羟基乙酸 | 79-14-1

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 中文名称: 羟基乙酸
• 中文别名: 羟基醋酸；乙醇酸；A-羟基羧酸；甘醇酸；AHA-甘醇酸
• 英文名称: Glycolic Acid
• 英文别名: 2-hydroxyacetic acid；hydroxyacetic acid；glycollic acid；2-Oxonioacetate
• CAS: 79-14-1
• 化学式: C₂H₄O₃
• mdl: MFCD00004312
• 分子量: 76.052
• InChiKey: AEMRFAOFKBGASW-UHFFFAOYSA-N

物化性质

• 熔点：
  75-80 °C (lit.)
• 沸点：
  112 °C
• 密度：
  1.25 g/mL at 25 °C
• 闪点：
  112°C
• 溶解度：
  H2O：0.1 g/mL，澄清
• LogP：
  -1.07 at 20℃
• 物理描述：
  Solid
• 颜色/状态：
  Colorless, translucent solid
• 气味：
  Odorless
• 蒸汽密度：
  Relative vapor density (air = 1): 2.6
• 蒸汽压力：
  2.0X10-2 mm Hg at 25 °C (extrapolated)
• 亨利常数：
  Henry's Law constant = 8.5X10-8 atm-cu m/mol at 25 °C (est)
• 稳定性/保质期：
  1. 无色结晶，易潮解。 2. 纯品毒性较低，但因其为强酸，具有刺激性。与皮肤接触会引起严重肿痛。大鼠经口LD50值为1950 mg/kg。现场操作人员需穿戴好防护用具，生产设备应严格密闭，并确保工作场所具备良好的通风条件。 3. 该物质存在于烤烟和白肋烟的烟叶中以及烟气中。
• 分解：
  100 °C
• 腐蚀性：
  Corrosive
• 燃烧热：
  -697.23 kJ/mole
• 解离常数：
  pKa = 3.83 at 25 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

口服给予的乙二醇（EG）及其主要代谢物甘醇酸（GA）和草酸（OX）在怀孕（P；给药时怀孕第10天，GD 10）大鼠体内的动力学进行了比较，并且比较了怀孕和非怀孕（NP）大鼠之间的差异。将4组颈静脉插管雌性大鼠分别给予10（P和NP）、150（P）、500（P）、1000（P）或2500（P和NP）mg（13）C标记的EG/kg体重。在给药后24小时内定期收集血液样本和尿液，并使用GC/MS技术分析EG、GA和OX。确定了EG和GA的药代动力学参数，包括Cmax、Tmax、AUC和beta-t(1/2)。怀孕状态（GD 10-11）对所研究的药代动力学参数没有影响。血液中GA的水平在大约10到150 mg EG/kg的剂量范围内呈剂量比例增加，但从500到1000 mg EG/kg的剂量增加不成比例。当剂量大于或等于500 mg EG/kg时，EG和GA表现出剂量依赖性的尿液消除，这可能是由于EG到GA的代谢转化以及GA到下游代谢物的转化达到饱和。非线性动力学的转变涵盖了大鼠EG发育毒性的NOEL（500 mg EG/kg）和LOEL（1000 mg EG/kg），为GA在EG发育毒性中的作用提供了额外的证据。与大鼠EG发育毒性LOEL相关的母体血液中GA的峰值浓度相当高（363微克/克或4.8 mM血液）。在所有剂量水平下，OX在血液和尿液中的含量都非常低，这表明OX对EG发育毒性并不重要。

The kinetics of orally administered ethylene glycol (EG) and its major metabolites, glycolic acid (GA) and oxalic acid (OX), in pregnant (P; gestation day 10 at dosing, GD 10) rats were compared across doses, and between pregnant and nonpregnant (NP) rats. Groups of 4 jugular vein-cannulated female rats were administered 10 (P and NP), 150 (P), 500 (P), 1000 (P), or 2500 (P and NP) mg (13)C-labelled EG/kg body weight. Serial blood samples and urine were collected over 24-hr postdosing, and analyzed for EG, GA, and OX using GC/MS techniques. Pharmacokinetic parameters including Cmax, Tmax, AUC, and beta-t(1/2) were determined for EG and GA. Pregnancy status (GD 10-11) had no impact on the pharmacokinetic parameters investigated. Blood levels of GA were roughly dose-proportional from 10 to 150 mg EG/kg, but increased disproportionately from 500 to 1000 mg EG/kg. EG and GA exhibited dose-dependent urinary elimination at doses > or = 500 mg EG/kg, probably due to saturation of metabolic conversion of EG to GA, and of GA to downstream metabolites. The shift to nonlinear kinetics encompassed the NOEL (500 mg EG/kg) and LOEL (1000 mg EG/kg) for developmental toxicity of EG in rats, providing additional evidence for the role of GA in EG developmental toxicity. The peak maternal blood concentration of GA associated with the LOEL for developmental toxicity in the rat was quite high (363 microg/g or 4.8 mM blood). OX was a very minor metabolite in both blood and urine at all dose levels, suggesting that OX is not important for EG developmental toxicity.

来源:Hazardous Substances Data Bank (HSDB)

代谢

二氯乙酸（DCA）在Fischer 344大鼠体内的处置情况进行了研究，研究是在大鼠口服灌胃282 mg/kg的1-或2-(14C)DCA（1-DCA或2-DCA）以及28.2 mg/kg的2-DCA后48小时内进行的。主要的尿液代谢物是甘油酸、乙醛酸和草酸。DCA及其代谢物在组织中积累，并且缓慢排出体外...

The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 hr after oral gavage of 282 mg/kg of 1- or 2-(14C)DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA... The major urinary metabolites were glycolic acid, glyoxylic acid, and oxalic acid. DCA and its metabolites accumulated in the tissues and were eliminated slowly....

来源:Hazardous Substances Data Bank (HSDB)

代谢

乙二醇（EG）和草酸的积累以及消除动力学在雄性Sprague-Dawley大鼠和混合品种狗中进行了检查...。通过灌胃给药...。EG的血药浓度峰值出现在给药后2小时，而草酸的峰值出现在4-6小时之间。大鼠中EG的消除速率稍快，半衰期为1.7小时，而狗的半衰期为3.4小时。大鼠中草酸的最大血浆水平更高，尽管其积累模式与狗相似。草酸从血浆中消失的时间与EG相同，这表明代谢物的消除速率比EG慢。肾脏排泄是EG消除的重要途径，占总剂量的20-30%。草酸的肾脏排泄约占剂量的5%... /草酸/

The accumulation of glycolate and the elimination kinetics of ethylene glycol (EG) /was examined in/ ... male Sprague-Dawley rats and mixed breed dogs... . EG was administered by gavage ... . The peak plasma level of EG occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of EG elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats, although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as EG, suggesting a slower rate of elimination of the metabolite than that of EG. Renal excretion of EG was an important route for its elimination, accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose... /Glycolate/

来源:Hazardous Substances Data Bank (HSDB)

代谢

1,2-(14)C-Ethylene glycol (EG) was given to female CD (Sprague-Dawley) rats and CD-1 mice in order to determine tissue distribution and metabolic fate after intravenous (iv), peroral (po), and percutaneous (pc) doses. Rats were given doses of 10 or 1000 mg/kg by each route, and additional pc doses of 400, 600 or 800 mg/kg. Mice were also given iv and po doses of 10 or 1000 mg/kg, and intermediate po doses of 100, 200 or 400 mg/kg. Mice were given po doses of 100 or 1000 mg/kg, and both species were given a 50% (w/w) aqueous po dose to simulate antifreeze exposure. For both species, EG is very rapidly and almost completely adsorbed after po doses. ... The tissue distribution of EG following either iv or po routes was essentially the same, with similar percentages recovered for each dose by both routes and for either species. Cutaneously-applied EG was slowly and rather poorly adsorbed in both species, in comparison with po-dose administration, and urinalysis after undiluted po doses indicated that EG probably penetrates rat skin in the parent form. There was an absence in both species of dose-dependent changes in disposition and elimination following the pc application of EG. (14)C-labelled EG, glycolic acid and/or oxalic acid accounted for the majority of the detectable radioactivity in the urine samples from all dose routes in the rat, while glycoaldehyde and glyoxylic acid were not detected in any of the urine fractions evaluated. Similar increases in glycolate production with increasing dose were also observed in mouse urine samples from iv and po dosing. Also, glyoxylate and oxalate were absent from mouse urine... 给雌性CD（Sprague-Dawley）大鼠和CD-1小鼠注射了1,2-(14)C-乙二醇（EG），以确定在静脉（iv）、口服（po）和经皮（pc）给药后EG的组织分布和代谢命运。大鼠通过每种途径接受了10或1000毫克/千克的剂量，以及额外的400、600或800毫克/千克的pc剂量。小鼠也接受了10或1000毫克/千克的iv和po剂量，以及100、200或400毫克/千克的中间po剂量。小鼠接受了100或1000毫克/千克的po剂量，并且两种物种都接受了50%（w/w）的水性po剂量以模拟防冻液暴露。对于两种物种，EG在po剂量后非常迅速并且几乎完全被吸收。...无论是iv还是po途径，EG的组织分布基本上是相同的，每种剂量通过两种途径和两种物种都回收了相似百分比。与po剂量给药相比，皮肤应用的EG在两种物种中都是缓慢且相当差地被吸收，并且未稀释po剂量后的尿液分析表明EG可能以母体形式穿透大鼠皮肤。在两种物种中，pc应用EG后，处置和消除没有剂量依赖性的变化。(14)C标记的EG、甘醇酸和/或草酸酸占了大鼠所有给药途径尿液中可检测放射性的大部分，而在评估的所有尿液馏分中都没有检测到甘醇醛和甘氧酸。随着剂量的增加，小鼠iv和po给药的尿液中甘醇酸盐的产生也观察到类似的增加。此外，小鼠尿液中没有检测到甘氧酸和草酸盐...

1,2-(14)C-Ethylene glycol (EG) was given to female CD (Sprague-Dawley) rats and CD-1 mice in order to determine tissue distribution and metabolic fate after intravenous (iv), peroral (po), and percutaneous (pc) doses. Rats were given doses of 10 or 1000 mg/kg by each route, and additional pc doses of 400, 600 or 800 mg/kg. Mice were also given iv and po doses of 10 or 1000 mg/kg, and intermediate po doses of 100, 200 or 400 mg/kg. Mice were given po doses of 100 or 1000 mg/kg, and both species were given a 50% (w/w) aqueous po dose to simulate antifreeze exposure. For both species, EG is very rapidly and almost completely adsorbed after po doses. ... The tissue distribution of EG following either iv or po routes was essentially the same, with similar percentages recovered for each dose by both routes and for either species. Cutaneously-applied EG was slowly and rather poorly adsorbed in both species, in comparison with po-dose administration, and urinalysis after undiluted po doses indicated that EG probably penetrates rat skin in the parent form. There was an absence in both species of dose-dependent changes in disposition and elimination following the pc application of EG. (14)C-labelled EG, glycolic acid and/or oxalic acid accounted for the majority of the detectable radioactivity in the urine samples from all dose routes in the rat, while glycoaldehyde and glyoxylic acid were not detected in any of the urine fractions evaluated. Similar increases in glycolate production with increasing dose were also observed in mouse urine samples from iv and po dosing. Also, glyoxylate and oxalate were absent from mouse urine...

来源:Hazardous Substances Data Bank (HSDB)

代谢

羟基乙酸的降解主要途径是转化为乙醛酸。这一反应由乳酸脱氢酶或羟基酸氧化酶催化。一旦形成乙醛酸，它就会被迅速降解为多种产物，其中只有少数被观察到。人们认为，乙醛酸分解为2-羟基-3-氧代戊酸的过程是由硫胺素焦磷酸在镁离子存在下催化的。甘氨酸的形成涉及吡哆醛磷酸和乙醛酸转氨酶，而通过甲酸形成二氧化碳和水的过程显然涉及辅酶A（CoA）和黄素单核苷酸。

The main path of the degradation of glycolic acid is to glyoxylic acid. This reaction is mediated by lactic dehydrogenase or glycolic acid oxidase. Once glyoxylic acid is formed, it is apparently degraded very rapidly to a variety of products, a few of which have been observed. Its breakdown to 2-hydroxy-3-oxoadipate it is thought, is mediated by thiamine pyrophosphate in the presence of magnesium ions. The formation of glycine involves pyridoxal phosphate and glyoxylate transaminase, whereas the formation of carbon dioxide and water via formic acid apparently involves coenzyme A (CoA) and flavin mononucleotides. (T29)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

识别和使用：羟基乙酸（甘醇酸）是一种无色、无味、半透明的固体。羟基乙酸的主要用途在于清洁和金属加工。其它专业应用包括生物医疗用途、印刷线路板助焊剂、粘合剂、纺织品、硫化氢减排、制革、油井酸化以及用于可吸收缝合线和药物传递系统的可生物降解聚合物和共聚物。它还用于护肤品中作为去角质和角质软化剂。人类暴露和毒性：吸入可能会引起鼻咽粘膜刺激，以及上呼吸道和支气管刺激。皮肤接触可能会导致严重的皮肤刺激，伴有不适或皮疹。高浓度或长期暴露可能会导致皮肤烧伤或溃疡。眼睛接触可能会导致眼睛腐蚀，伴有角膜或结膜溃疡。可能会发生永久性眼睛损伤。摄入可能会导致粘膜腐蚀，伴有胃部不适、恶心和虚脱。严重过度暴露可能会导致肾脏损伤或死亡。动物毒性研究：在大鼠基础饲料中添加3%的甘醇酸，持续3周，导致草酸尿石症（大部分在肾脏中，但有些动物在输尿管和膀胱中也有尿石。此外，皮质和髓质中存在细小的结晶沉积，肾乳头表面或嵌入肾乳头的聚集体。在每天口服1000毫克甘醇酸的狗中，未发现异常的草酸分泌，也未报告胃肠道或肾脏损伤。在另一项实验中，大鼠通过灌胃的方式给予高达600毫克/千克/天的测试物质，持续90天。在600毫克/千克/天的雄性中发生了两起死亡。300和600毫克/千克/天组的雄性和雌性体重下降、总体体重增加、食物消耗和食物效率降低。在300和600毫克/千克/天剂量水平下，仅在雄性中观察到草酸结晶性肾病变和不正常的肾积水以及肾盂过渡上皮细胞增生的显微发现。在暴露于300或600毫克/千克/天的雌性大鼠中，没有观察到表明系统毒性的器官重量、肉眼或显微发现。在大鼠怀孕的第7-21天评估了甘醇酸的发展毒性。将交配的雌性大鼠按每天剂量高达600毫克/千克进行灌胃。在600毫克/千克时，明显显示了母体毒性。在600毫克/千克时，明显显示了发展毒性。平均胎儿体重统计学显著降低，而骨骼（肋骨、脊椎和胸骨）畸形和变异的发生率统计学显著增加。基于使用Salmonella typhimurium TA98、TA100、TA1535、TA1537和TA1538进行激活和未激活的Ames试验阴性结果，未发现甘醇酸具有基因毒性。生态毒性研究：绿藻暴露于甘醇酸72小时。在暴露期结束时，选择一个对照组和显示细胞计数抑制50%或以上的测试浓度的样本进行恢复测试，并将它们暴露于营养培养基额外144小时。对生长速率和生物量的影响被发现是抗藻性的。在静态条件下，将胖头鱼暴露于甘醇酸96小时。所有死亡发生在24小时内。在静态条件下，将水蚤暴露于甘醇酸48小时。在存活的水蚤中没有观察到亚致死效应。

IDENTIFICATION AND USE: Hydroxyacetic (glycolic) acid is an odorless, colorless and translucent solid. The primary uses of hydroxyacetic acid are in cleaning and metal processing. Other specialized applications include biomedical uses, printed wire board flux, adhesives, textiles, hydrogen sulfide abatement, tanning, oil well acidification, and biodegradable polymers and copolymers for absorbable sutures and drug delivery systems. It is also used in skin care products as exfolliant and keratolytic. HUMAN EXPOSURE AND TOXICITY: Inhalation may cause irritation of mucous membranes with upper respiratory and bronchial irritation. Skin contact may cause severe skin irritation with discomfort or rash. Higher or prolonged exposure may cause skin burns or ulceration. Eye contact may cause eye corrosion with corneal or conjunctival ulceration. Permanent eye damage can occur. Ingestion may cause corrosion of mucous membranes with stomach discomfort, nausea, and prostration. Kidney damage or fatality may occur from gross overexposure. ANIMAL TOXICITY STUDIES: A basal diet with 3% glycolic acid for 3 weeks in rats resulted in a high incidence of oxalate urolithiasis (mostly in the kidneys, but some animals also had uroliths in the ureter and urinary bladder. Also, fine crystalline depositions were present throughout the cortex and medulla and clusters of concretions were on the surface or embedded in the renal papilla. In dogs given daily oral doses of 1000 mg glycolic acid for 35 days, no abnormal secretions of oxalic acid were found and no damage to the gastroenteric tract or kidneys was reported. In other experiment, rats were administered up to 600 mg/kg/day of the test substance by gavage for 90 days. Two deaths occurred in males at 600 mg/kg/day. Decreased mean body weight, overall body weight gain, food consumption, and food efficiency occurred in males and females of the 300 and 600 mg/kg/day groups. Microscopic findings of oxalate crystal nephrosis and unilateral hydronephrosis, and hyperplasia of the transitional epithelium of the renal pelvis were also observed (in males only) at these dose levels. No organ weight, gross or microscopic findings indicative of systemic toxicity were observed in female rats exposed to 300 or 600 mg/kg/day. The developmental toxicity of glycolic acid was assessed in rats over days 7-21 of gestation. Groups of mated female rats were gavaged at daily dose levels of up to 600 mg/kg. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg. There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. Glycolic acid was not found to be genotoxic based on negative Ames test with and without activation using Salmonella typhimurium TA98, TA100, TA1535, TA1537, and TA1538. ECOTOXICITY STUDIES: Green Algae were exposed to glycolic acid for 72 hours. At the end of the exposure period, a control replicate and samples from the test concentrations exhibiting a 50% or greater inhibition of cell counts were selected for a recovery test and exposed to nutrient medium for an additional 144 hours. The effects upon growth rate and biomass were found to be algistatic. Fathead minnows were exposed to glycolic acid for 96 hours under static conditions. All deaths occurred within 24 hours. Daphnia magna were exposed to glycolic acid for 48 hours under static conditions. There were no sublethal effects observed in the surviving daphnids.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

乙酸的毒性是由于其代谢成草酸。乙酸和草酸，以及过量的乳酸，是导致阴离子间隙代谢性酸中毒的原因。草酸容易与钙反应形成不溶性的草酸钙晶体。组织损伤是由草酸晶体的广泛沉积和乙酸的毒性作用引起的。（A612, A613）

Glycolic acid's toxicity is due to its metabolism to oxalic acid. Glycolic and oxalic acid, along with excess lactic acid, are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic acid. (A612, A613)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

丙酸代谢成草酸，草酸与钙反应，在肾脏形成草酸钙晶体。这可能导致肾脏损伤，进而引发急性肾功能衰竭。(L1023) 慢性高丙酸水平与I型原发性高草酸尿症的代谢先天错误有关。原发性高草酸尿症中的草酸结石往往很严重，导致相对较早的肾脏损伤（20岁之前），这损害了草酸的排泄，导致体内草酸积累加速。肾功能衰竭后，患者可能会在骨骼、关节和骨髓中发展草酸沉积。严重病例可能会出现血液学问题，如贫血和血小板减少症。体内的草酸沉积有时被称为“草酸症”，以区别于“草酸尿”，后者指的是尿液中的草酸。

Glycolic acid metabolizes to oxalic acid, which reacts with calcium and forms calcium oxalate crystals in the kidney. This can cause kidney injury, leading to acute kidney failure. (L1023) Chronically high levels of glycolic acid are associated with the inborn error of metabolism known as Type I primary hyperoxaluria. Oxalate stones in primary hyperoxaluria tend to be severe, resulting in relatively early kidney damage (before age 20), which impairs the excretion of oxalate leading to a further acceleration in accumulation of oxalate in the body. After the development of renal failure patients may develop oxalate deposits in the bones, joints and bone marrow. Severe cases may develop haematological problems such as anaemia and thrombocytopaenia. The deposition of oxalate in the body is sometimes called "oxalosis" to be distinguished from "oxaluria" which refers to oxalate in the urine.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：目前没有关于在母乳喂养期间将甘醇酸（羟基乙酸）涂于皮肤的临床使用信息。由于它不太可能被显著吸收或出现在母乳中，因此被认为在母乳喂养期间使用是安全的。避免涂抹在可能与婴儿皮肤直接接触的身体部位，或婴儿可能通过舔食摄入药物的部位。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the clinical use of glycolic acid (hydroxyacetic acid) on the skin during breastfeeding. Because it is unlikely to be appreciably absorbed or appear in breastmilk, it is considered safe to use during breastfeeding. Avoid application to areas of the body that might come in direct contact with the infant's skin or where the drug might be ingested by the infant via licking. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

10%的水合甘醇酸透过率，通过使用氨水或氢氧化钠调节pH值至3.8，利用分离的尤卡坦迷你猪表皮和无毛小鼠全层皮肤进行了检测。每个配方的200微升样品被施加到Franz扩散池的区域内，并通过液闪计数法分析甘醇酸。在使用封闭贴片的情况下，渗透是线性的，滞后时间小于15毫米。8小时后，分别有0.8%和1.6%的氨水和钠盐透过猪皮模型，分别有1.8%和2.3%的氨水和钠盐透过小鼠皮肤模型。在开放式贴片条件下，渗透不是线性的，滞后时间大于15毫米。使用猪皮模型，分别有1.1%和0.7%的氨水和钠盐透过，使用小鼠皮肤模型，分别有0.6%和0.9%的氨水和钠盐透过。

The penetration of 10% aq. glycolic acid, adjusted to pH 3.8 using either ammonium or sodium hydroxide, was examined using separated Yucatan minipig epidermis and full thickness hairless mouse skin. A 200 uL-aliquot of each formulation was applied to an area of a Franz diffusion cell, and glycolic acid was analyzed using liquid scintillation counting. Using an occlusive patch, penetration was linear with a lag time of less than 15 mm. After 8 hr, 0.8 and 1.6% of the ammonium and sodium salts penetrated, respectively, using the pig skin model and 1.8 and 2.3% of the ammonium and sodium salts penetrated, respectively, using the mouse skin model. Under open patch conditions, penetration was not linear and lag time was greater than 15 mm. Using the pig skin model, 1.1 and 0.7% of the ammonium and sodium salts penetrated, respectively, and using the mouse skin model, 0.6 and 0.9% of the ammonium and sodium salts penetrated, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

使用一种体外系统研究了（14）C-甘醇酸的皮肤渗透，该系统中，将一种乳膏配方涂抹在猪皮上，剂量为5毫克/0.79平方厘米皮肤，不使用封闭贴片。确定有3.1%的甘醇酸渗透进皮肤。

The skin penetration of (14)C-glycolic acid was studied using an in vitro system in which a cream formulation was applied to pig skin at a dose of 5 mg/0.79 sq cm skin without an occlusive patch. It was determined that 3.1% of the applied glycolic acid penetrated the skin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

两只雌性恒河猴通过胃管口服了4 mL/kg的500 mg/kg均质1-(14)C-乙醇酸，0.73 uC/mmol，在水中溶液。在0-8、8-24、24-48、48-72小时的时间间隔内收集尿液，对于一只猴子，还收集了72-96小时的尿液。在72小时内，一只动物排出了剂量的53.2%（14）C，其中51.4%通过尿液排出；51.4%的剂量在前24小时内排出。第二只动物在96小时内总共排出了42.2%（14）C，其中36.6%通过尿液排出；34.1%的剂量在前24小时内排出。（这只猴子观察到的粪便放射性活动量较大，可能是由于尿液放射性污染。）很少的剂量转化为了放射性乙醛酸、马尿酸或草酸。

Two female rhesus monkeys were dosed orally with 4 mL/kg of 500 mg/kg homogenous 1-(14)C-glycolic acid, 0.73 uC/mmol, in aq. solution via stomach tube. Urine was collected at intervals of 0-8, 8-24, 24-48, 48-72, and, for one monkey, 72-96 hr. Over a 72 hr period one animal excreted, as a percentage of the dose, 53.2% (14)C, 51.4% of which was excreted in the urine; 51.4% of the dose was excreted in the first 24 hr. The second animal excreted a total of 42.2% (14)C over 96 hr, 36.6% of which was excreted in the urine; 34.1% of the dose was excreted in the first 24 hr. (The greater amount of fecal radioactivity observed for this monkey could have been due to urinary radioactivity contamination.) Very little of the dose was converted to radioactive glyoxylic, hippuric, or oxalic acid.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

10% 甘醇酸水溶液的皮肤渗透性是在体外使用87岁女性腹部皮肤进行确定的。水溶液是通过将0.8 mL 12.473% 甘醇酸溶液与0.2 mL的(2-(14)C)甘醇酸溶液混合制备而成，后者的放射性浓度为44 mCi/mmol 或 250 μCi/mL，含有0.216 mg甘醇酸。含有0.8 mL 12.473% 甘醇酸溶液和0.2 mL水的混合物的pH值为3.72。通过测定氚标记水的渗透系数来评估皮肤完整性。将20 μL的10%甘醇酸水溶液（活性物质2 mg）置于角质层表面；使用了13个重复样本。在应用后1、2、4、6、8和24小时分别取样200 μL，并使用液体闪烁计数器进行计数。在取24小时样本后，皮肤表面用蒸馏水冲洗3次。24小时内的平均总吸收量为2.6 ± 0.37 μg/平方厘米，占施加剂量的0.15 ± 0.02%。在大约3.8小时的滞后时间后，进入稳态扩散阶段，速率为0.13 μg/平方厘米/小时。24小时后，皮肤中回收了48 ± 0.05%的剂量，受体相中发现了0.15 ± 0.02%。总回收率为102.9% ± 2.9%。

Skin penetration of 10% aq. Glycolic acid was determined in vitro using human female (age 87 years) abdominal skin. The aq. solution was prepared by adding 0.8 mL 12.473% glycolic acid solution to 0.2 mL of (2-(14)C) glycolic acid solution, 44 mCi/mmol or 250 iCi/mL that contained 0.216 mg glycolic acid. The pH of a mixture containing 0.8 mL of the 12.473% glycolic acid solution and 0.2 mL of water was 3.72. Skin integrity was assessed by determining the permeability coefficient of tritiated water. Twenty uL of 10% aq. glycolic acid solution, 2 mg active, was placed on the stratum corneum surface; 13 replicates were used. Samples of 200 uL, which were taken 1, 2, 4, 6, 8, and 24 hr after application, were counted using a liquid scintillation counter. The skin surface was rinsed 3 times after the 24 hr sample was taken. The average total absorption over 24 hr 2.6 +/= 0.37 ug/sq cm representing 0.15 +/= 0.02% of the applied dose. A lag time of approximately 3.8 hr was followed by a period of steady-state diffusion at a rate of 0.13 ug/sq cm/hr. After 24 hr, 48 +/= 0.05% of the dose was recovered in the skin and 0.15 +/= 0.02% was found in the receptor phase. Total recovery was 102.9% +/= 2.9%.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  8
• 危险品标志：
  C
• 安全说明：
  S23,S26,S36/37/39,S45
• 危险类别码：
  R22,R34
• WGK Germany：
  1
• 海关编码：
  2918199090
• 危险品运输编号：
  UN 3265 8/PG 3
• 危险类别：
  8
• RTECS号：
  MC5250000
• 包装等级：
  II
• 危险标志：
  GHS05,GHS07
• 危险性描述：
  H314,H332
• 危险性防范说明：
  P261,P280,P303 + P361 + P353,P304 + P340 + P310,P305 + P351 + P338
• 储存条件：
  1. 本品应密封保存于阴凉避光处。 2. 包装方面，建议使用玻璃瓶或内衬的铁桶，若大量运输，则推荐采用带有保温措施及外加热管的槽车。在寒冷天气卸货时，请注意保温。同时，所有包装容器上都应有警告标记，提醒不要让其接触皮肤、眼睛和衣物。

SDS

第一部分：化学品名称

化学品中文名称：	羟基乙酸；乙醇酸
化学品英文名称：	Hydroxyacetic acid；Glycolic acid
中文俗名或商品名：
Synonyms：
CAS No.：	79-14-1
分子式：	C 2 H 4 O 3
分子量：	76.05

第二部分：成分/组成信息

纯化学品 混合物

化学品名称：羟基乙酸；乙醇酸

有害物成分 含量 CAS No.

第三部分：危险性概述

危险性类别：
侵入途径：	吸入 食入
健康危害：	本品对眼睛、皮肤、粘膜和上呼吸道有刺激作用。
环境危害：	对环境有危害，对水体和大气可造成污染。
燃爆危险：	本品可燃，具强腐蚀性、刺激性，可致人体灼伤。

第四部分：急救措施

皮肤接触：	脱去污染的衣着，用流动清水冲洗。若有灼伤，按酸灼伤处理。
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。就医。
食入：	误服者给饮牛奶或蛋清。就医。

第五部分：消防措施

危险特性：	受高热分解，放出刺激性烟气。粉体与空气可形成爆炸性混合物，当达到—定的浓度时，遇火星会发生爆炸。
有害燃烧产物：	一氧化碳、二氧化碳。
灭火方法及灭火剂：	雾状水、泡沫、二氧化碳、干粉、砂土。
消防员的个体防护：	消防人员须戴好防毒面具，在安全距离以外，在上风向灭火。
禁止使用的灭火剂：
闪点(℃)：	无资料
自燃温度(℃)：	引燃温度(℃)：无资料
爆炸下限[%(V/V)]：	无资料
爆炸上限[%(V/V)]：	无资料
最小点火能(mJ)：
爆燃点：
爆速：
最大燃爆压力(MPa)：
建规火险分级：

第六部分：泄漏应急处理

应急处理：

戴好防毒面具和手套。用大量水冲洗，经稀释的洗液放入废水系统。如大量泄漏，收集回收或无害处理后废弃。

第七部分：操作处置与储存

操作注意事项：	密闭操作，局部排风。操作人员必须经过专门培训，严格遵守操作规程。建议操作人员佩戴防尘面具（全面罩），穿连衣式胶布防毒衣，戴橡胶手套。远离火种、热源，工作场所严禁吸烟。使用防爆型的通风系统和设备。避免产生粉尘。避免与氧化剂、还原剂、碱类接触。搬运时要轻装轻卸，防止包装及容器损坏。配备相应品种和数量的消防器材及泄漏应急处理设备。倒空的容器可能残留有害物。
储存注意事项：	储存于阴凉、通风的库房。远离火种、热源。应与氧化剂、还原剂、碱类分开存放，切忌混储。配备相应品种和数量的消防器材。储区应备有合适的材料收容泄漏物。

第八部分：接触控制/个体防护

最高容许浓度：	中 国 MAC：未制订标准前苏联 MAC：未制订标准美国TLV—TWA：未制订标准
监测方法：
工程控制：	密闭操作，局部排风。
呼吸系统防护：	空气中浓度较高时，戴面具式呼吸器。
眼睛防护：	戴化学安全防护眼镜。
身体防护：	穿防酸碱工作服。
手防护：	戴防化学品手套。
其他防护：	工作后，淋浴更衣。定期体检。

第九部分：理化特性

外观与性状：	无色易潮解的晶体，70%的工业品是一种淡黄色液体。
pH：
熔点(℃)：	78-79
沸点(℃)：	100(分解)
相对密度(水=1)：	1．49
相对蒸气密度(空气=1)：
饱和蒸气压(kPa)：
燃烧热(kJ/mol)：
临界温度(℃)：
临界压力(MPa)：
辛醇/水分配系数的对数值：
闪点(℃)：	无资料
引燃温度(℃)：	引燃温度(℃)：无资料
爆炸上限%(V/V)：	无资料
爆炸下限%(V/V)：	无资料
分子式：	C 2 H 4 O 3
分子量：	76.05
蒸发速率：
粘性：
溶解性：	溶于水，溶于甲醇、乙醇、乙酸乙酯，微溶于乙醚，不溶于烃类。
主要用途：	用于羊毛和耐纶的助染剂，也用于电镀、粘合剂和金属洗涤等。

第十部分：稳定性和反应活性

稳定性：	在常温常压下 稳定
禁配物：	碱、氧化剂；还原剂。
避免接触的条件：
聚合危害：	不能出现
分解产物：	一氧化碳、二氧化碳。

第十一部分：毒理学资料

急性毒性：	属低毒类，对皮肤和眼睛有极剧烈的灼伤作用。 LD50：1950mg／kg(大鼠经口)；1920mg／kg(豚鼠经口) LC50：大鼠吸入饱和蒸气6小时无作用。
急性中毒：
慢性中毒：
亚急性和慢性毒性：
刺激性：
致敏性：
致突变性：
致畸性：
致癌性：

第十二部分：生态学资料

生态毒理毒性：
生物降解性：
非生物降解性：
生物富集或生物积累性：

第十三部分：废弃处置

废弃物性质：
废弃处置方法：	处置前应参阅国家和地方有关法规。建议用焚烧法处置。
废弃注意事项：

第十四部分：运输信息

危险货物编号：
UN编号：
包装标志：
包装类别：
包装方法：
运输注意事项：	储存于阴凉、通风仓间内。远离火种、热源。包装要求密封，不可与空气接触。应与氧化剂、酸类、碱类分开存放。搬运时要轻装轻卸，防止包装及容器损坏。起运时包装要完整，装载应稳妥。运输过程中要确保容器不泄漏、不倒塌、不坠落、不损坏。严禁与氧化剂、还原剂、碱类、食用化学品等混装混运。运输途中应防曝晒、雨淋，防高温。运输车船必须彻底清洗、消毒，否则不得装运其它物品。
RETCS号：
IMDG规则页码：

第十五部分：法规信息

国内化学品安全管理法规：	化学危险物品安全管理条例 (1987年2月17日国务院发布)，化学危险物品安全管理条例实施细则 (化劳发[1992] 677号)，工作场所安全使用化学品规定 ([1996]劳部发423号)等法规，针对化学危险品的安全使用、生产、储存、运输、装卸等方面均作了相应规定。
国际化学品安全管理法规：

第十六部分：其他信息

参考文献：	1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
填表时间：	年月日
填表部门：
数据审核单位：
修改说明：
其他信息：	4
MSDS修改日期：	年月日

制备方法与用途

乙醇酸简介

乙醇酸又称羟基乙酸或甘醇酸，不仅是一种重要的有机合成中间体和化工产品，还广泛应用于有机合成、清洗、电镀、纺织、皮革、灭菌等行业。近年来的研究表明，其聚合物具有生物可降解性，能有效解决传统塑料制品难以降解的问题，并在医学、包装等领域有广泛应用。

应用

乙醇酸可用于制备高分子量的聚乙醇酸。虽然传统的高分子材料如PET、PE、PP、PS等为人们的生活带来了诸多便利，在社会经济发展中发挥了重要作用，但由于回收利用不完善且无法自然降解或难以降解，导致了严重的“白色污染”。随着环保意识的提升，各国相继出台限塑政策，发展可降解、环境友好的高分子材料替代传统不可降解材料已成为研究的重点方向。

皮肤保湿

乙醇酸通过干扰细胞表面结合力降低角质形成细胞的黏连性，加速表皮细胞的脱落与更新，并刺激真皮胶原合成以增强保湿功能。此外，其羟基较强的吸水能力及渗入真皮后促进天然保湿因子生成的特点，使其具备良好的保湿效果。

用途

乙醇酸是重要的化工原料，可用于制造乙二醇、乙醇酸薄荷酯及乙醇酸奎宁酯等产品。还可制取鞣革剂、染发剂、皮革染色剂、纤维染色剂、胶粘剂、金属螯合剂、石油破乳剂、电镀药剂、铝板蚀刻剂、纤维素织物的交联剂、不锈钢电抛光剂，以及食品加工厂及牛棚的清洁剂、消毒剂和锅炉防垢剂等。

制备

一种由乙醇酸甲酯生产乙醇酸的方法包括以下步骤：

1. 将乙醇酸甲酯与水按摩尔比1:5～30的比例加入精馏塔，利用树脂类固体酸催化剂，在真空度为10～101kPaA和80～85℃的条件下进行反应精馏。保持釜液温沸腾温度不变，持续回收塔顶甲醇冷凝液全回流10～30min后，调节回流比至0.5～3，反应2～6h，最终采出乙醇酸水溶液。
2. 蒸发浓缩步骤1得到的乙醇酸水溶液，将其中乙醇酸的质量含量提浓至70～90wt％。
3. 进行脱色处理直至无色。
4. 结晶析出晶状乙醇酸，过滤分离并淋洗，最后进行真空干燥以获得成品乙醇酸晶体。
5. 将步骤4中滤液直接浓缩或与步骤1得到的乙醇酸水溶液混合后浓缩，循环利用。

化学性质

纯品为无色易潮解的晶体，工业品则为70%水溶液的淡黄色液体，具有类似烧焦糖的气味。它溶于水、乙醇及乙醚。

用途

• 制革助剂：用于皮革处理。
• 水消毒剂和牛奶棚消毒剂。
• 有机合成原料：主要用于生产乙二醇。
• 清洗剂：2%的羟基乙酸与1%甲酸混合配制成洗涤剂，适合清洗空调机；可制取纤维染色剂、清净剂、焊接剂配料等。
• 电镀液添加剂：如钠盐和钾盐用作电镀液辅助成分。

其他用途

• 用于有机合成与日化品替代果酸。
• 作为羊毛及腈纶的助染剂，也可制作乙二醇、薄荷酯类和奎宁酯等产品的原料以及酒石酸的代用品。
• 用作分析试剂，调节pH值并参与有机合成中的反应如薄荷脑和奎宁酯类制备、染发剂配制。

生产方法

1. 氯乙酸法：在碱性条件下水解粗品，经甲醇酯化得羟基乙酸甲酯后蒸馏再水解。
2. 高温高压法：通过甲醛、二氧化碳和水反应获得。
3. 氰化水解法：由甲醛与氢氰酸为原料合成后再进行酸性水解得到成品。
4. 氰化钠法：以甲醛和氰化钠为原料，经过两步制备完成。

反应信息

• 作为反应物：
  描述：

  羟基乙酸 在 盐酸 作用下， 以7%的产率得到氯乙酸
  参考文献：
  名称：

  Monochloroacetic acid from hydroxyacetic acid

  摘要：

  从羟基乙酸生产单氯乙酸的方法包括向反应区域供应羟基乙酸和水氯化氢，并在存在碘化氢催化剂的情况下将羟基乙酸与水氯化氢接触，在温度在100度至250度C之间，并在足以保持水氯化氢处于液相的压力下进行。最好在约130度至200度C的温度下进行反应。

  公开号：

  US04221921A1
• 作为产物：
  描述：

  1,4-二氧杂环-2,5-己二酮 在 水 作用下， 生成 羟基乙酸
  参考文献：
  名称：

  Bischoff; Walden, Chemische Berichte, 1893, vol. 26, p. 264

  摘要：

  DOI：
• 作为试剂：
  描述：

  甲酸铵 、 1,2-二硝基苯 在 羟基乙酸 作用下， 以85%的产率得到苯并咪唑
  参考文献：
  名称：

  One-pot photocalalytic reductive formylation of nitroarenes via multielectron transfer by carbon nitride in functional eutectic medium

  摘要：

  In the past years organic semiconductor photocatalysis has made the remarkable advances in developing efficient synthetic chemical routes to well refined structures. Until now, most efforts were focused on optimizing of the semiconductor photocatalyst, while solvents were largely ignored. Herein, we design a series of functional deep eutectic solvents (DES) with adjustable physicochemical properties - density, viscosity, glass transition temperature, and chemical activity towards reductive formylation of nitroarenes. The DES are prepared from abundant, sustainable resources, which makes them an affordable alternative to the ionic liquids, even on larger industrial scales. By combining the ammonium formate-based DES with carbon nitride photocatalyst, we enable the simultaneous six-electron reduction of nitrocompounds to the corresponding N-substituted formamides and benzimidazoles in one pot. (C) 2019 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jcat.2019.10.010

文献信息

• [EN] FUSED PYRAZOLE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLE CONDENSÉS UTILISÉS EN TANT QU'INHIBITEURS DE JAK
  申请人：ALMIRALL SA

  公开号：WO2017220431A1

  公开（公告）日：2017-12-28

  Novel fused pyrazole derivatives of Formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  公开了式（I）的新型融合吡唑衍生物；以及它们的制备方法，包含它们的药物组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。
• Synthesis of New Phospholipids Linked to Steroid-Hormone Derivatives Designed for Two-Dimensional Crystallization of Proteins
  作者：Luc Lebeau、Pierre Oudet、Charles Mioskowski

  DOI：10.1002/hlca.19910740810

  日期：1991.12.11

  The synthesis of phospholipids 1n–3n, rationally designed for two-dimensional crystallization of progesterone and estradiol receptors, is reported. The structure of these lipids provides them with essential properties such as fluidity and stability when spread into monolayers at the air/H2O interface, affinity for the protein to be crystallized, and accessibility of the ligand under the lipid monolayer

  据报道，合理设计用于孕酮和雌二醇受体的二维结晶的磷脂1 n - 3 n的合成。这些脂质的结构为它们提供了必要的特性，例如当在空气/ H 2 O界面扩散为单层时的流动性和稳定性，对要结晶的蛋白质的亲和力以及脂质单层下配体的可及性。
• [EN] TRIPARTITE MODULATORS OF ENDOSOMAL G PROTEIN-COUPLED RECEPTORS<br/>[FR] MODULATEURS TRIPARTITES DE RÉCEPTEURS COUPLÉS AUX PROTÉINES G DES ENDOSOMES
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017112792A1

  公开（公告）日：2017-06-29

  The present invention relates to tripartite compounds comprising a modulator moiety for endosomal G protein-coupled receptors like neurokinin-1 receptor, a linker and a lipid anchor suitable for anchoring the tripartite compound into a plasma membrane. The present invention also relates to a prodrug and a pharmaceutical composition comprising the tripartite compound and the use of the tripartite compound for the treatment of a disease or disorder mediated by endosomal G protein-coupled receptors signalling like NK1R signalling.

  本发明涉及三部分化合物，包括用于内体高尔基蛋白偶联受体（如神经激肽-1受体）的调节子基团，一个连接物和一个适合将三部分化合物锚定到细胞膜的脂质锚。本发明还涉及一种前药和含有三部分化合物的药物组合物，以及利用三部分化合物治疗由内体高尔基蛋白偶联受体信号传导介导的疾病或紊乱的用途。
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018137593A1

  公开（公告）日：2018-08-02

  Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

  提供了抑制LRRK2激酶活性的新化合物，以及它们的制备方法、含有它们的组合物以及它们在治疗或预防与LRRK2激酶活性相关或以其为特征的疾病中的用途，例如帕金森病、阿尔茨海默病和肌萎缩侧索硬化症（ALS）。
• Cobalt(II) complexes based on (1-methyl-1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl) methanol derivative: synthesis, crystal structure, spectroscopy, DFT calculations, and antioxidant activity
  作者：Anfel Benhassine、Houssem Boulebd、Barkahem Anak、Abdelmalek Bouraiou、Sofiane Bouacida、Mustapha Bencharif、Ali Belfaitah

  DOI：10.1080/00958972.2018.1428742

  日期：2018.1.17

  computational study of two new cobalt(II) complexes as [Co(Hmbm)2(OAc)2] and [Co(Hmbm)2(H2O)2]Cl2 (Hmbm = (1-methyl-1H-benzo[d]imidazol-2-yl)methanol). Both complexes were characterized by FT-IR and UV–vis spectroscopy, elemental analysis, and single-crystal X-ray crystallography. The molecular geometries, electronic transitions, and vibrational frequencies of the two complexes and the ligand (Hmbm) in the

  摘要 在本文中，我们对两种新的钴 (II) 配合物 [Co(Hmbm)2(OAc)2] 和 [Co(Hmbm)2(H2O)2]Cl2 (Hmbm = ( 1-甲基-1H-苯并[d]咪唑-2-基)甲醇)。两种配合物均通过 FT-IR 和 UV-vis 光谱、元素分析和单晶 X 射线晶体学表征。使用全局杂化 (B3LYP) 和范围分离杂化 (CAM-B3LYP) 密度泛函计算了两种配合物和基态配体 (Hmbm) 的分子几何结构、电子跃迁和振动频率。电子跃迁态的激发态和电荷转移特性的定性描述是通过绘制主要态的自然跃迁轨道 (NTO) 进行的，并将其分配给 LMCT。

表征谱图