甲基叔丁基醚 | 1634-04-4

• 物质功能分类: 有机原料 - 醚类化合物及其衍生物 - 醚、醚醇
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 甲基叔丁基醚
• 中文别名: 2-甲氧基-2-甲基丙烷；2-甲氧基-甲基丙烷；叔丁基甲基醚；叔丁基甲基醚MtBE；叔丁基甲醚；MTBE；甲基叔丁醚
• 英文名称: tert-butyl methyl ether
• 英文别名: methyl tert - butyl ether；t-butyl methyl ether；MTBE；2-methoxy-2-methylpropane；TBME；methyl t-butyl ether；methyl tertiary-butyl ether；tert‐butyl methyl ether；Methyl tert-butyl ether
• CAS: 1634-04-4
• 化学式: C₅H₁₂O
• 分子量: 88.1497
• InChiKey: BZLVMXJERCGZMT-UHFFFAOYSA-N

物化性质

• 熔点：
  -110 °C
• 沸点：
  55-56 °C(lit.)
• 密度：
  0.7404
• 蒸气密度：
  3.1 (vs air)
• 闪点：
  -27 °F
• 溶解度：
  水中的溶解度为42克/升
• 最大波长(λmax)：
  λ: 210 nm Amax: 1.0λ: 225 nm Amax: 0.50λ: 250 nm Amax: 0.10λ: 300-400 nm Amax: 0.005
• 介电常数：
  4.5
• 暴露限值：
  ACGIH: TWA 50 ppm
• LogP：
  1.06 at 20℃
• 物理描述：
  Methyl tert-butyl ether appears as a colorless liquid with a distinctive anesthetic-like odor. Vapors are heavier than air and narcotic. Boiling point 131°F. Flash point 18°F. Less dense than water and miscible in water. Used as a octane booster in gasoline.
• 颜色/状态：
  Liquid
• 气味：
  Terpene-like odor
• 蒸汽密度：
  Relative vapor density (air = 1): 3.0
• 蒸汽压力：
  250 mm Hg at 25 °C /extrapolated/
• 亨利常数：
  5.87e-04 atm-m3/mole
• 大气OH速率常数：
  2.94e-12 cm3/molecule*sec
• 稳定性/保质期：
  1. **稳定性**：稳定。 2. **禁配物**：强氧化剂。 3. **聚合危害**：不聚合。
• 自燃温度：
  435 °C
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 燃烧热：
  101,000 btu/gal at 25 °C (804 kcal/mole)
• 汽化热：
  145 btu/lb at 55 °C (7 kcal/mole)
• 折光率：
  Index of refraction = 1.3664 at 25 °C/D
• 解离常数：
  pKa = -3.70
• 保留指数：
  570.12;562.7;563.7;568;562;566;566;567;563;568.3;556;570;554;556.1;561.3;560;556;556;556;558;560

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

研究了人类和 rats 吸入 4 和 40 ppm 的甲基叔丁基醚 (MTBE)、乙基叔丁基醚 (ETBE) 和叔戊基甲基醚 (TAME) 后，这些醚的生物转化情况，以及人类摄入含 5 和 15 毫克 MTBE 和 TAME 的水后，这些醚的生物转化情况。发现叔丁醇（TBA）、TBA 的结合物、2-甲基-1,2-丙二醇和 2-羟基异丁酸是 MTBE 和 ETBE 的代谢物。叔戊醇（TAA）、自由的和葡萄糖苷化的 2-甲基-2,3-丁二醇（TAA 的葡萄糖苷酸）、2-羟基-2-甲基丁酸和 3-羟基-3-甲基丁酸是 TAME 的代谢物。吸入后，MTBE、ETBE 和 TAME 在大鼠和人类中迅速被吸收；在暴露结束后，通过呼出和生物转化为尿液代谢物，醚在血液中的清除半衰期在大鼠和人类中均小于 7 小时。吸入暴露后，MTBE 和 ETBE 在人类和大鼠中的生物转化相似。2-羟基异丁酸作为主要产品在尿液中回收。MTBE 和 ETBE 的所有尿液代谢物都在半衰期小于 20 小时内排出。TAME 在大鼠和人类中的生物转化在性质上是相似的，但代谢途径不同。在人类中，2-甲基-2,3-丁二醇、2-羟基-2-甲基丁酸和 3-羟基-3-甲基丁酸作为主要的尿液产品回收。然而，在大鼠中，2-甲基-2,3-丁二醇及其葡萄糖苷酸是尿液中回收的主要 TAME 代谢物。摄入 MTBE 和 TAME 后，这两种化合物从胃肠道迅速吸收。这些醚的肝脏首过代谢并未观察到，并且给药剂量的显著部分被转移到血液中并通过呼出清除。MTBE 和 TAME 的代谢途径和排泄动力学在摄入和吸入暴露后是相同的。...

The biotransformation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of MTBE, ETBE, and TAME, respectively, for 4 hours, and the biotransformation of MTBE and TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. tert-Butyl alcohol (TBA), a TBA conjugate, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate were found to be metabolites of MTBE and ETBE. tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation, MTBE, ETBE, and TAME were rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. Biotransformation of MTBE and ETBE was similar in humans and rats after inhalation exposure. 2-Hydroxyisobutyrate was recovered as a major product in urine. All metabolites of MTBE and ETBE excreted with urine were eliminated with half-times of less than 20 hours. Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion of MTBE and TAME, both compounds were rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism of these ethers was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for MTBE and TAME and kinetics of excretion were identical after ingestion and inhalation exposures. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲基叔丁基醚（MTBE）在大鼠体内主要代谢成叔丁醇。通过吸入、口服、皮肤和静脉途径暴露于(14)C-MTBE的Fischer 344大鼠的代谢情况已被研究。无论通过哪种途径暴露，Fischer 344大鼠的呼吸和尿液代谢物大体相似，表明代谢途径与暴露途径无关。通过所有途径暴露后，大部分呼出的放射性物质是由于未改变的MTBE和叔丁醇，以MTBE为主。只检测到少量(14)C二氧化碳。MTBE和叔丁醇通常不在尿液中发现，但分离出四种尿液代谢物，其中两种被鉴定为α-羟基异丁酸和2-甲基-1,2-丙二醇。另外两种代谢物未被鉴定。在吸入和口服暴露后，低剂量大鼠呼出的叔丁醇比例高于高剂量大鼠。在吸入实验中，大鼠在400或8000 ppm的(14)C-MTBE中暴露6小时，或每天在400 ppm的无标记MTBE中暴露6小时，连续14天，然后在第15天暴露于400 ppm的(14)C-MTBE。在单次和重复低浓度暴露后3小时，叔丁醇分别占呼出气体中回收到的放射性活性的25%和30%。在较高浓度下暴露6小时，作为叔丁醇回收的份额较低（7-10%）。在暴露后3-6小时，在单次和重复暴露实验中，低剂量的叔丁醇代表72-80%的放射性，高剂量的叔丁醇代表43-54%。将(14)C-MTBE静脉注射到Fischer 344大鼠的结果与吸入、口服和皮肤途径的结果相似。在Charles River CD（Sprague-Dawley）大鼠中单次腹腔注射232 mg/kg的(14)C-MTBE后，血液、组织、呼出气体、尿液和粪便在不同时间点取样，直至48小时。在6小时时，大约92%的放射性剂量通过呼出气体排出，其中99.1%是未改变的MTBE。平均7.38%的给药剂量以放射性二氧化碳形式呼出。尿液分析显示，放射性甲酸占尿液中放射性活性的96.6%。尿液中剩余的放射性活性被认为是放射性甲醇和甲醛。甲醇和甲酸也在血浆、肾脏和肝脏中检测到。尿液中没有发现叔丁醇。使用对照组和苯巴比妥预处理大鼠（未指明品种）的肝脏微粒体研究了MTBE代谢成甲醛的过程。苯巴比妥预处理大约使MTBE形成甲醛的量加倍。甲醛的进一步代谢产生甲醇和/或甲酸；可能的酶和辅因子是醇脱氢酶和NADH用于甲醇的形成，以及醛脱氢酶和NAD用于甲酸的形成。

Methyl tert-butyl ether (MTBE) is ... metabolized to tert-butanol in rats. The metabolism of (14)C-MTBE has been studied in Fischer 344 rats exposed by the inhalation, oral, dermal, and intravenous routes. Respiratory and urinary metabolites were generally similar following exposure of Fischer 344 rats by all routes, indicating pathways are not route-dependent. After exposure by all routes, most of the exhaled radioactivity was due to unchanged MTBE and tert-butanol, with MTBE predominating. Only a small amount of (14)C-carbon dioxide was detected. MTBE and tert-butanol were generally not found in the urine, but four urinary metabolites were isolated, with two identified as alpha-hydroxyisobutyric acid and 2-methyl-1,2-propanediol. The two other metabolites remained unidentified. After inhalation and oral exposure, there was a larger fraction of exhaled tert-butanol in low dose rats than in high dose rats. In inhalation experiments, rats were exposed to (14)C-MTBE at 400 or 8000 ppm for 6 hr or to 400 ppm unlabeled MTBE for 6 hr per day for 14 days, then to 400 ppm (14)C-MTBE on day 15. tert-Butanol accounted for 25 and 30% of the recovered radioactivity in expired air at 3 hr after the single and repeated low exposure concentration, respectively. Exposure to the higher concentration for 6 hr resulted in a lower fraction recovered (7-10%) as a result of to tert-butanol. At 3-6 hr after exposure, tert-butanol represented 72-80% of the radioactivity at the low dose in the single and repeated exposure experiments and 43-54% at the high dose. Results of dosing Fischer 344 rats with (14)C-MTBE intravenously were similar to those obtained by the inhalation, oral and dermal routes. In Charles River CD (Sprague-Dawley) rats injected with a single intraperitoneal dose of 232 mg/kg (14)C-MTBE, blood, tissue, expired air, urine, and feces were sampled at various times up to 48 hr. At 6 hr about 92% of the radioactive dose was eliminated in expired air, 99.1% of which was unchanged MTBE. An average of 7.38% of the administered dose was expired as radiolabeled carbon dioxide. Analysis of the urine revealed that radiolabeled formic acid accounted for 96.6% of the urinary radioactivity. The remaining radioactivity in the urine was assumed to be radiolabeled methanol and formaldehyde. Methanol and formic acid were also detected in plasma, kidney, and liver. No tert-butanol was found in the urine. The metabolism of MTBE to formaldehyde was studied using liver microsomes from control and phenobarbital-pretreated rats (strain not specified). Phenobarbital pretreatment approximately doubled the formation of formaldehyde from MTBE. Further metabolism of formaldehyde yields methanol and/or formic acid; the probable enzymes and cofactors are alcohol dehydrogenase and NADH for the formation of methanol and aldehyde dehydrogenase and NAD for the formation of formic acid.

来源:Hazardous Substances Data Bank (HSDB)

代谢

之前已经表明，接触甲基叔丁基醚（MTBE）会改变各种肌肉、肾脏和肝脏的代谢活动。在当前研究中，研究了Sprague-Dawley大鼠经丙酮或苯巴比妥处理后肝脏微粒体对MTBE的代谢，MTBE浓度高达5 mM。通过顶空气相色谱测量，形成了等摩尔量的叔丁醇和甲醛。经丙酮和苯巴比妥处理后，去甲基化的Vmax分别增加了4倍和5.5倍。使用对照微粒体时的表观Km值为0.70 mM，在丙酮处理后略有下降，但在苯巴比妥处理后增加了2倍。单克隆抗体对p450IIE1的抑制了35%，这是对乙酮/乙醇诱导的细胞色素p450的可诱导形式，表明这种同种酶有部分贡献。大鼠单次预处理18小时，给予1或5 mL/kg MTBE（ip），导致肝脏微粒体对戊氧基香豆素去烷基酶活性增加了50倍，但对N-亚硝基二甲基胺去甲基酶活性没有变化。这些活性的趋势与免疫印迹分析一致，后者显示p450IIB1水平升高，而p450IIE1水平没有变化。

Exposure to methyl tertiary-butyl ether (MTBE) previously /has/ been shown to alter various muscle, kidney, and liver metabolic activities. In the present study, the metabolism of MTBE by liver microsomes from acetone- or phenobarbital-treated Sprague-Dawley rats was studied at concn of up to 5 mM MTBE. Equimolar amounts of tertiary- butanol, as measured by head-space gas chromatography, and formaldehyde were formed. The Vmax for the demethylation increased by 4 fold and 5.5 fold after acetone and phenobarbital treatments, respectively. The apparent Km value of 0.70 mM using control microsomes was decreased slightly after acetone treatment, but was increased by 2 fold after phenobarbital treatment. The metabolism of MTBE (1 mM) was inhibited by 35% by monoclonal antibodies against p450IIE1, the acetone/ethanol inducible form of cytochrome p450, suggesting a partial contribution by this isozyme. A single 18 hr pretreatment of rats with 1 or 5 mL/kg MTBE (ip) resulted in a 50 fold induction of liver microsomal pentoxyresorufin dealkylase activity but no change in N-nitrosodimethylamine demethylase activity. These trends in activity agreed with immunoblot analysis which showed an elevation in p450IIB1 but no change in p450IIE1 level.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类肝脏在ETBE（乙基叔丁基醚）和TAME（叔戊基甲醚）的氧化代谢中非常活跃。在15个人类肝脏微粒体样本中观察到了代谢这些汽油醚的个体间巨大差异。微粒体在代谢甲基叔丁基醚（MTBE）、乙基叔丁基醚（ETBE）和叔戊基甲醚（TAME）的活动之间高度相关（相关系数r，0.91-0.96），这表明这些醚类是通过相同的酶（s）进行代谢的。将醚代谢活性与肝脏微粒体中个体CYP酶活性进行相关性分析，结果显示与人类CYP2A6的相关性最高（相关系数r，0.90-0.95）... CYP2A6在表达于人类B淋巴母细胞的人类CYP酶中，对汽油醚的代谢显示出最高的转化数。对三种人类肝脏微粒体进行MTBE代谢的动力学研究表明，表观Km值范围为28至89微摩尔，V(max)值为215至783皮摩尔/分钟/毫克，具有相似的催化效率值（7.7至8.8微升/分钟/毫克蛋白质）。人类肝脏微粒体对MTBE、ETBE和TAME的代谢被香豆素抑制，香豆素是人类CYP2A6的已知底物，并且这种抑制是浓度依赖性的。针对人类CYP2A6的单克隆抗体显著地抑制了人类肝脏微粒体中MTBE、ETBE和TAME的代谢（抑制率为75%至95%）。...

/The/ human liver is active in the oxidative metabolism of ETBE and TAME. A large interindividual variation in metabolizing these gasoline ethers was observed in 15 human liver microsomal samples. The microsomal activities in metabolizing methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) were highly correlated among each other (r, 0.91-0.96), suggesting that these ethers are metabolized by the same enzyme(s). Correlation analysis of the ether-metabolizing activities with individual CYP enzyme activities in the liver microsomes showed that the highest degree of correlation was with human CYP2A6 (r, 0.90-0.95) ... CYP2A6 displayed the highest turnover number in metabolizing gasoline ethers among a battery of human CYP enzymes expressed in human B-lymphoblastoid cells. Kinetic studies on MTBE metabolism with three human liver microsomes exhibited apparent Km values that ranged from 28 to 89 uM and the V(max) values from 215 to 783 pmol/min/mg, with similar catalytic efficiency values (7.7 to 8.8 uL/min/mg protein). Metabolism of MTBE, ETBE, and TAME by human liver microsomes was inhibited by coumarin, a known substrate of human CYP2A6, in a concentration-dependent manner. Monoclonal antibody against human CYP2A6 caused a significant inhibition (75% to 95%) of the metabolism of MTBE, ETBE, and TAME in human liver microsomes. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

叔丁基甲醚的人类已知代谢物包括叔丁醇。

Tert-butyl methyl ether has known human metabolites that include tert-butanol.

来源:NORMAN Suspect List Exchange

毒理性

• 毒性总结

识别与用途：甲基叔丁基醚（MTBE）是一种无色液体。它被用作无铅汽油的辛烷值提升剂（体积含量最高可达7%）。人类研究：接触含有MTBE的摩托车燃料的人类出现了呼吸系统、过敏反应和神经系统反应频率增加的症状。人类的症状还包括头痛；恶心；呕吐；鼻子、口腔或喉咙的灼热感；咳嗽；眩晕；鼻出血；眼睛刺激；空间感和定向障碍；呼吸问题；疲劳；无法集中注意力；气短；焦虑；抑郁；胃痛；记忆力减退；失眠；以及食欲不振。吸入肺部可能会导致化学性肺炎。MTBE在200微摩尔浓度下可导致人淋巴细胞DNA双链断裂。动物研究：在动物研究中，MTBE具有中等急性毒性，会引起轻微的皮肤和眼睛刺激，但不会引起过敏。啮齿类动物重复接触主要影响肾脏和肝脏。接触MTBE会导致可逆的中枢神经系统（CNS）效应，包括镇静、活动减少、共济失调和较高浓度下的麻醉，以及较低浓度下对运动活动的双向效应。吸入MTBE的雄性大鼠肾脏和睾丸肿瘤的发生率增加，小鼠肝脏肿瘤的发生率增加。口服MTBE的雌性大鼠白血病和淋巴瘤（合并）的发生率增加，雄性大鼠睾丸肿瘤的发生率增加（见表格）。在低于对亲本有毒的浓度下，MTBE并未在啮齿类动物中引起不良的生殖或发育效应。在斑马鱼胚胎中，MTBE破坏了血管生成。在沙门氏菌试验和小鼠骨髓微核试验中，MTBE没有显示出遗传毒性。然而，雌性大鼠接触MTBE后，姐妹染色单体交换的统计学显著增加。生态毒性研究：连续三周暴露于低至0.11毫克/升的有效MTBE浓度下，显著增加了雄性斑马鱼（Danio rerio）的卵黄蛋白原浓度。在非洲鲶鱼（Clarias gariepinus）发育期接触MTBE，导致眼睛、口器和脊髓畸形以及幼虫死亡率增加。MTBE对各种水生生物的毒性浓度为57至1000毫克/升（无脊椎动物）和388-2600毫克/升（脊椎动物）。MTBE对蚯蚓种类有毒。生菜对MTBE最为敏感，其次是野燕麦、小麦和甜玉米（按敏感性递减顺序排列）。

IDENTIFICATION AND USE: Methyl tertiary-Butyl Ether (MTBE) is a colorless liquid. It is used as octane booster for unleaded gasoline (up to 7% by volume). HUMAN STUDIES: Humans exposed to motor fuel containing MTBE have experienced increase frequency of respiratory, allergic, and neurologic reactions. Symptoms in humans also include headaches; nausea; vomiting; burning sensation in the nose, mouth, or throat; cough; dizziness; nosebleeds; eye irritation; spaciness and disorientation; breathing problems; fatigue; inability to concentrate; shortness of breath; anxiety; depression; stomach cramps; poor memory; insomnia; and loss of appetite. Aspiration into the lungs may result in chemical pneumonitis. MTBE induced DNA double-strand breaks at 200 uM in human lymphocytes. ANIMAL STUDIES: In studies on animals, MTBE is moderately acutely toxic and induces mild skin and eye irritation but not sensitization. Repeated exposure in rodents affects primarily the kidney and the liver. Exposure to MTBE results in reversible central nervous system (CNS) effects including sedation, hypoactivity, ataxia and anesthesia at higher concentrations and biphasic effects on motor activity at lower concentrations. Inhalation exposure to MTBE produced increased incidences of kidney and testicular tumors in male rats and liver tumors in mice. Oral administration of MTBE produced increased incidences of leukemias and lymphomas (combined) in female rats and testicular tumors in male rats (see the table). MTBE has not induced adverse reproductive or developmental effects in rodents at concentrations less than those that were toxic to the parent. In zebrafish embryos MTBE disrupted angiogenesis. MTBE was not genotoxic in Salmonella assay and the mouse bone marrow micronucleus test. However, statistically significant increases in sister chromatid exchange were observed in female rats given MTBE. ECOTOXICITY STUDIES: Chronic exposure over three weeks to effective MTBE concentrations as low as 0.11 mg/L induced a significant increase in the vitellogenin concentration of male zebrafish (Danio rerio). In African catfish Clarias gariepinus developmental exposure to MTBE resulted in deformed eyes, mouthparts, and spinal cord and in increased larval mortality. MTBE is toxic to various aquatic organisms at concentrations of 57 to 1000 mg/L (invertebrates), and 388-2600 mg/L (vertebrates). MTBE was toxic to earthworm species. Lettuce was most sensitive to MTBE, followed (in order of decreasing sensitivity) by wild oats, wheat, and sweet corn.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

CASRN 1634-04-4 状态：已审查，但未列入致癌物报告（RoC）

CASRN 1634-04-4 Status: Reviewed but not listed in the Report on Carcinogens (RoC)

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3；已确认对动物有致癌性，但对人类的相关性未知。

A3; Confirmed animal carcinogen with unknown relevance to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于甲基叔丁基醚对人类致癌性的证据有限。对于甲基叔丁基醚对实验动物致癌性的证据有限。总体评估：甲基叔丁基醚的致癌性无法分类到对人类（第3组）。

Evaluation: There is limited evidence in humans for the carcinogenicity of methyl tert-butyl ether. There is limited evidence in experimental animals for the carcinogenicity of methyl tert-butyl ether. Overall evaluation: Methyl tert-butyl ether is not classifiable as to it carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：甲基叔丁基醚

IARC Carcinogenic Agent:Methyl tert-butyl ether

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

10名健康的男性志愿者在轻度体育锻炼期间，分别暴露于5、25和50 ppm的甲基叔丁基醚（MTBE）蒸汽中2小时。通过测量吸入和呼出的空气、血液和尿液中的MTBE和叔丁醇（TBA）来研究其吸收和分布。低吸收、高暴露后呼出和低血液清除率表明MTBE的代谢速度相对于许多其他溶剂较慢。尿液中TBA的回收率低（低于吸收量的1%）表明TBA进一步代谢。血液中MTBE和TBA的浓度与暴露水平成比例，提示在50 ppm以内呈线性动力学。血液和尿液中7-10小时的半衰期表明，TBA作为MTBE暴露的生物标志物比原化合物更为合适。主观评分（不适、刺激症状、中枢神经系统效应）以及眼部（红眼、泪膜破裂时间、结膜损伤、眨眼频率）和鼻子（最大呼气流量、声学鼻测量、鼻灌洗中的炎症标志物）的测量结果表明MTBE没有或仅有最小的影响。

... 10 healthy male volunteers /were exposed/ to methyl tert-butyl ether (MTBE) vapor at 5, 25 and 50 ppm for 2 hr during light physical exercise. Uptake and disposition were studied by measuring MTBE and tert-butyl alcohol (TBA) in inhaled and exhaled air, blood and urine. Low uptake, high post-exposure exhalation, and low blood clearance indicate slow metabolism of MTBE relative to many other solvents. A low recovery of TBA in urine (below 1% of uptake) indicates further metabolism of TBA. The concentration of MTBE and TBA in blood was proportional to exposure level suggesting linear kinetics up to 50 ppm. The half life of 7-10 hr in blood and urine indicates that TBA would be more suitable than the parent compound as a biomarker for MTBE exposure. Subjective ratings (discomfort, irritative symptoms, CNS effects) and eye (redness, tear film break-up time, conjunctival damage, blinking frequency) and nose (peak expiratory flow, acoustic rhinometry, inflammatory markers in nasal lavage) measurements indicated no or minimal effects of MTBE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吸入甲基叔丁基醚（MTBE）、乙基叔丁基醚（ETBE）和叔戊基甲基醚（TAME）后，它们能迅速被大鼠和人类吸收；在停止暴露后，大鼠通过呼出和生物转化为尿液代谢物的清除速度很快。与之相比，人类的呼出清除速度较慢。在相同条件下经呼吸道暴露后，MTBE和ETBE在人类和大鼠体内的生物转化在质和量上都是相似的。TAME的生物转化程度在大鼠和人类中也是相似的；然而，代谢途径是不同的。...

After inhalation exposure methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are rapidly taken up by both rats and humans; after termination of exposure, clearance by exhalation and biotransformation to urinary metabolites is rapid in rats. In humans, clearance by exhalation is slower in comparison to rats. Biotransformation of MTBE and ETBE is both qualitatively and quantitatively similar in humans and rats after inhalation exposure under identical conditions. The extent of biotransformation of TAME is also quantitatively similar in rats and humans; the metabolic pathways, however, are different. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

未指明品种的雌雄大鼠分组后，在鼻式吸入室中对甲基叔丁基醚（MTBE）蒸汽进行了一次6小时的暴露，目标MTBE浓度为400和8000 ppm，并连续15天每天重复6小时的400 ppm MTBE暴露。每组每性别四只大鼠随后被安乐死并接受检查。MTBE在大约4到6小时达到稳态血浆浓度，其主要代谢物叔丁醇（TBA）在大约6.5小时达到。在高浓度暴露期间，MTBE代谢酶饱和。MTBE的消除半衰期（t1/2）在单次低浓度和高浓度暴露后大致相同（分别为0.52和0.63小时）。在重复暴露后，MTBE的t1/2略短（分别为0.48和0.51小时）。TBA的t1/2在单次低浓度和高浓度暴露后范围为2.8到3.4小时。在重复暴露方案后，TBA的t1/2显著降低（雄性和雌性大鼠分别为1.8和1.5小时）。MTBE的药代动力学存在轻微但具有统计学意义的性别差异（例如，女性的血浆清除速度更快），但TBA的消除动力学没有观察到性别差异。

Groups of male and female rats /strain not specified/ received a single 6 hr exposure to methyl tert-butyl ether (MTBE) vapor in nose-only inhalation chambers at targeted MTBE concentrations of 400 and 8000 ppm and daily repeat 6 hr exposures for 15 days at a targeted MTBE concentration of 400 ppm. Four rats/sex/group were then euthanized and examined. Steady-state plasma concentrations were reached at approximately 4 to 6 hr for MTBE and roughly 6.5 hr for TBA /tert-butyl alcohol/, the principal metabolite of MTBE. MTBE-metabolizing enzymes were saturated during high-concentration exposure. The elimination half-life (t1/2) of MTBE was approximately the same after single low- and high-concentration exposures (0.52 and 0.63 hr, respectively). After the repeat exposures, the MTBE t1/2 was slightly shorter (0.48 and 0.51, respectively). The TBA t1/2 ranged from 2.8 to 3.4 hr after the low- and high-concentration single exposures. After the repeat exposure regimen, the TBA t1/2 was significantly lower (1.8 and 1.5 hr in the male and female rats, respectively). There was a slight, but statistically significant, sex difference in the pharmacokinetics of MTBE (e.g., plasma clearance was faster in females), but no sex differences in the elimination kinetics of TBA were observed.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在2名健康男性和2名健康女性暴露于1.7 ppm甲基叔丁基醚(MTBE) 1小时的研究中，平均血液中MTBE水平从接触前的0.83微克/升急剧上升到1小时接触结束时的17.14微克/升，随后在接触后40分钟下降到平均9.74微克/升，在接触后60分钟下降到6.32微克/升。

In a group of 2 healthy men and 2 healthy women experimentally exposed to 1.7 ppm methyl tert-butyl ether (MTBE) for 1 hr, mean blood levels of MTBE rose steeply from a level of 0.83 ug/L preexposure to 17.14 ug/L at the end of the 1-hr exposure, followed by a decline to an average level of 9.74 ug/L at 40 minutes postexposure and 6.32 ug/L at 60 minutes postexposure.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  3
• 危险品标志：
  F
• 安全说明：
  S16,S24,S36/37,S45,S9
• 危险类别码：
  R11,R38
• WGK Germany：
  3
• 海关编码：
  2909199090
• 危险品运输编号：
  UN 2398 3/PG 2
• 危险类别：
  3
• RTECS号：
  KN5250000
• 包装等级：
  II
• 危险标志：
  GHS02,GHS07
• 危险性描述：
  H225,H315
• 危险性防范说明：
  P210,P370 + P378,P403 + P235
• 储存条件：
  储存注意事项： - 储存于阴凉、通风的库房。 - 远离火种、热源，库温不宜超过37℃。 - 保持容器密封，并与氧化剂分开存放，切忌混储。 - 使用防爆型照明和通风设施。 - 禁止使用易产生火花的机械设备和工具。 - 储区应备有泄漏应急处理设备和合适的收容材料。

SDS

第一部分：化学品名称

制备方法与用途

甲基叔丁基醚（MTBE）简介

甲基叔丁基醚（MTBE），熔点-109℃，沸点55.2℃，是一种无色、透明的高辛烷值液体。它曾被认为在80年代是理想的第三代石油化学品，能够提高无铅汽油的氧含量，使汽油燃烧更充分，减少一氧化碳和苯等有害物质的排放，并可替代四乙基铅作抗暴剂。由于这些特性，MTBE需求量迅速增长，成为生产高辛烷值无铅汽油的理想添加剂。

理化性质

甲基叔丁基醚（MTBE）是生产无铅、高辛烷值含氧汽油的优良调合组分。它不仅有效提高汽油辛烷值，还能改善汽车性能，降低排气中CO含量，并且降低了汽油生产成本。此外，MTBE还是一种重要的化工原料，可以通过裂解制备异丁烯，作为橡胶及其他化工产品的原料。

然而，当前去产能化趋势明显，使用量有所下降。

应用

目前甲基叔丁基醚主要应用于以下几个方面：

1. 作为汽油添加剂：超过90%的MTBE用于此目的。
2. 裂解为高纯度异丁烯：用于生产MMA（甲基丙烯酸甲酯）和异戊二烯等。
3. 有机合成原料：如2-甲基丙烯醛、甲基丙烯酸。

化学性质

甲基叔丁基醚是一种无色、低粘度液体，具有类似萜烯的气味。微溶于水，并与许多有机溶剂和汽油互溶。它可以与一些极性溶剂形成共沸物，并且有轻度麻醉作用。

用途

1. 作为汽油添加剂：替代四乙基铅，提高辛烷值。
2. 色谱中用作脱剂，尤其是高压液相色谱。
3. 有机合成原料，用于制备异丁烯、甲基丙烯醛及甲基丙烯酸等。

生产方法

以混合丁烯和甲醇为原料，在酸性催化剂存在下进行放热反应而获得。具有代表性的工艺包括德国赫斯公司和意大利SNAM Progetti公司的技术，美国化学研究许可证公司（ACRL）和新化学公司开发的催化精馏新技术也已投入使用。

物理性质

• 类别：易燃液体
• 毒性分级：中毒
• 急性毒性：
  • 口服：大鼠 LD50 >4000 毫克/公斤
  • 吸入：小鼠 LC50 <141 克/立方米（15分钟）
• 刺激数据：
  • 皮肤接触：兔子，10毫克/24小时，轻度刺激
  • 眼睛接触：兔子，50微克，重度刺激

安全信息

• 爆炸物危险特性：与空气混合形成爆炸性混合物。
• 可燃性危险特性：易燃，在火场会产生辛辣刺激烟雾。
• 储运特性：
  • 库房应通风、低温干燥
  • 避免与氧化剂分开储存

灭火方法

干粉、二氧化碳、1211灭火器及泡沫均可用于扑灭火灾。

• 职业标准
  • 时间加权平均容许浓度（TWA）：100 毫克/立方米
  • 短时间接触容许浓度（STEL）：200 毫克/立方米

反应信息

• 作为反应物：
  描述：

  甲基叔丁基醚 在 salhen(^tBu)[BBr₂]2 作用下， 以 chloroform-d1 为溶剂， 反应 24.0h， 生成 溴甲烷
  参考文献：
  名称：

  Catalytic cleavage of phosphate ester bonds by boron chelates

  摘要：

  揭示了具有一般公式L{YXm}n的新化合物，其中X选自第13族元素，Y是卤素，L是含有至少一个与第13族元素接触的结合原子的螯合配体，所述原子选自C、N、O和S组成的组，m和n是至少为1的整数。 L可以是席夫碱型配体，如salen配体。本发明的组合物可以是双齿、四齿或更多齿的。这些组合物可以用于磷酸酯或醚的去烷基化。优点是，本发明的方法可以具有催化性。

  公开号：

  US07166591B1
• 作为产物：
  描述：

  甲丁醚 在 氯 作用下， 生成 甲基叔丁基醚
  参考文献：
  名称：

  Process for the preparation of

  摘要：

  4-羟基-2,4,6-三甲基-2,5-环己二烯酮是通过在有机溶剂中在无碱存在的情况下使用氯气氯化2,4,6-三甲基苯酚制备的，同时生成的氢氯酸气体通过物理手段去除，并可选择性地在水中与反应混合物水解，也可以在无机碱的存在下进行。

  公开号：

  US04612401A1
• 作为试剂：
  描述：

  十二醛 在 S-α,α-双(3,5-二三氟甲基苯基)脯氨醇三甲基硅醚 、 锂硼氢 、 甲基叔丁基醚 、 戴斯-马丁氧化剂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N-氟代双苯磺酰胺 、 D-脯氨酸 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 14.67h， 生成 dibenzyl 1-((2S,4S)-4-fluoro-1-hydroxytetradecan-2-yl)hydrazine-1,2-dicarboxylate
  参考文献：
  名称：

  顺式/反式-α-肼基-γ-氟醇对映选择性合成的有机催化路线

  摘要：

  开发了一种通用的有机催化方法用于不对称合成α-肼基-γ-氟醇，顺式/反式1,3-氟胺的前体。该策略采用脯氨酸衍生催化剂、(S)-α,α-双[3,5-()]-2-吡咯烷甲醇三甲基硅醚催化的α-氟化，然后进行醛的霍纳-沃兹沃斯-埃蒙斯(HWE)烯化，脯氨酸催化的α-氨基化为关键步骤。标题化合物表现出优异的非对映选择性（高达 99:1）和对映选择性（高达 99%）。

  DOI：

  10.1016/j.tetlet.2024.155179

文献信息

• Reactions in Slightly Hydrated Solid/Liquid Heterogeneous Media: The Methylation Reaction with Dimethyl Sulfoxide
  作者：D. Achet、D. Rocrelle、I. Murengezi、M. Delmas、A. Gaset

  DOI：10.1055/s-1986-31729

  日期：——

  The O-methylation of alcohols and phenols with stoichiometric amounts of dimethyl sulfate in 1,4-dioxan or triglyme in the presence of solid potassium hydroxide and small amounts of water represents a useful method for the synthesis of methylethers in high yields and with high selectivity. The complete consumption of dimethyl sulfate in this reaction avoids the problems connected with the work-up of reaction mixtures still containing excess amounts of this toxic reagent.

  在固体氢氧化钾和少量水的存在下，使用二甲基硫酸酯和1,4-二氧六环或三甘醇的定量摩尔量对醇和酚进行O-甲基化，是一种合成甲醚的高产率和高选择性的有用方法。该反应中二甲基硫酸酯的完全消耗避免了与含有过量这种有毒试剂的反应混合物后处理相关的问题。
• COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
  申请人：Van Goor Fredrick F.

  公开号：US20110098311A1

  公开（公告）日：2011-04-28

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及包含上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• Bis-(N,N'-bis-(2-haloethyl)amino)phosphoramidates as antitumor agents
  申请人：Telik, Inc.

  公开号：US06506739B1

  公开（公告）日：2003-01-14

  Bis-(N,N′-bis-(2-haloethyl)amino)phosphoramidates, pharmaceutical compositions containing them, methods of treatment using them, and processes for their preparation. The compounds possess anti-tumor activities or are capable of being modified to have anti-tumor activities; and this invention relates to the use of the compounds in methods for the treatment of tumors and, especially, for the treatment of cancer.

  双-(N,N′-双-(2-卤乙基)氨基)磷酰胺酯，含有它们的药物组合物，使用它们的治疗方法，以及它们的制备方法。这些化合物具有抗肿瘤活性或能够被改造为具有抗肿瘤活性；本发明涉及将这些化合物用于肿瘤治疗方法，特别是用于癌症治疗的方法。
• Pyrrolidine modulators of chemokine receptor activity
  申请人：Merck & Co., Inc.

  公开号：US06265434B1

  公开（公告）日：2001-07-24

  The present invention is directed to pyrrolidine compounds of the formula 1: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

  本发明涉及式1的吡咯烷化合物：（其中R1、R2、R3、R4、R5、R6和n在此处定义），这些化合物可用作趋化因子受体活性的调节剂。具体来说，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。
• Carboxamides useful as inhinitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
  申请人：——

  公开号：US20030109700A1

  公开（公告）日：2003-06-12

  1 Compounds of formula (1) wherein R 2 —C, R 3 —C, R 4 —C or R 5 —C may be replaced by N; and wherein n is 1, 2 or 3; R 1 is aryl, heteroaryl or (aryl or heteroaryl)-lower alkoxy; R 2 , R 3 , R 4 and R 5 are independently hydrogen, lower alkyl, lower alkoxy, halo, trifluoromethyl or cyano; R 6 is (i) or (ii) m is 1, 2 or 3; R 7 is hydrogen, lower alkyl (aryl or heteroaryl)-lower alkyl, lower alkoxy, (aryl or heteroaryl)-lower alkoxy, hydroxy, oxo, lower alkylenedioxy or lower alkanoyloxy; W is O, S or NR 8 ; R 8 is —COR a , (iii), —COOR d , —SO 2 R e , hydrogen, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R a , R d and R e , are independently optionally substituted lower alkyl, cycloalkyl, adamantyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R b and R c are independently hydrogen, cycloalkyl, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl) lower alkyl; or R b and R c together represent lower alkylene; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (apoB) secretion.

  式（1）的化合物中，其中R2—C，R3—C，R4—C或R5—C可以被N取代；其中n为1、2或3；R1为芳基，杂环芳基或（芳基或杂环芳基）-较低烷氧基；R2、R3、R4和R5独立地为氢、较低烷基、较低烷氧基、卤素、三氟甲基或氰基；R6为（i）或（ii）m为1、2或3；R7为氢、较低烷基（芳基或杂环芳基）-较低烷基、较低烷氧基、（芳基或杂环芳基）-较低烷氧基、羟基、氧代、较低烷二氧基或较低烷酰氧基；W为O、S或NR8；R8为—CORa、（iii）、—COORd、—SO2Re、氢、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Ra、Rd和Re独立地为可选择取代的较低烷基、环烷基、脱氢脂肪基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Rb和Rc独立地为氢、环烷基、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）较低烷基；或Rb和Rc一起代表较低烷基；以及其药学上可接受的盐；以及其对映体；它们可用作微粒体三酰甘油转移蛋白（MTP）和载脂蛋白B（apoB）分泌的抑制剂。

表征谱图