University Medical Center of the Johannes Gutenberg University Mainz, Institute of Occupational, Social, and Environmental Medicine, Germany.
Institute of Teachers' Health at the Institute of Occupational, Social, and Environmental Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
Toxicol Lett. 2018 Dec 1;298:81-90. doi: 10.1016/j.toxlet.2018.03.031. Epub 2018 Mar 27.
A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal exposure were analysed to investigate the suitability of selected metabolites to reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19-38 years, median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot urine samples of the volunteers, collected before exposure and during the following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2,5-dione, 1-ol, 2-ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre-exposure concentrations between <0.5 (3-one) and 82.9 μg/L (4-one), exposure increased the concentrations for all parameters except for 4-one. Median post-exposure concentrations ranged up to 840.4 μg/L (2-ol) and decreased with half-lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05) revealed weak to moderate associations of volume related metabolite excretion with external exposure for 2-one, 3-one and 2,5-dione (R = 0.332-0.753). Heptanol excretion was moderately associated with exposure (R ≥ 0.509) only after creatinine adjustment. Lacking association with external exposure impedes the use of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive indicators of exposure if creatinine correction is applied. By providing fundamental data on a panel of eight potential heptane metabolites, our study can help to promote biological monitoring of n-heptane exposure.
目前，缺乏成熟的参数和评估值会影响正己烷暴露的生物监测。本研究通过控制吸入实验，收集了尿中正己烷代谢物浓度和代谢物排泄时间过程的信息。分析了外暴露与内暴露之间的关系，以研究选定代谢物反映正己烷摄取的适用性。选择 20 名健康、不吸烟的男性（年龄 19-38 岁，中位数 25.5 岁）作为研究对象，分别暴露于 167、333 和 500ppm 的正己烷中，持续 3 小时。在暴露前和暴露后的 24 小时内，志愿者采集的尿液样本使用顶空固相微萃取-气相色谱/质谱法（HS-SPDE-GC/MS）分析正己烷-2-酮、3-酮、4-酮、2,5-二酮、1-醇、2-醇、3-醇和 4-醇。从暴露前中位数浓度<0.5（3-酮）至 82.9μg/L（4-酮），除 4-酮外，所有参数的浓度均随暴露而增加。暴露后中位数浓度高达 840.4μg/L（2-醇），暴露结束后 3 小时内半衰期下降。非参数相关分析（n=47，p<0.05）显示，体积相关代谢物排泄与 2-酮、3-酮和 2,5-二酮的外暴露呈弱至中度相关（R=0.332-0.753）。只有在肌酐调整后，正己醇的排泄才与暴露中度相关（R≥0.509）。由于与外暴露无关联，4-酮不能作为正己烷生物标志物，而 2-醇和 3-醇如果应用肌酐校正，则是暴露的敏感指标。本研究通过提供一组 8 种潜在正己烷代谢物的基础数据，有助于促进正己烷暴露的生物监测。
