Brusick David
Regul Toxicol Pharmacol. 2008 Jul;51(2 Suppl):S37-42. doi: 10.1016/j.yrtph.2007.08.013. Epub 2007 Sep 26.
Studies demonstrating that naphthalene produces respiratory tract tumors in mice and rats raised the question of whether humans are at risk for cancer, at environmental or workplace concentrations of naphthalene. Arguments in favor of a threshold-dependent mode of action for tumor induction have been based on the facts that naphthalene does not appear to bind to DNA in vivo and that the rodent tumors occurred at high dose levels associated with substantial target site toxicity. A summary of more than 45 publications describing results for naphthalene in genetic toxicology test methods shows that 80% of the studies reported found no evidence of genotoxicity for naphthalene and that some of the studies which reported positive finding were technically unsuited to study this class of chemicals and, therefore, generated unreliable data. The remaining positive findings for naphthalene were all consistent with secondary DNA effects produced by toxicity from naphthalene alone or one of its metabolites. Based on the data reviewed in this report, it is not apparent that genetic lesions produced by naphthalene or any of its metabolites drive the tumorigenic activity.
多项研究表明，萘可在小鼠和大鼠体内诱发呼吸道肿瘤，这引发了一个问题：在环境或工作场所中萘的浓度下，人类是否面临患癌风险。支持肿瘤诱导存在阈值依赖性作用模式的观点基于以下事实：萘在体内似乎不与DNA结合，且啮齿动物肿瘤发生在与显著靶位点毒性相关的高剂量水平。对45篇以上描述萘在遗传毒理学测试方法中结果的出版物进行的总结表明，80%的研究报告未发现萘具有遗传毒性的证据，一些报告呈阳性结果的研究在技术上不适合研究此类化学物质，因此产生了不可靠的数据。萘其余的阳性结果均与仅由萘或其一种代谢物的毒性产生的继发性DNA效应一致。基于本报告中审查的数据，萘或其任何代谢物产生的基因损伤是否驱动致瘤活性并不明显。
