch, Bureau of Chemical Safety, Health Canada, Ottawa, Canada.
Toxicol Pathol. 2010 Jun;38(4):619-30. doi: 10.1177/0192623310368978.
Rodent studies have shown that furan is a hepatocarcinogen. Previous studies conducted with high doses showed tumors at nearly 100% incidence at all doses. In this paper, a ninety-day gavage experiment conducted with lower doses (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg bw) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including gross changes and histopathology, clinical biochemistry, hematology, and immunotoxicology is reported. As indicated by changes in serum biomarkers, increased liver weights and gross and histological lesions, the liver is the major target organ affected by furan. There were no changes in body weights, food consumption, or histology in other organs. Some of the serum electrolyte markers, including phosphorus, were altered. There was a significant increase in serum thyroxine and triidothyronine in males. This increase was not accompanied by histological thyroid changes. Immunophenotypic analysis showed that thymic lymphocyte maturation was altered in male rats. Although altered clinical biochemistry and hematological parameters were observed at a dose of > 0.5 mg/kg bw, mild histological lesions in the liver were observed at > 0.12 mg/kg bw. Based on this finding, a furan dose of 0.03 mg/kg bw was proposed as the no-observed adverse effect level for hepatic toxicity.
啮齿动物研究表明，呋喃是一种肝致癌物。先前使用高剂量进行的研究显示，所有剂量下肿瘤发生率接近100%。本文报道了一项为期90天的灌胃实验，使用较低剂量（0.0、0.03、0.12、0.5、2.0和8.0毫克/千克体重）来确定肝毒性的未观察到有害作用水平，并描述非肿瘤性效应，包括大体变化和组织病理学、临床生物化学、血液学和免疫毒理学。正如血清生物标志物变化、肝脏重量增加以及大体和组织学病变所表明的，肝脏是受呋喃影响的主要靶器官。其他器官的体重、食物消耗量或组织学没有变化。一些血清电解质标志物，包括磷，发生了改变。雄性大鼠血清甲状腺素和三碘甲状腺原氨酸显著增加。这种增加并未伴有甲状腺组织学变化。免疫表型分析表明，雄性大鼠胸腺淋巴细胞成熟发生改变。虽然在剂量>0.5毫克/千克体重时观察到临床生物化学和血液学参数改变，但在剂量>0.12毫克/千克体重时观察到肝脏有轻度组织学病变。基于这一发现，建议将0.03毫克/千克体重的呋喃剂量作为肝毒性的未观察到有害作用水平。
