甲基丙烯酸甲酯 | 80-62-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甲基丙烯酸甲酯
• 中文别名: 异丁烯酸甲酯；甲基败脂酸甲酯,2-甲基-2-丙烯酸甲酯,异丁烯酸甲酯；2-甲基-2-丙烯酸甲酯；有机玻璃单体；MMA；甲甲酯
• 英文名称: methacrylic acid methyl ester
• 英文别名: 2-methyl-2-propenoic acid methyl ester；poly(methyl methacrylate)；methyl methacrylate；MMA；methyl 2-methylprop-2-enoate；methyl 2-methacrylate
• CAS: 80-62-6
• 化学式: C₅H₈O₂
• mdl: MFCD00008587
• 分子量: 100.117
• InChiKey: VVQNEPGJFQJSBK-UHFFFAOYSA-N

物化性质

• 熔点：
  -48 °C (lit.)
• 沸点：
  100 °C (lit.)
• 密度：
  0.936 g/mL at 25 °C (lit.)
• 蒸气密度：
  3.5 (vs air)
• 闪点：
  50 °F
• 溶解度：
  15g/l
• 介电常数：
  2.9（20℃）
• 暴露限值：
  NIOSH REL: TWA 100 ppm (410 mg/m3), IDLH 1,000 ppm; OSHA PEL: TWA 100 ppm; ACGIH TLV: TWA 100 ppm with intended TWA and STEL values of 50 and 100 ppm, respectively.
• LogP：
  1.38 at 20℃
• 物理描述：
  Methyl methacrylate monomer appears as a clear colorless liquid. Slightly soluble in water and floats on water. Vapors heavier than air. Vapors irritate the eyes and respiratory system. Containers must be heavily insulated or shipped under refrigeration. An inhibitor such as hydroquinone, hydroquinone methyl ester and dimethyl t-butylphenol is added to keep the chemical from initiating polymerization. The chemical may polymerize exothermically if heated or contaminated with strong acid or base. If the polymerization takes place inside a container, the container may rupture violently. Used to make plastics.
• 颜色/状态：
  Colorless volatile liquid
• 气味：
  Characteristic quality: sulfur-like, sweet, sharp; hedonic tone: unpleasant
• 蒸汽密度：
  3.45 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  38.5 mm Hg at 25 °C
• 大气OH速率常数：
  2.60e-11 cm3/molecule*sec
• 自燃温度：
  815 °F (435 °C)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 燃烧热：
  -11,400 BTU/lb = 6,310 cal/g = -264X10+5 J/kg (estimated)
• 汽化热：
  36.0 kJ/mol at 100.5 °C
• 表面张力：
  0.028 N/m at 20 °C.
• 电离电位：
  9.70 eV
• 聚合：
  The monomer tends to self-polymerize and this may become explosive ... Exposure of the purified (unstabilized) monomer to air at room temp for 2 months generated an ester-oxygen interpolymer, which exploded on evaporation of the surplus monomer at 60 °C (but not at 40 °C).
• 气味阈值：
  0.05 ppm
• 折光率：
  Index of refraction: 1.4142 at 20 °C
• 相对蒸发率：
  3.1 (Butyl acetate = 1)
• 保留指数：
  723;672;696;700;694;677;699;677;677;677;710;699;696;694.1;696.1;696;696;699;692.9;677;699
• 稳定性/保质期：
  1. 易挥发，易燃，能与空气形成爆炸性混合物。它溶于乙醇、乙醚、丙酮等多种有机溶剂，并微溶于乙二醇和水。受光、热及催化作用容易聚合，也可与其他单体共聚；由于含有双键和羧酸基团，还易进行加成、卤化、亲核取代以及酯交换反应。通常需要加入10-5%的氢醌单甲醚作为阻聚剂。 2. 本品毒性较小。大鼠经口LD₅₀为9400mg/kg，吸入致死浓度Lc₅₀为15.33g/m³，其作业最高容许浓度为410mg/m³。然而，其嗅阈值在130~250mg/m³之间，即使在还未达到毒性浓度之前，强烈的气味就已经让人难以忍受。人体皮肤接触甲基丙烯酸甲酯后，只有极少数人会出现红疹。 3. 由于生产甲基丙烯酸甲酯的原料氰化钠和中间体氰化氢均剧毒，因此必须严格确保生产设备密闭，并保持良好的通风条件。操作人员应配备必要的防护装备，并在发现中毒现象时立即移至空气新鲜处进行及时抢救。 4. 稳定性：稳定。 5. 禁配物：氧化剂、酸类、碱类、还原剂、过氧化物、胺类及卤素。 6. 应避免接触的条件：受热、光照、紫外线以及与空气接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

MMA的代谢在雄性Wistar大鼠中进行了研究，这些大鼠通过口服灌胃的方式摄入了C2位上放射性标记的MMA（5.7 mg/kg）或连接在C2上的甲基团（120 mg/kg）的MMA，载体为玉米油。单次剂量的甲基(1,3-(14)C)丙烯酸-2-甲酯或甲基(2-(14)C)丙烯酸-2-甲酯的65%在给药后2小时内以(14)CO2的形式呼出，10天内呼出的比例为76 - 88%。在甲基(1,3-(14)C)丙烯酸-2-甲酯（5.7 mg/kg）的情况下，未改变的MMA通过肺排泄的比例不到剂量的1%，而在120 mg/kg的甲基(2-(14)C)丙烯酸-2-甲酯后，这一比例为1.4%。大约50%的剩余剂量通过尿液排出，10天后剩余的部分保留在体内组织中。消除模式与剂量没有显著差异，但在较高剂量下MMA的代谢速度较慢。从用甲基(1,3-(14)C)丙烯酸-2-甲酯处理的鼠尿中，确定了以下含(14)C的代谢物：甲基丙烯酸（占剂量的0.8%）、甲基丙二酸（1.1%）、琥珀酸（0.2%）、2种与β-羟基异丁酸和甲酰-2-丙酸共洗脱的次要代谢物（甲基丙二酸半醛）。(14)C尿素（2%）和H14CO3-被认为是来自(14)CO2。作者得出结论，MMA通过生理途径代谢，并通过甲基丙二酸CoA和琥珀酰-CoA进入三羧酸循环，这是缬氨酸途径的一部分。

The metabolism of MMA was studied in male Wistar rats after oral gavage of MMA radiolabeled on the C2 position (5.7 mg/kg) or the methyl group attached to the C2 (120 mg/kg) in corn oil. A total of 65% of a single dose of methyl (1,3-(14)C)propylene-2-carboxylate or methyl (2-(14)C)-propylene-2-carboxylate was exhaled as (14)CO2 within 2 hr of administration, and 76 - 88% was exhaled with 10 days. Pulmonary excretion of unchanged MMA accounted for < 1% of the dose in the case of methyl (1,3-(14)C)propylene-2-carboxylate (5.7 mg/kg) and for 1.4% of the dose after 120 mg/kg of methyl (2-(14)C)propylene-2-carboxylate. Approximately 50% of the remaining dose was excreted in urine, the remainder being retained in body tissues after 10 days. The elimination pattern did not differ significantly with the dose, but MMA was metabolized more slowly at the higher dose. From the urine of rats treated with methyl (1,3-(14)C)propylene-2-carboxylate, the following (14)C-containing metabolites were identified: methacrylic acid (0.8% of the dose), methylmalonic acid (1.1%), succinic acid (0.2%), 2 minor metabolites co-eluting with beta-hydroxyisobutyric acid and formyl-2-propionic acid (methylmalonic semialdehyde). (14)C urea (2%) and H14CO3- were assumed to be derived from (14)CO2. The authors conclude that MMA is metabolized via physiological pathways and enters into the citric acid cycle via methyl-malonyl CoA and succinyl-CoA, which is a part of the valine pathway.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 甲硫氨酸的体外代谢是使用雄性Wistar大鼠的肝脏切片进行研究的。其中一些制剂先与柠檬酸循环中某些步骤的抑制剂预孵育，包括砒霜（1 mM）或丙二酸（10 mM）。甲硫氨酸的代谢与柠檬酸循环的自然中间产物琥珀酸进行了比较，发现它们非常相似。由于丙二酸并未发现能抑制甲硫氨酸的代谢，而砒霜却能非常有效地抑制，作者得出结论，甲硫氨酸是通过丙酮酸而非琥珀酰辅酶A进行代谢的。

... The in vitro metabolism of MMA /was studied/ using liver slices of male Wistar rats. Some of the preparations were preincubated with inhibitors of certain steps of the citric acid cycle, arsenite (1 mM) or malonate (10 mM). Metabolism of MMA was compared to that of the natural intermediate of the citric acid cycle, fumarate, and found to be very similar. As malonate was not found to inhibit MMA metabolism, but arsenite inhibited it very effectively, the authors concluded that MMA is metabolized via pyruvate rather than succinyl-CoA.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在向分离的大鼠肝细胞制剂中添加0、2、5和10 mM的MMA，并在37°C下孵化2小时后，观察到细胞内还原型谷胱甘肽（GSH）的浓度和时间依赖性耗竭。在孵化30分钟后，GSH含量达到最低。随后，GSH水平恢复正常，所需时间与MMA浓度有关。2小时后，与浓度相关的GSH耗竭仍然可以观察到。通过细胞质膜的完整性监测肝细胞的活性，并未受到MMA处理的损害。MMA对细胞内细胞色素P-450血红蛋白的含量没有影响。

Following the addition of 0, 2, 5 and 10 mM MMA to isolated rat hepatocyte preparations and incubation for 2 hr at 37 °C, a concentration and time dependent depletion of reduced glutathione (GSH) in the cells was observed. A minimum GSH content was reached after 30 min incubation. GSH levels then returned to normal, the time required being a function of the MMA concentration. After 2 hr the concentration-related GSH depletion was still observable. The viability of the hepatocytes, monitored by the integrity of the plasma membrane, was not impaired by MMA treatment. MMA had no effect on the content of cytochrome P-450 hemoprotein of the cells.

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲基丙烯酸甲酯（1 mM或5 mM）在与25%大鼠肝脏上清液孵育1小时或3小时时，在磷酸缓冲液（pH 6.5）中并未与谷胱甘肽（2 mM）发生反应。谷胱甘肽-S-环氧化物转移酶在MMA存在时无活性，这是通过谷胱甘肽的损失来确定的。尽管在大鼠肝脏上清液中可以识别出一种催化α,β-不饱和化合物与谷胱甘肽反应的单独酶，但这种酶并未催化MMA与谷胱甘肽的反应。

Methyl methacrylate (1 mM or 5 mM) did not react with GSH (2 mM) in phosphate buffer (pH 6.5) when incubated with 25% rat liver supernatant for 1 or 3 hr. The enzyme glutathione-S-epoxide transferase was not active in the presence of MMA as determined by GSH loss. Although a separate enzyme in rat liver supernatant, catalyzing the reaction of alpha, beta-unsaturated compounds with GSH could be identified, this enzyme did not catalyze the reaction of MMA with GSH.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别：甲基丙烯酸甲酯是一种挥发性合成化学品，主要用于生产铸模丙烯酸板材、丙烯酸乳液以及注塑和挤出树脂。人类暴露：关于经皮肤暴露吸收的数据有限。在人类中，甲基丙烯酸甲酯迅速代谢为甲基丙烯酸。这种化合物在人类中是轻微的皮肤刺激剂，并且有可能在易感个体中诱导皮肤致敏。尽管也有关于与甲基丙烯酸甲酯相关的职业性哮喘的报道，但没有确凿的证据表明这种化合物是呼吸道的致敏剂。流行病学研究没有提供甲基丙烯酸甲酯对人类任何靶器官具有致癌效应的强烈或一致证据，也无法确信地推断出增加风险的可能性已被否认。 动物/植物研究：甲基丙烯酸甲酯在实验动物经吸入或口服给药后迅速吸收和分布。关于经皮肤暴露吸收的数据有限。在实验动物中，甲基丙烯酸甲酯迅速代谢为甲基丙烯酸。在大鼠吸入后，约16-20%的化学物质沉积在上呼吸道，主要在局部组织酯酶的作用下代谢。该化合物的急性毒性较低。在暴露于相对高浓度甲基丙烯酸甲酯的啮齿动物和兔子上，观察到皮肤、眼睛和鼻腔的刺激。在动物中，该化合物是轻微的皮肤致敏剂。在重复吸入暴露于该化合物后，在最低浓度下最常观察到的影响是鼻腔刺激。在更高浓度下，对肾脏和肝脏的影响已有报道。据报道，大鼠接触该物质2年后，引起鼻腔上皮炎症性退化的最低影响水平为410 mg/立方米；在这项调查中，无观察到效应水平（NOEL）大约为100 mg/立方米。在一项大鼠研究中，尽管母体体重在吸入浓度高达8315 mg/立方米的条件下有所减轻，但没有观察到发育影响。在雄性小鼠接触该化合物浓度高达36900 mg/立方米的条件下，没有观察到生育力下降，并且在迄今为止进行的重复剂量研究中，对生殖器官没有不良影响。关于甲基丙烯酸甲酯的神经毒性数据有限；在口服暴露于500 mg/kg体重/天，持续21天的大鼠中，观察到运动活动受损和大脑的学习和行为影响。在为期2年的大鼠和小鼠吸入暴露的广泛且良好记录的生物鉴定中，甲基丙烯酸甲酯并未表现出致癌性，以及在额外的慢性大鼠和仓鼠吸入研究中也未表现出致癌性。在体外细菌系统中，这种物质不是致突变剂，但在哺乳动物细胞体外，这种化合物是致突变剂和致裂剂。在体内研究中（主要通过吸入途径），在靶组织中已有明确的毒性证据，但甲基丙烯酸甲酯的遗传毒性证据有限。 甲基丙烯酸甲酯对水生生物的毒性较低。没有识别出对水生生物的慢性研究。对鱼类、大型溞和藻类进行了急性测试。最敏感的影响是在8天暴露期后，绿藻四尾栅藻细胞增殖抑制的开始，浓度为37 mg/L。大型溞的最低EC50为720 mg/L。在流水条件下，幼年蓝鳃太阳鱼（Lepomis macrochirus）的96小时LC50为191 mg/L，而1-24小时的LC50值分别为420-356 mg/L。在流水条件下，虹鳟鱼（Oncorhynchus mykiss）的96小时LC50大于79 mg/L，这是测试的最高浓度。在40 mg/L的鱼类中观察到了亚致死/行为反应。

IDENTIFICATION: Methyl methacrylate is a volatile synthetic chemical that is used principally in the production of cast acrylic sheet, acrylic emulsions, and molding and extrusion resins. HUMAN EXPOSURE: Data on absorption following dermal exposure are limited. In humans, methyl methacrylate is rapidly metabolized to methacrylic acid. This compound is a mild skin irritant in humans and has the potential to induce skin sensitization in susceptible individuals. Although occupational asthma associated with methyl methacrylate has also been reported, there is no conclusive evidence that this compound is a respiratory sensitizer. Epidemiological studies do not provide strong or consistent evidence of a carcinogenic effect of methyl methacrylate on any target organ in humans, nor can it be inferred with any degree of confidence that the possibility of an increased risk has been disapproved. ANIMAL/PLANT STUDIES: Methyl methacrylate is rapidly absorbed and distributed following inhalation or oral administration to experimental animals. Data on absorption following dermal exposure are limited. In experimental animals, methyl methacrylate is rapidly metabolized to methacrylic acid. Following inhalation, 16-20% of the chemical is deposited in the upper respiratory tract of rats, where it is primarily metabolized by local tissue esterases. The acute toxicity of this compound is low. Irritation of the skin, eye and nasal cavity has been observed in rodents and rabbits exposed to relatively high concentrations of methyl methacrylate. The chemical is a mild skin sensitizer in animals. The effect observed most frequently at the lowest concentration after repeated inhalation exposure to this compound is irritation of the nasal cavity. Effects on the kidney and liver at higher concentrations have been reported. The lowest reported effect level for irritation was 410 mg/cu m in rats exposed to this material for 2 yr (based upon inflammatory degeneration of the nasal epithelium); the no observed effect level (NOEL) in this investigation was approximately 100 mg/cu m. In a study in rats, there were no developmental effects, although there were decreases in maternal body weight following inhalation of concentrations up to 8,315 mg/cu m. There was no reduction in fertility in a dominant lethal assay in mice exposed to this compound at concentrations up to 36,900 mg/cu m and no adverse effects on reproductive organs in repeated dose studies conducted to date. Available data on the neurotoxicity of methyl methacrylate are limited; impairment of locomotor activity and learning and behavioral effects on the brain were observed in rats exposed orally to 500 mg/kg bw/day for 21 days. Methyl methacrylate was not carcinogenic in an extensive well documented 2 yr bioassay in rats and mice exposed by inhalation and in additional chronic inhalation studies in rats and hamsters. This substance is not mutagenic in in vitro bacterial systems, this compound is mutagenic and clastogenic in mammalian cells in vitro. In in vivo studies (primarily by the inhalation route) in which there has been clear evidence of toxicity within the target tissue, there has been limited evidence of the genotoxicity of methyl methacrylate. The toxicity of methyl methacrylate to aquatic organisms is low. No chronic studies on aquatic organisms were identified. Acute tests have been conducted on fish, Daphnia magna and algae. The most sensitive effect was the onset of inhibition of cell multiplication by the green alga Scenedesmus quadricauda at 37 mg/l following an 8 day exposure period. The lowest EC50 for immobilization in Daphnia was 720 mg/L. The 96 hr LC50 for juvenile bluegill sunfish (Lepomis macrochirus) under flow through conditions was 191 mg/L, whereas LC50 values for durations 1-24 hr ranged from 420-356 mg/L, respectively. The 96 hr LC50 for rainbow trout (Oncorhynchus mykiss) under flow through conditions was > 79 mg/L, the highest concentration tested. Sublethal/behavioral responses were noted among the fish at 40 mg/L.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于甲基丙烯酸甲酯在人类中的致癌性，现有证据不足。有证据表明，在实验动物中甲基丙烯酸甲酯不具有致癌性。总体评估：甲基丙烯酸甲酯的致癌性对人类而言无法分类（第3组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of methyl methacrylate. There is evidence suggesting lack of carcinogenicity of methyl methacrylate in experimental animals. Overall evaluation: Methyl methacrylate is not classifiable as to its carcinogenicity to humans (Group3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

证据权重特征：根据美国环保局1986年的致癌风险评估指南，甲基丙烯酸甲酯（MMA）将被归类为对人类非致癌性证据或E组化学品。在拟议的致癌风险评估指南下，由于在三种适当的动物物种进行的四项良好进行的慢性吸入研究中没有显示出致癌效果，因此认为MMA不太可能通过任何暴露途径对人类致癌。依据 - 为NTP进行的两年吸入研究的结果显示，在500或1000 ppm暴露的雄性F344/N大鼠、在250或500 ppm暴露的雌性F344/N大鼠、以及在500或1000 ppm暴露的雌性B6C3F1小鼠中，都没有显示出MMA的致癌性。此外，从Hazelton实验室在1979年进行的慢性吸入研究中，大鼠和仓鼠的肿瘤数量或类型也没有增加。在慢性口服研究中没有报告致癌活性。这项口服研究的实验方案和结果没有像吸入研究那样记录得很好，使用的动物数量也较少。然而，急性口服暴露研究和对其他丙烯酸酯的结构-活性关系比较表明，向丙烯酸部分引入甲基团（例如，EC到MMA）会消除致癌活性。流行病学研究没有显示癌症有明显的增加。尽管有报告建议在暴露于乙基丙烯酸酯/MMA的工人中结肠癌增加，但已经记录了该研究地点和时间的高背景效应，其他类似且更新的研究没有复制这些效果，没有明确显示暴露与效应之间的关系，并且无法确定乙基丙烯酸酯同时暴露对结果的影响程度。鉴于这些结构-活性关系考虑，遗传毒性、实验室动物和流行病学研究显示的MMA暴露的低癌症潜力表明，MMA对人类不具有致癌风险。人类致癌性数据：不充分。动物致癌性数据：无证据。

WEIGHT OF EVIDENCE CHARACTERIZATION: Under EPA's 1986 Guidelines for Carcinogen Risk Assessment, MMA would be classified as evidence of non-carcinogenicity for humans or a Group E chemical. Under the Proposed Guidelines for Carcinogenic Risk Assessment, MMA is considered not likely to be carcinogenic to humans by any route of exposure because it has been evaluated in four well-conducted chronic inhalation studies in three appropriate animal species without demonstrating carcinogenic effects. Basis - The results of the 2-year inhalation studies conducted for NTP showed no evidence of carcinogenicity of MMA for male F344/N rats exposed at 500 or 1,000 ppm, for female F344/N rats exposed at 250 or 500 ppm, or for female B6C3F1 mice exposed at 500 or 1,000 ppm. In addition, no increase was seen in the number or type of tumors in either rats or hamsters from the chronic inhalation study performed by Hazelton Laboratories /in 1979/. No carcinogenic activity was reported in a chronic oral study. Fewer animals were used and the experimental protocol and results of this oral study were not as well documented as for the inhalation study. However, acute oral exposure studies and structure-activity relationship comparisons with other acrylates suggest that the introduction of a methyl group to the acrylate moiety (e.g., EC to MMA) negates carcinogenic activity. Epidemiology studies show no clear excess of cancer. Though a report suggesting increased colon cancer among ethyl acrylate/MMA-exposed workers exists, a high background for this effect has been documented for the location and time of this study, the effects were not reproduced in other similar and more recent studies, a clear relationship between exposure and effect was not demonstrated, and the extent that ethyl acrylate concurrent exposure confounded results could not be determined. Given these structure-activity relationship considerations, the low potential for cancer from MMA exposure indicated in genotoxicity, laboratory animal and epidemiology studies suggests that MMA does not represent a carcinogenic hazard to humans. HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: No evidence.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A4；不可分类为人类致癌物。

A4; Not classifiable as a human carcinogen.

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：甲基丙烯酸甲酯

IARC Carcinogenic Agent:Methyl methacrylate

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

在给予三只Alderley Park雄性大鼠静脉注射1,3-(14)C-甲基丙烯酸甲酯（10 mg/kg，50 uCi/kg，溶于聚乙二醇2000/乙醇1:1）后，通过全身放射自显影研究了给药后2、5和15分钟时放射活性的组织分布。无论处死时间如何，血液、心脏、肺、肝脏、肾脏和唾液腺中放射活性的浓度最高。其他含有较少放射活性的组织包括睾丸，其中一部分放射活性位于精囊中。在这项研究中，无法确定任何组织中的放射活性是由于MMA或其代谢物的存在。

The tissue distribution of radioactivity after iv administration of 1,3-(14)C-methyl methacrylate (10 mg/kg, 50 uCi/kg in polyethyleneglycol 2000/ethanol 1:1) to three male Alderley Park rats was studied by whole body autoradiography. The rats were killed at 2, 5, and 15 min after dosing. Irrespective of the time of sacrifice, the greatest concentrations of radioactivity were determined in blood, heart, lungs, liver, kidneys, and salivary glands. Other tissues containing smaller amounts of radioactivity included the testes, where some of the radioactivity was located in the seminal vesicles. In this study it was not possible to determine whether the radioactivity in any of the tissues was due to the presence of MMA or its metabolites.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在11名牙科技术员接触MMA（甲基丙烯酸甲酯）30至240分钟后（未报告剂量水平），在接触后24小时内，尿液中排泄了19至200纳摩尔甲基丙烯酸。由于本研究未测量暴露浓度，因此无法建立暴露与尿液中水平的相关性。排泄的甲基丙烯酸浓度显示出个体间差异较大，并不一致与暴露时间相关。作者指出，由于牙科实验室通常工作场所浓度较低，吸入暴露不会导致观察到的甲基丙烯酸尿液水平。然而，研究中并未确定空气中的水平。

After dermal exposure of 11 dental technicians to MMA for 30 - 240 min (dose levels not reported), 19 - 200 nmol methacrylate were excreted in the urine within 24 hr of exposure. Since there was no measurement of the exposure concentration in this study, it was impossible to make a correlation between exposure and urinary levels. Excreted methacrylate concentrations showed a wide interindividual variability and were not consistently related to exposure time. The authors state that inhalation exposure would not give the observed methacrylate urine levels due to the usually low workplace concentrations in dental laboratories. Air levels were not determined in the study however.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

69名接受髋关节置换术的患者，约接受了48克半固化甲基丙烯酸酯骨水泥，分别于植入后10、30、60、120秒，3、4、5、6、8、10分钟采集血样。患者之间的单体浓度差异很大。最大血药浓度在植入后30至60秒之间获得，平均浓度为0.8 - 1.2微克/毫升。获得的最高浓度为16微克/毫升。在3分钟和6分钟后采集的样本中，未检测到MMA。

Blood samples of 69 patients with a hip arthroplasty, receiving about 48 g of a half-cured methacrylate bone cement, were taken 10, 30, 60, and 120 sec, 3 ,4, 5, 6, 8, and 10 min after the implantation. Concentrations of the monomer varied widely between the patients. Maximum blood levels were obtained between 30 and 60 sec after implantation, with mean concentrations of 0.8 - 1.2 ug/mL. The highest concentration obtained was 16 ug/mL. In samples taken after 3 and 6 min, no MMA could be detected.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

11名接受使用基于MMA的骨水泥的关节假体的患者的静脉和动脉血样本在将骨水泥引入髋臼窝或股骨后0.5、1、1.5、2、3、4、5、6和7分钟时采集。通过气相色谱法分析样本中的MMA含量。当将骨水泥引入髋臼窝后，静脉血中的水平高于骨水泥应用于股骨时的水平。动脉血中的水平显著低于静脉血。静脉血中MMA浓度最高（> 1 ug/mL）在暴露后1.4分钟达到。MMA的消除遵循双指数动力学，初始半衰期为0.3分钟，终末半衰期为3分钟。

Samples of venous and arterial blood of 11 patients receiving joint prostheses using MMA based bone cement were taken 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 7 min after introduction of the bone cement either into the cotyloid cavity or into the femur. The samples were analyzed for MMA content by GC. After introducing the bone cement into the cotyloid cavity, venous blood levels were higher than when the bone cement was applied to the femur. Arterial blood levels were significantly lower than venous blood levels. The highest MMA concentrations in venous blood (> 1 ug/mL) were reached 1.4 min after exposure. The elimination of MMA followed biexponential kinetics with an initial half-life of 0.3 min and a terminal half-life of 3 min.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露等级：
  A
• 职业暴露限值：
  TWA: 100 ppm (410 mg/m3)
• TSCA：
  Yes
• 危险等级：
  3
• 立即威胁生命和健康浓度：
  1,000 ppm
• 危险品标志：
  F
• 安全说明：
  S24,S37,S46
• 危险类别码：
  R43,R11,R37/38
• WGK Germany：
  1
• 海关编码：
  3824909990
• 危险品运输编号：
  UN 1247
• RTECS号：
  OZ5075000
• 包装等级：
  II
• 储存条件：
  储存注意事项：通常商品会添加阻聚剂。应将物品存放于阴凉、通风的库房中，远离火种和热源，并避免阳光直射。库温不宜超过37℃。包装需密封，不可与空气接触。与氧化剂、酸类、碱类、卤素等物质要分开存放，切忌混储。不宜大量储存或长期存放。照明和通风设施应采用防爆型，禁止使用易产生火花的机械设备和工具。储存区域应配备泄漏应急处理设备及合适的收容材料。

SDS

国标编号:	32149
ＣＡＳ:	80-62-6
中文名称:	甲基丙烯酸甲酯
英文名称:	Methyl methacrylate；Methacrylic acid，methyl ester
别 名:	异丁烯酸甲酯；牙托水；有机玻璃单体
分子式:	C 5 H 8 O 2 ；CH 2 C(CH 3 )COOCH 3
分子量:	100.12
熔 点:	-50℃ 沸点：101℃
密 度:	相对密度(水=1)；相对
蒸汽压:	10℃
溶解性:	微溶于水，溶于乙醇等
稳定性:	稳定
外观与性状:	无色易挥发液体，并具有强辣味
危险标记:	7(易燃液体)
用 途:	用作有机玻璃的单体，也用于制造其它树脂、塑料、涂料、粘合剂、润滑剂

2.对环境的影响:
一、健康危害
侵入途径：吸入、食入。
健康危害：人对本品气味感觉阈浓度为85mg/m ³ ，刺激作用阈浓度(暴露1分钟)为285mg/m ³ 。中毒表现为乏力、恶心、反复呕吐、头痛、头晕、胸闷、伴有短暂的意识消失、中性白细胞增多症。慢性中毒：神经系统受损的综合症状占主要地位，个别可发生中毒性脑病。可引起轻度皮炎和结膜炎。接触时间长可致麻醉作用。
二、毒理学资料及环境行为
毒性：为麻醉剂，麻醉浓度和致死浓度几乎相同，有弱的刺激作用。
急性毒性：LD ₅₀ 7872mg/kg(大鼠经口)；LC ₅₀ 3750ppm(大鼠吸入)；人吸入725ppm，最小致死浓度；人吸入62ppm×20～90分钟，粘膜刺激；人吸入12.5～25ppm×20～90分钟，头晕，恶心，意识障碍。
亚急性和慢性毒性：狗吸入46800ppm×1.5小时/日×8日，绝对致死浓度，肝、肾有损害。
致突变性：微粒体致突变：鼠伤寒沙门氏菌34mmol/L。
生殖毒性：大鼠吸入最低中毒浓度(TCL ₀ )：109g/kg(孕6～15天用药)，致胚胎毒性，对肌肉骨骼系统有影响。
危险特性：遇明火、高热或与氧化剂接触，有引起燃烧爆炸的危险。若遇高热，可能发生聚合反应，出现大量放热现象，引起容器破裂和爆炸事故。其蒸气比空气重，能在较低处扩散到相当远的地方，遇明火会引着回燃。
燃烧(分解)产物：一氧化碳、二氧化碳。

3.现场应急监测方法:

4.实验室监测方法:

气相色谱法《空气中有害物质的测定方法》，杭士平主编
羟胺-氯化铁比色法《空气中有害物质的测定方法》，杭士平主编

5.环境标准:

前苏联	车间空气中有害物质的最高容许浓度	10 mg/m 3
前苏联(1975)	居民区大气中有害物最大允许浓度	0.1mg/m 3 (最大值，昼夜均值)
前苏联(1975)	水体中有害有机物的最大允许浓度	0.01mg/L
	嗅觉阈浓度	0.21ppm

6.应急处理处置方法:

一、泄漏应急处理
切断火源。戴自给式呼吸器，穿一般消防防护服。在确保安全情况下堵漏。喷水雾可减少蒸发。用砂土、蛭石或其它惰性材料吸收，然后运至空旷的地方掩埋、蒸发、或焚烧。或用不燃性分散剂制成的乳液刷洗，经稀释的洗液放入废水系统。如大量泄漏，利用围堤收容，然后收集、转移、回收或无害处理后废弃。
二、防护措施
呼吸系统防护：空气中浓度较高时，建议佩戴防毒面具。
眼睛防护：戴化学安全防护眼镜。
防护服：穿防静电工作服。
手防护：必要时戴防护手套。
其它：工作现场严禁吸烟。工作后，淋浴更衣。注意个人清洁卫生。
三、急救措施
皮肤接触：脱去污染的衣着，用肥皂水及清水彻底冲洗。
眼睛接触：立即翻开上下眼睑，用流动清水冲洗15分钟。就医。
吸入：脱离现场至空气新鲜处。呼吸困难时给输氧。呼吸停止时，立即进行人工呼吸。
食入：误服者给饮足量温水，催吐，就医。

灭火方法：雾状水、泡沫、二氧化碳、干粉、砂土。

制备方法与用途

聚甲基丙烯酸酯简介

聚甲基丙烯酸酯，全称聚甲基丙烯酸甲酯（Polymethacrylates，PMMA），是一种重要的光学透明塑料。它具有高透明度、优良的耐冲击性能、轻质、经济实惠及环保无毒等优点，广泛用作玻璃替代材料。最显著的特点是其优异的光学性能，这也导致了它俗称“有机玻璃”的原因。由于它是无定型聚合物，分子排列均匀不会影响光线在内部各部分通过的速度，使得光线下行畅通无阻。

然而，尽管拥有诸多优点，PMMA也存在表面硬度低、耐磨性差以及容易受到化学溶剂侵蚀等缺点。因此，在使用之前通常需对其进行一定的表面处理以达到扬长避短的效果。

PMMA的表面改性

PMMA进行表面改性的常用方法是涂覆一层耐磨加硬材料。常见的塑料耐磨加硬材料可以分为两大类：一类是以多官能度丙烯酸酯为主体的紫外光固化硬质涂层体系；另一类则是以聚硅氧烷预聚体为主的热固型有机硅硬质涂层体系。

• 紫外光固化硬质涂层体系的优势在于固化速度快，适合流水线作业。不过，它的缺点是涂层容易老化，并且对紫外线和高温敏感。
• 热固型有机硅涂层虽然固化速度较慢，但其机械性能更稳定、耐热性更好。

生产方法

PMMA的生产可通过多种途径进行：

1. 丙酮氰醇法：首先将丙酮与氰化氢反应生成丙酮氰醇，随后与硫酸及甲醇反应制得甲基丙烯酸甲酯。
2. 丙烯法：丙烯、一氧化碳和甲醇通过羰化反应合成中间体，再将其分解成目标产物。
3. 异丁烯法：在钼催化剂存在下用空气对异丁烯进行两段氧化，生成甲基丙烯酸甲酯。
4. 一步氧化法：以杂多酸及其盐类为催化剂，直接将异丁醛氧化生成甲基丙烯酸，再与甲醇反应制得目标产物。

物理化学性质

• 分类：易燃液体
• 毒性分级：中毒
  • 口服LD50（大鼠）:7872 mg/kg；口服LD50（小鼠）:3625 mg/kg
• 刺激数据：
  • 眼睛刺激：兔子 150 mg
  • 皮肤刺激：兔子 10,000 mg/kg
• 爆炸物危险特性：与空气混合可爆
• 可燃性危险特性：遇明火、高温或氧化剂易燃；燃烧时产生刺激烟雾
• 储运特性：应储存在通风良好且低温干燥的地方，避免与酸类及氧化剂接触

灭火方法

• 干粉灭火器

• 雾状水

• 二氧化碳灭火器

• 泡沫灭火器

• 职业暴露限值：

  • 时间加权平均容许浓度（TWA）：410 mg/m³
  • 短时间接触极限（STEL）：615 mg/m³

反应信息

• 作为反应物：
  描述：

  甲基丙烯酸甲酯 在 K₃HCo(CN)5 、 β-环糊精 氢氧化钾 、 氢气 作用下， 反应 24.0h， 以87%的产率得到异丁酸
  参考文献：
  名称：

  β-cyclodextrin and hydridopentacyanocobaltate catalyzed selective hydrogenation of α,β,-unsaturated acids and their derivatives

  摘要：

  DOI：

  10.1016/s0040-4039(00)88883-8
• 作为产物：
  描述：

  丙酮氰醇 在 硫酸 作用下， 以 水 为溶剂， 以93.4%的产率得到甲基丙烯酸甲酯
  参考文献：
  名称：

  METHOD FOR HYDROLYSING ACETONE CYANOHYDRIN

  摘要：

  本发明涉及一种通过硫酸对丙酮氰醇（ACH）进行水解的过程，用于制备甲基丙烯酸（MAA）或甲基丙烯酸甲酯（MMA）的ACH磺酸法过程。

  公开号：

  US20150045577A1
• 作为试剂：
  描述：

  2,2,6,6-四甲基哌啶氧化物 、 4-甲苯硫酚 在 甲基丙烯酸甲酯 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 1.0h， 生成 2,2,6,6-tetramethyl-1-((p-tolylthio)oxy)piperidine
  参考文献：
  名称：

  Auto-oxidative hydroxysulfenylation of alkenes

  摘要：

  一锅法介导的电子不足和电子富集烯烃与苯硫醇的羟基硫醚化反应被探索。

  DOI：

  10.1039/c6cc01937d

文献信息

• [EN] BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS<br/>[FR] ANALOGUES D’ARYLSPHINGOSINE-1-PHOSPHATE BICYCLIQUES
  申请人：BIOGEN IDEC INC

  公开号：WO2011017561A1

  公开（公告）日：2011-02-10

  Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.

  提供具有在一个或多个SlP受体上拮抗活性的化合物。这些化合物是鞘氨醇类似物，在磷酸化后可以在SlP受体上表现为拮抗剂。
• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• Total Synthesis of Hybocarpone and Analogues Thereof. A Facile Dimerization of Naphthazarins to Pentacyclic Systems
  作者：K. C. Nicolaou、David L. F. Gray

  DOI：10.1021/ja030497n

  日期：2004.1.1

  The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compounds is described. The successful route to hybocarpone features a novel radical-based dimerization/hydration cascade which generates the bridging hindered carbon-carbon bond of the molecule in a stereocontrolled manner, setting the relative configurations of the four contiguous stereocenters in a single step

  描述了地衣衍生的抗肿瘤剂 Hybocarpone (1) 和相关化合物的全合成。Hybocarpone 的成功途径具有一种新型的基于自由基的二聚化/水合级联，它以立体控制的方式产生分子的桥接受阻碳 - 碳键，在一个步骤中设置四个连续立体中心的相对构型。推测该过程可能与导致自然界中hybocarpone形成的生物合成途径没有太大不同。这些分子框架的开发序列还具有合成有用的 Diels-Alder 捕获光化学生成的羟基-o-醌二甲烷物种与 1,1-二取代烯烃以形成季中心的第一个例子，
• Ultra‐High‐Molecular‐Weight Polymers Produced by the Immortal Phosphine‐Based Catalyst System
  作者：Yun Bai、Jianghua He、Yuetao Zhang

  DOI：10.1002/anie.201811946

  日期：2018.12.21

  promote the frustrated Lewis pair (FLP)‐catalyzed living polymerization of methyl methacrylate (MMA), achieving ultrahigh molecular weight (UHMW) poly(methyl methacrylate) (PMMA) with Mn up to 1927 kg mol−1 and narrow molecular weight distribution (MWD) at room temperature (RT). This FLP catalyst system exhibits exceptionally long lifetime polymerization performance even in the absence of free MMA, which

  强大的有机磷超碱N-（二苯基膦基）-1,3-二异丙基-4,5-二甲基-1,3-二氢-2H-咪唑-2-亚胺（IAP3）与位阻但适度为酸性的路易斯酸结合使用（LA），（4-Me- 2,6 - t Bu 2 -C 6 H 2 O）Al i Bu 2（（BHT）Al i Bu 2），以协同促进沮丧的Lewis对（FLP）催化的生活聚合甲基丙烯酸甲酯（MMA），实现M n高达1927 kg mol -1的超高分子量（UHMW）聚甲基丙烯酸甲酯（PMMA）和在室温（RT）下较窄的分子量分布（MWD）。该FLP催化剂体系即使在不存在游离MMA的情况下，也表现出异常长的聚合寿命，这可以在将所得体系在室温下放置24小时后重新引发所需的活性聚合。
• Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters
  作者：Alistair J. M. Farley、Christopher Sandford、Darren J. Dixon

  DOI：10.1021/jacs.5b10226

  日期：2015.12.30

  The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Brønsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a

  描述了在温和条件下由双功能亚氨基正膦有机催化剂催化的烷基硫醇与未活化的 α-取代丙烯酸酯的高度对映选择性磺基-迈克尔加成反应。催化剂亚氨基正膦部分的强布朗斯台德碱性为烷基硫醇亲核试剂提供了必要的活化，而中央硫脲氢键供体侧翼的两个叔亮氨酸残基促进了瞬态烯醇中间体质子化过程中的高对映选择性. 该反应在烷基硫醇、酯部分和 α,β-不饱和酯的 α-取代基方面的范围很广，以优异的产率（高达 >99%）和对映选择性（高达到 96% ee)，并且可以使用低至 0 的催化剂负载量进行十克放大。

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