Filser Johannes G, Hutzler Christoph, Rampf Florian, Kessler Winfried, Faller Thomas H, Leibold Edgar, Pütz Christian, Halbach Stefan, Csanády György A
Institute of Toxicology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.
Toxicol Sci. 2008 Apr;102(2):219-31. doi: 10.1093/toxsci/kfm311. Epub 2008 Jan 4.
Propylene (PE) was not carcinogenic in long-term studies in rodents. However, its biotransformation to propylene oxide (PO) raises questions about a carcinogenic risk. PO alkylates macromolecules, is a direct mutagen, and caused tumors in rodents at high concentrations. In order to acquire knowledge on the species-specific PO concentrations in blood resulting from PE exposure, we exposed male Fischer 344/N rats in closed exposure chambers to constant PE concentrations, between 20.1 and 3000 ppm (7 h at least), and four male volunteers to mean constant PE concentrations of 9.82 and 23.4 ppm (180 min) in inhaled air. In the animal experiments, PE and PO were measured in the chamber atmosphere, PE by gas chromatography with flame ionization detection (GC/FID), PO by GC/FID or GC with mass-selective detection (GC/MSD). In the human studies, PE was measured in inhaled and exhaled air by GC/FID. PO was quantified by GC/MSD from exhaled breath collected in gasbags. Blood concentrations of PO were calculated based on the measured PO concentrations in air using the blood-to-air partition coefficients of 60 (rat) and 66 (human). In rats, PO blood concentrations ranged from 53 nmol/l at 20.1 ppm PE to 1750 nmol/l at 3000 ppm PE. In humans, mean blood concentrations of PO were 0.44 and 0.92 nmol/l at mean PE concentrations of 9.82 and 23.4 ppm, respectively. These findings should be taken into consideration when estimating the carcinogenic risk of PE to humans based on carcinogenicity studies in PE- or PO-exposed rats.
在啮齿动物的长期研究中，丙烯（PE）没有致癌性。然而，其生物转化为环氧丙烷（PO）引发了关于致癌风险的问题。PO会使大分子烷基化，是一种直接诱变剂，并且在高浓度下会在啮齿动物中引发肿瘤。为了获取有关PE暴露导致的血液中物种特异性PO浓度的知识，我们将雄性Fischer 344/N大鼠置于封闭暴露室中，使其暴露于20.1至3000 ppm的恒定PE浓度下（至少7小时），并让四名男性志愿者吸入平均恒定PE浓度为9.82和23.4 ppm的空气（180分钟）。在动物实验中，通过带有火焰离子化检测的气相色谱法（GC/FID）测定暴露室空气中的PE和PO，通过GC/FID或带有质量选择性检测的气相色谱法（GC/MSD）测定PO。在人体研究中，通过GC/FID测定吸入和呼出空气中的PE。通过GC/MSD对收集在气囊中的呼出气体进行定量分析以测定PO。使用60（大鼠）和66（人类）的血-气分配系数，根据空气中测得的PO浓度计算血液中PO的浓度。在大鼠中，PO血液浓度范围从PE浓度为20.1 ppm时的53 nmol/l到3000 ppm时的1750 nmol/l。在人类中，平均PE浓度为9.82和23.4 ppm时，PO的平均血液浓度分别为0.44和0.92 nmol/l。在基于PE或PO暴露大鼠的致癌性研究评估PE对人类的致癌风险时，应考虑这些发现。
