Nihlén A, Sumner S C, Löf A, Johanson G
Department of Toxicology and Risk Assessment, National Institute for Working Life, SE-171 84 Solna, Sweden.
Chem Res Toxicol. 1999 Sep;12(9):822-30. doi: 10.1021/tx980274o.
After exposure to methyl tert-butyl ether (MTBE), a gasoline additive, only one metabolite [tert-butyl alcohol (TBA), <1% of dose] has been identified in human urine [Nihlén, A., et al. (1998) Toxicol. Appl. Pharmacol. 148, 274-280]. In the study presented here, metabolites of MTBE were characterized by (1)H-decoupled (13)C NMR spectroscopy in urine obtained from four volunteers experimentally exposed to 50 ppm (13)C-labeled MTBE ([1,2-(13)C(2)]MTBE) vapor (facemask) for 2 h during a light physical work load (50 W). Chemical shifts for the two adjacent (13)C-labeled carbons in [1, 2-(13)C(2)]MTBE-derived metabolites were consistent with the shifts obtained for spiked standards of alpha-hydroxyisobutyric acid (HBA) and 2-methyl-1,2-propanediol (MPD). NMR signals were not detected for labeled MTBE, TBA, or possible MTBE-derived conjugates. Quantification of HBA and MPD was performed by NMR for two urine samples (collected 20 h after exposure). One subject had 11% HBA and 1% MPD, and the other individual had 3% HBA and 1% MPD in the urine, expressed as a percentage of MTBE uptake. This indicates that HBA and MPD occur at significantly higher levels in the urine (detected by NMR) than MTBE and TBA (detected by GC). To our knowledge, this is the first characterization of MTBE metabolites, other than TBA, in humans. Further urine, blood, and expired air were collected up to 22 h after exposure, and the toxicokinetics of MTBE, TBA, and acetone were determined by GC. Low relative uptake (39%), a low level of postexposure exhalation of MTBE (17%), and low recovery of TBA in the urine (<1%) were observed. The same subjects had previously been exposed to unlabeled MTBE in a whole-body exposure study [Nihlén, A., et al. (1998) Toxicol. Appl. Pharmacol. 148, 274-280], and the toxicokinetics of MTBE and TBA in this facemask exposure did not differ from the previous whole-body chamber exposure.
接触汽油添加剂甲基叔丁基醚（MTBE）后，在人类尿液中仅鉴定出一种代谢物[叔丁醇（TBA），占剂量的<1%][尼伦，A.等人（1998年）《毒理学与应用药理学》148卷，274 - 280页]。在本研究中，通过氢去耦碳-13核磁共振光谱（(1)H - decoupled (13)C NMR spectroscopy）对MTBE的代谢物进行了表征，尿液取自四名志愿者，他们在轻度体力劳动负荷（50瓦）下通过面罩实验性接触50 ppm的碳-13标记MTBE（[1,2-(13)C(2)]MTBE）蒸汽2小时。[1,2-(13)C(2)]MTBE衍生代谢物中两个相邻的碳-13标记碳的化学位移与α-羟基异丁酸（HBA）和2-甲基-1,2-丙二醇（MPD）加标标准品获得的位移一致。未检测到标记的MTBE、TBA或可能的MTBE衍生共轭物的核磁共振信号。通过核磁共振对两个尿液样本（接触后20小时收集）中的HBA和MPD进行了定量。一名受试者尿液中的HBA为11%，MPD为1%，另一名受试者尿液中的HBA为3%，MPD为1%，均以MTBE摄入量的百分比表示。这表明尿液中（通过核磁共振检测）HBA和MPD的含量显著高于MTBE和TBA（通过气相色谱检测）。据我们所知，这是首次对人类中除TBA之外的MTBE代谢物进行表征。在接触后长达22小时内进一步收集尿液、血液和呼出气体，并通过气相色谱测定MTBE、TBA和丙酮的毒代动力学。观察到相对摄取率较低（39%）、MTBE接触后呼出水平较低（17%）以及尿液中TBA回收率较低（<1%）。这些受试者此前在一项全身暴露研究中接触过未标记的MTBE[尼伦，A.等人（1998年）《毒理学与应用药理学》148卷，274 - 280页]，此次面罩暴露中MTBE和TBA的毒代动力学与之前的全身舱室暴露没有差异。
