Institute of Toxicology, German Research Center for Environmental Health, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.
Toxicol Lett. 2011 Dec 15;207(3):286-90. doi: 10.1016/j.toxlet.2011.09.027. Epub 2011 Oct 1.
The important industrial chemical 1,3-butadiene (BD; CAS Registry Number: 106-99-0) is a potent carcinogen in B6C3F1 mice and a weak one in Sprague-Dawley rats. This difference is mainly attributed to the species-specific burden by the metabolically formed 1,2:3,4-diepoxybutane (DEB). However, only limited data exist on the DEB blood burden of rodents at BD concentrations below 100 ppm. Considering this, DEB concentrations were determined in the blood of mice and rats immediately after 6h exposures to various constant concentrations of BD of between about 1 and 1200 ppm. Immediately after its collection, blood was injected into a vial that contained perdeuterated DEB (DEB-D(6)) as internal standard. Plasma samples were prepared and treated with sodium diethyldithiocarbamate that derivatized metabolically produced DEB and DEB-D(6) to their bis(dithiocarbamoyl) esters, which were then analyzed by high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometer. DEB concentrations in blood versus BD exposure concentrations in air could be described by one-phase exponential association functions. Herewith calculated (±)-DEB concentrations in blood increased in mice from 5.4 nmol/l at 1 ppm BD to 1860 nmol/l at 1250 ppm BD and in rats from 1.2 nmol/l at 1 ppm BD to 92 nmol/l at 200 ppm BD, at which exposure concentration 91% of the calculated DEB plateau concentration in rat blood was reached. This information on the species-specific blood burden by the highly mutagenic DEB helps to explain why the carcinogenic potency of BD in rats is low compared to that in mice.
重要的工业化学品 1,3-丁二烯（BD；CAS 注册号：106-99-0）在 B6C3F1 小鼠中是一种强致癌物，在 Sprague-Dawley 大鼠中则是一种弱致癌物。这种差异主要归因于代谢形成的 1,2:3,4-二环氧丁烷（DEB）在物种特异性上的负担。然而，在 BD 浓度低于 100ppm 时，关于啮齿动物 DEB 血液负担的数据非常有限。考虑到这一点，在 1 至 1200ppm 之间的各种恒定 BD 浓度下，立即在 6h 暴露后测定了小鼠和大鼠血液中的 DEB 浓度。采集血液后，立即将其注入含有氘代 DEB（DEB-D(6)）作为内标的小瓶中。制备血浆样品并用二乙基二硫代氨基甲酸钠处理，该物质将代谢产生的 DEB 和 DEB-D(6)衍生为其双（二硫代氨基甲酰基）酯，然后通过高效液相色谱与电喷雾串联质谱联用进行分析。血液中 DEB 浓度与空气中 BD 暴露浓度之间可以用单相指数关联函数来描述。由此计算出，在 1ppm BD 时，BD 浓度为 5.4nmol/l 的小鼠血液中的（±）-DEB 浓度增加到 1250ppm BD 时的 1860nmol/l，而在 1ppm BD 时，BD 浓度为 1.2nmol/l 的大鼠血液中的（±）-DEB 浓度增加到 200ppm BD 时的 92nmol/l，此时大鼠血液中计算出的 DEB 平台浓度的 91%达到了暴露浓度。这些关于高度致突变性 DEB 在物种特异性血液负担方面的信息有助于解释为什么 BD 在大鼠中的致癌潜力低于在小鼠中的致癌潜力。
