1,1,1,2-四氟乙烷 | 811-97-2

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 中文名称: 1,1,1,2-四氟乙烷
• 中文别名: 诺氟烷；四氟乙烷；1，1，1，2-四氟乙烷；R134A制冷剂；R134a
• 英文名称: 1,1,1,2-tetrafluoroethane
• 英文别名: HFA-134a
• CAS: 811-97-2
• 化学式: C₂H₂F₄
• mdl: MFCD00066608
• 分子量: 102.031
• InChiKey: LVGUZGTVOIAKKC-UHFFFAOYSA-N

物化性质

• 熔点：
  -101 °C
• 沸点：
  -26 °C
• 密度：
  1.223±0.06 g/cm3(Predicted)
• 物理描述：
  1,1,1,2-tetrafluoroethane appears as a colorless gas with a slight ethereal odor. Vapors are heavier than air. Shipped liquefied under own vapor pressure. Flash point 351°F. Inhalation at high concentrations is harmful and may cause heart irregularities, unconsciousness or death without warning. Liquid contact may cause frostbite. Vapors can replace the available oxygen.
• 颜色/状态：
  Colorless gas
• 气味：
  Faint ethereal odor
• 溶解度：
  In water, 2.04X10+3 mg/L at 25 °C (est)
• 蒸汽密度：
  Relative vapor density (air = 1): 3.5
• 蒸汽压力：
  4990 mm Hg at 25 °C
• 亨利常数：
  0.05 atm-m3/mole
• 大气OH速率常数：
  4.90e-15 cm3/molecule*sec
• 稳定性/保质期：

  化学稳定性：一般情况下稳定。

  危险反应的可能性：未报道特殊反应性。

  应避免接触热源，并防止与氧化剂、碱金属和碱土金属接触。

  可能产生的危险分解产物包括一氧化碳、二氧化碳和氟化氢。

• 分解：
  When heated to decomposition it emits toxic vapors of /flouride/.
• 粘度：
  0.204 cP at 25 °C
• 汽化热：
  47.52 cal/g at 0 °C
• 表面张力：
  8.366 dyns/cm at 25 °C
• 保留指数：
  219;219

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

[U-(14)C]-1,1,1,2-四氟乙烷([U-(14)C]-HFC134a)在雄性和雌性大鼠体内的代谢命运和处置已通过吸入10,000 ppm浓度的气体单次暴露1小时后确定。吸入剂量中，大约1%在暴露后通过尿液、粪便和呼出气体中被回收，表明这种氟碳化合物通过肺部的吸收较差。在这1%中，大约有三分之二在暴露停止后的1小时内以未改变的HFC134a形式呼出。剩余的放射性物质以[(14)C]-二氧化碳的形式呼出，或者以三氟乙酸的形式通过尿液和粪便排出。二氧化碳是HFC134a的主要代谢物，在雄性和雌性大鼠中分别占吸入剂量的0.22%和0.27%。尿液排泄占总剂量的0.09%，粪便排泄占0.04%，两种性别都如此。总代谢量，即尿液、粪便中的放射性活性和二氧化碳的总和，在雄性和雌性大鼠中分别占吸入剂量的0.34%和0.40%。在放射性标记物的排泄速率、途径或数量上，性别之间没有显著差异。在暴露后5天对一系列组织进行分析，显示出放射性活性的相对均匀分布。没有证据表明HFC134a或其代谢物被任何分析的组织或器官特异性摄取，包括脂肪。

The metabolic fate and disposition of [U-(14)C]-1,1,1,2-tetrafluoroethane ([U-(14)C]-HFC134a) has been determined in the male and female rat following a 1 hr single exposure by inhalation to atmospheres of 10,000 ppm. Of the inhaled dose, approx. 1% was recovered in urine, feces and expired air postexposure indicating that absorption of this fluorocarbon across the lung is poor. Of this 1%, approx, two-thirds were exhaled within 1 hr of the cessation of exposure as unchanged HFC134a. The remaining radioactivity was exhaled as [(14)C]-carbon dioxide or excreted in urine and feces as trifluoroacetic acid. Carbon dioxide was the major metabolite of HFC134a accounting for 0.22 and 0.27% of the inhaled dose in the male and female rat, respectively. Urinary excretion accounted for 0.09% of the dose and fecal excretion 0.04% of the dose by both sexes. Total metabolism measured as the sum of the radioactivities in urine, feces and as carbon dioxide amounted to 0.34 and 0.40% of the inhaled dose in male and female, respectively. There were no major sex differences in the rates, routes or amounts of radiolabel excreted. Analysis of a range of tissues at 5 days postexposure showed a relatively uniform distribution of radioactivity. There was no evidence for a specific uptake of HFC134a or a metabolite into any organ or tissue analyzed, including fat.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氟氯烃替代品1,1,1,2-四氟乙烷会受到大鼠、兔子和人类肝脏微粒体中细胞色素p450的代谢。在大鼠和兔中，p450形式2E1是1,1,1,2-四氟乙烷生物转化的主要低KM、高速率催化剂，并且在比1,1,1,2-四氟乙烷毒性更大的其他四卤代烷（例如，1,2-二氯-1,1-二氟乙烷）的代谢中起着突出作用。在这项研究中，确定人类p450 2E1的同源基因在1,1,1,2-四氟乙烷的代谢中扮演着类似重要的角色。在来自12个人的肝微粒体中，来自p450 2E1水平相对较高的个体的制剂代谢1,1,1,2-四氟乙烷的速率比这种酶水平较低的个体的微粒体高5到10倍；1,1,1,2-四氟乙烷代谢速率的增加与p450 2E1表达的增加有特定联系。得出这一结论的主要证据来自使用二乙基二硫代氨基甲酸酯基于机制的p450 2E1失活研究、p-硝基酚（p450 2E1的高亲和力底物）对1,1,1,2-四氟乙烷氧化的竞争性抑制、研究人群中1,1,1,2-四氟乙烷脱氟速率与p-硝基酚羟基化速率之间的强正相关，以及p450 2E1水平与卤代烃氧化速率的相关性。因此，我们的发现支持人类代谢1,1,1,2-四氟乙烷在性质上与用于这种卤代烃毒理学评估的物种（大鼠和兔）相似。尽管基于实验室动物毒理学评估，大多数人类不太可能因1,1,1,2-四氟乙烷暴露而面临危险，但我们的结果建议对于有化学暴露史与p450 2E1升高相当的个体（即，频繁接触乙醇、三氯乙烯或吡啶等物质），应尽量减少1,1,1,2-四氟乙烷的暴露。此外，这些发现表明，目前作为氟氯烃替代品正在考虑的某些其他卤代乙烷的毒性评估应在p450 2E1升高的动物中进行考虑。

The chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane is subject to metabolism by cytochrome p450 in hepatic microsomes from rat, rabbit, and human. In rat and rabbit, the p450 form 2E1 is a predominant low KM, high rate catalyst of 1,1,1,2-tetrafluoroethane biotranformation and is prominently involved in the metabolism of other tetrahaloalkanes of greater toxicity than 1,1,1,2-tetrafluoroethane (eg, 1,2-dichloro-1,1-difluoroethane). In this study, it was determined that the human ortholog of p450 2E1 plays a role of similar importance in the metabolism of 1,1,1,2-tetrafluoroethane. In human hepatic microsomes from 12 individuals, preparations from subjects with relatively high p450 2E1 levels were shown to metabolize 1,1,1,2-tetrafluoroethane at rates 5- to 10-fold greater than microsomes of individuals with lower levels of this enzyme; the increased rate of metabolism of 1,1,1,2-tetrafluoroethane was specifically linked to increased expression of p450 2E1. The primary evidence for the conclusion is drawn from studies using mechanism based inactivation of p450 2E1 by diethyldithiocarbamate, competitive inhibition of 1,1,1,2-tetrafluoroethane oxidation by p-nitrophenol (a high affinity substrate for p450 2E1), strong positive correlations of rates of 1,1,1,2-tetrafluoroethane defluorination with p-nitrophenol hydroxylation in the study population, and correlation of p450 2E1 levels with rates of halocarbon oxidation. Thus, our findings support the conclusion that human metabolism of 1,1,1,2-tetrafluoroethane is qualitatively similar to that of the species (rat and rabbit) used for toxicological assessment of this halocarbon. Although hazard from 1,1,1,2-tetrafluoroethane exposure is not anticipated in most humans (based on toxicological evaluation in laboratory animals), our results suggest that 1,1,1,2-tetrafluoroethane exposure should be minimized for individuals with chemical exposure histories commensurate with elevation of p450 2E1 (ie, frequent contact with agents such as ethanol, trichloroethylene, or pyridine). Furthermore, these findings suggest that toxicity assessment of certain other haloethanes currently under consideration as replacements for chlorofluorocarbons should be considered in animals with elevated p450 2E1.

来源:Hazardous Substances Data Bank (HSDB)

代谢

1,1,1,2-四氟乙烷，由于不具有消耗臭氧的潜力，已被选作空调和冷水机组中二氯二氟甲烷的替代制冷剂，以及药用气雾剂的推进剂。使用大鼠和家兔的各种范式研究表明，1,1,1,2-四氟乙烷的毒性潜力非常小。为了加强预测与1,1,1,2-四氟乙烷暴露相关的人类危害，评估了人类肝微粒体对这种卤代烃的代谢速率，相对于来自大鼠和家兔的类似组织制备物。人类微粒体通过一种常见的细胞色素p450催化反应去除了1,1,1,2-四氟乙烷中的氟。从绝对值来看，人类微粒体对1,1,1,2-四氟乙烷的代谢速率非常低，在评估的样本中个体间变化很小（1.3 ± 0.3 nmol氟离子/mg蛋白质/15分钟，x ± 标准差，n = 10），并且没有超过大鼠或家兔肝微粒体的代谢速率。这些发现支持了这样的论点，即为了表征1,1,1,2-四氟乙烷的毒性，特别是可能由卤代烃代谢产物介导的毒性，实验室动物是人类的一个足够好的替代物。

1,1,1,2-Tetrafluoroethane, which lacks ozone depleting potential, has been selected as a replacement refrigerant for dichlorodifluoromethane in air conditioning and chiller applications, and as a propellant for pharmaceutical aerosols. A variety of paradigms using rats and rabbits have shown that 1,1,1,2-tetrafluoroethane has very little toxic potential. To strengthen the prediction of human hazard associated with 1,1,1,2-tetrafluoroethane exposure, the rate of metabolism of this halocarbon by human hepatic microsomes was evaluated relative to similar tissue preparations derived from rats and rabbits. Human microsomes defluorinated 1,1,1,2-tetrafluoroethane in a cytochrome p450 catalyzed reaction, common also to rat and rabbit. In absolute terms, the maximal rate of 1,1,1,2-tetrafluoroethane metabolism by human microsomes was very low, showed little interindividual variation among the samples evaluated (1.3 : 0.3 nmol fluoride ions/mg protein/15 min, x : standard deviation, n = 10), and did not exceed that in rat or rabbit liver microsomes. These findings support the argument that for characterization of 1,1,1,2-tetrafluoroethane toxicity, especially that which may be mediated by products of halocarbon metabolism, laboratory animals are an adequate surrogate for humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

1,1,1,2-四氟乙烷（R-134a），一种非耗臭氧的空调制冷剂和药物制剂的推进剂，在大鼠肝微粒体中被氧化脱氟。在本报告中，我们展示了通过吡啶给药在大鼠中诱导细胞色素P-450IIE1，导致肝微粒体对R-134a的代谢速率增加了8倍（Vmax 47 vs. 6 nmol F-/mg微粒体蛋白/15分钟）。此外，当数据根据P-450含量进行标准化时，IIE1富集的微粒体制备物中对R-134a的代谢增加了4倍。相比之下，苯巴比妥和阿罗氯1254降低了肝微粒体对此功能的特定活性。通过西方印迹评估，只有来自吡啶处理大鼠的微粒体中P-450IIE1的含量显著升高。对硝基酚和苯胺，这两种在大鼠P-450IIE1下以高速率代谢的物质，降低了肝微粒体对R-134a脱氟的速率；Dixon图分析表明竞争性抑制，Ki值为36微M对硝基酚或115微M苯胺。吡啶也显著诱导了兔肝微粒体催化的R-134a脱氟。从兔肝纯化的单个P-450同工酶的研究显示，苯巴比妥和多环芳烃诱导的同工酶（IIB1和IA2）对R-134a的脱氟速率可以忽略不计（分别为1.9和0.4 nmol F-/nmol P-450/60分钟）。相比之下，P-450IIE1以相对较高的速率催化R-134a的脱氟（16.2 nmol F-/nmol P-450/60分钟）；IA1同工酶，它也可以被像吡啶这样的含氮杂环诱导，也具有一定的活性（5.3 nmol F-/nmol P-450/60分钟）。

1,1,1,2-Tetrafluoroethane (R-134a), a nonozone-depleting alternative air-conditioning refrigerant and propellant for pharmaceutical preparations, is oxidatively defluorinated by rat hepatic microsomes. In this report we show that induction of cytochrome P-450IIE1 in rats, by pyridine administration, resulted in an 8-fold increase in the rate of R-134a metabolism by hepatic microsomes (Vmax 47 vs. 6 nmol F-/mg microsomal protein/15 min). Furthermore, when data were normalized for P-450 content, a 4-fold increase in R-134a metabolism was noted for IIE1-enriched microsome preparations. In contrast, phenobarbital and Aroclor 1254 decreased the specific activity of hepatic microsomes for this function. The microsomal content of P-450IIE1, as evaluated by Western blot, was elevated significantly only in microsomes from pyridine-treated rats. p-Nitrophenol and aniline, which are metabolized at high rates by rat P-450IIE1, decreased the rate of R-134a defluorination by hepatic microsomes; Dixon plot analysis indicated competitive inhibition with a Ki of 36 microM p-nitrophenol or 115 microM aniline. Pyridine also potently induced defluorination of R-134a catalyzed by rabbit liver microsomes. Studies with individual P-450 isozymes purified from rabbit liver showed that the phenobarbital- and polycyclic hydrocarbon-induced isozymes (IIB1 and IA2) defluorinated R-134a at negligible rates (1.9 and 0.4 nmol F-/nmol P-450/60 min, respectively). In contrast, P-450IIE1 catalyzed defluorination of R-134a at a relatively high rate (16.2 nmol F-/nmol P-450/60 min); isozyme IA1, which also is induced by nitrogen-containing heterocycles such as pyridine, was somewhat active (5.3 nmol F-/nmol P-450/60 min).

来源:Hazardous Substances Data Bank (HSDB)

代谢

1,1,1,2-四氟乙烷的肝细胞代谢进行了研究。从雄性Fischer 344大鼠中分离出肝细胞，并暴露于含有1,1,1,2-四氟乙烷和/或卤烷的气氛中，并分析其氟化物含量。在肝细胞暴露于25%的1,1,1,2-四氟乙烷后，检测到了氟化物，其数量随着细胞数量的增加和1,1,1,2-四氟乙烷浓度的增加而增加。1,1,1,2-四氟乙烷浓度与氟化物之间存在非线性关系，表明可能存在底物饱和。当肝细胞在25%的1,1,1,2-四氟乙烷和卤烷的条件下培养时，卤烷的浓度与氟化物产量的减少有关。用苯巴比妥处理的动物肝细胞在12.5%或更低的1,1,1,2-四氟乙烷存在时，产生的氟化物与未处理的动物相当，然而在25%或更高浓度的1,1,1,2-四氟乙烷中，用苯巴比妥处理的细胞比未处理的细胞产生更多的氟化物。得出结论，1,1,1,2-四氟乙烷可以被肝细胞代谢，并且可能涉及细胞色素p450。

The metabolism of 1,1,1,2-tetrafluoroethane by hepatocytes was investigated. Liver cells were isolated from male Fischer 344 rats and exposed to atmospheres containing 1,1,1,2-tetrafluoroethane and/or halothane and analyzed for fluoride. Fluoride was detected after exposure of hepatocytes to 25% 1,1,1,2-tetrafluoroethane, and the amount increased with the number of cells and with increasing 1,1,1,2-tetrafluoroethane concn. A nonlinear relationship was seen between 1,1,1,2-tetrafluoroethane concn and fluoride, indicating probable substrate saturation. When hepatocytes were incubated with 25% 1,1,1,2-tetrafluoroethane and halothane, there was a reduction in fluoride production that was related to the concn of halothane. Hepatocytes from phenobarbital treated animals produced as much fluoride as untreated animals in the presence of 12.5% or less 1,1,1,2-tetrafluoroethane, however at a concn of 25% or more 1,1,1,2-tetrafluoroethane, phenobarbital treated cells produced more fluoride than untreated cells. It was concluded that 1,1,1,2-tetrafluoroethane can be metabolized by liver cells, and may involve cytochrome p450.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：1,1,1,2-四氟乙烷（HFC-134a）是一种无色气体，带有淡淡的气味。它目前在美国没有注册为农药使用，但批准的农药用途可能会定期更改，因此必须咨询联邦、州和地方当局以获取当前批准的用途。它被用作制冷剂、药品的推进剂、泡沫的发泡剂。人类暴露和毒性：健康志愿者暴露于高达8000 ppm HFC-134a的暴露水平并没有对脉搏、血压、心电图或肺功能产生任何不利影响。有报道称HFC-134a引起了外源性过敏性肺泡炎伴嗜酸性粒细胞浸润。在其他案例中，故意吸入含有HFC-134a的商业空气除尘剂导致了严重的口腔和数字冻伤。动物研究：HFC-134a可以在80,000 ppm（8% v/v）及更高水平下诱导狗在对外源性肾上腺素挑战后的心脏敏感化。在大鼠中，连续暴露于50,000 ppm HFC-134a 13、52和104周没有对临床状况、生长和存活产生影响，也没有对各种血液学、临床化学和尿液参数产生影响。HFC-134a处理对小鼠或大鼠暴露于HFC-134a的肿瘤类型、发生率、部位或严重程度没有影响。在暴露于40,000 ppm（166,800 mg/cu m）HFC-134a的家兔中观察到母体体重增加减少，在暴露于50,000 ppm（208,500 mg/cu m）HFC-134a的母鼠中观察到胎儿发育迟缓的迹象。HFC-134a在Ames试验、细胞遗传学和体内微核试验中没有活性，但它确实诱导了非计划性DNA合成。生态毒性研究：这种化合物对少数水生生物的低毒性以及高挥发性表明对水生生物的风险可以忽略不计。

IDENTIFICATION AND USE: 1,1,1,2-Tetrafluoroethane (HFC-134a) is a colorless gas with a faint odor. It is not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. It is used as refrigerant, propellant for pharmaceuticals, blowing agent for foams. HUMAN EXPOSURE AND TOXICITY: Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC-134a did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function. There is a report of extrinsic allergic alveolitis with eosinophil infiltration, caused by HFC-134a. In other case, intentional inhalation of a commercial air-dusting agent containing HFC-134a led to severe orofacial and digital frostbite. ANIMAL STUDIES: HFC- 134a can induce cardiac sensitization in dogs at levels of 80,000 ppm (8% v/v) and higher following exogenous epinephrine challenge. In the rat repeated exposure to 50,000 ppm HFC- 134a for 13, 52, and 104 weeks elicited no effect on clinical condition, growth, and survival, or on a variety of hematological, clinical chemistry, and urinary parameters. There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats exposed to HFC-134a. A reduction in maternal weight gain in rabbits exposed to 40,000 ppm (166,800 mg/cu m) HFC-134a and signs of delayed fetal development in rats following exposure of the dams to 50,000 ppm (208,500 mg/cu m) was noted. HFC-134a was not active in the Ames test, cytogenetics and in vivo micronucleus assays, but it did induce unscheduled DNA synthesis. ECOTOXICITY STUDIES: The low toxicity of this compound to the few aquatic organisms tested as well as high volatility indicate negligible risk to aquatic organisms.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

这种物质可以通过吸入被身体吸收。

The substance can be absorbed into the body by inhalation.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 吸入症状

晕眩。嗜睡。乏力。

Dizziness. Drowsiness. Lethargy.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 皮肤症状

接触液体时：冻伤。

ON CONTACT WITH LIQUID: FROSTBITE.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 副作用

神经毒素 - 急性溶剂综合症

Neurotoxin - Acute solvent syndrome

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

HFC 134a和HFC 227的安全性和药代动力学在两项单独的双盲研究中进行了评估。每种HFC（氢氟烃）都以蒸汽形式通过全身暴露给八名（四名男性和四名女性）健康志愿者。志愿者每周一次接受1小时的暴露，首先暴露于空气，然后暴露于递增浓度的HFC（1000、2000、4000和8000 ppm），中间穿插第二次空气暴露和两次CFC 12（二氯二氟甲烷）暴露（1000和4000 ppm）。将HFC 134a或HFC 227与CFC 12或空气进行比较，没有发现任何临床显著的结果。没有显著的的不良事件，没有证据表明对中枢神经系统有影响，也没有上呼吸道刺激的症状。HFC 134a、HFC 227和CFC 12的血药浓度迅速增加，并与暴露浓度相关，尽管不是严格成比例，并接近稳态。最大血药浓度（C(max)）在男性中往往高于女性。在HFC 134a研究中，C(max)的性别差异仅在CFC 12 4000 ppm和HFC 134a 8000 ppm时具有统计学意义（P < 0.05）。暴露结束后，血药浓度迅速下降，主要是双相的，与暴露浓度无关。对于HFC 134a研究，CFC 12和HFC 134a的t(1/2)alpha（α消除半衰期）都很短（<11分钟）。在所有暴露浓度下，CFC 12和HFC 134a的t(1/2)beta（β消除半衰期）平均值分别为36和42分钟。CFC 12和HFC 134a的平均滞留时间（MRT）分别为42和44分钟。将健康志愿者暴露于高达8000 ppm HFC 134a、8000 ppm HFC 227和4000 ppm CFC 12的暴露水平，并未对脉搏、血压、心电图或肺功能产生任何不利影响。

The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 hr, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females. ... In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t(1/2)beta (beta elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. ... Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

六只雄性和六只雌性Sprague-Dawley大鼠在磁共振成像光谱仪中，仅头部通气1小时，使用含有15%的1,1,1,2-四氟乙烷（HFA-134a）的空气气氛。来自这些动态19F NMR研究的结果表明，在大约暴露25分钟时接近HFA-134a的稳态体内浓度。使用外部标准进行定量积分分析估计这个平台为每只大鼠吸收的HFA-134a为58.3 +/- 11.9毫克。移除测试气氛后，HFA-134a的19F NMR信号迅速消失，雄性大鼠的消除半衰期为4.6 +/- 0.6分钟，雌性大鼠的消除半衰期为4.9 +/- 1.5分钟。数据显示，在吸收量或消除半衰期方面，性别之间没有统计学差异。

Six male and six female Sprague-Dawley rats were ventilated head-only for 1 hr on a 15% atmosphere of 1,1,1,2-tetrafluoroethane (HFA-134a) in air in a magnetic resonance imaging spectrometer. Results from these dynamic 19F NMR studies suggest that a steady-state in vivo concentration of HFA-134a was approached at approximately 25 min into the exposure. Quantitative integration analysis using an external standard estimated this plateau to be 58.3 +/- 11.9 mg of absorbed HFA-134a per rat. The HFA-134a 19F NMR signal disappeared rapidly following removal of the test atmosphere, with an elimination half-life of 4.6 +/- 0.6 min in the male rats and 4.9 +/- 1.5 min in the female rats. The data suggest that there was no statistical difference between the sexes in amount absorbed or in elimination half-lives.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

HFA134a（1,1,1,2-四氟乙烷）是一种非消耗臭氧的候选物质，用于替代计量吸入器（MDIs）中作为推进剂的氯氟烃。计量吸入器广泛用于治疗呼吸道疾病。为确保这种化合物对人体使用的安全性，有必要确定人体内及其选定区域内没有过度或意外的积累。通过使用18F标记的HFA134a的灵敏全身伽马计数技术来测量单次吸入给药后HFA134a在人体全身和区域的吸收、分布和保留情况。在七名健康受试者中，标记的HFA134a在最初的几分钟内通过通气迅速排出，平均有9.6%的放射性物质在5分钟时保留在体内。这种放射性物质的清除呈现出一个明显的终末半衰期，为1.5-4.2小时，平均在5.8小时时，保留在体内的给药剂量小于1%（小于750微克，大约0.2微居里）。放射性的处置与标记的位置无关。因此，没有证据表明有任何显著降解代谢。平均而言，在最初的2小时内，只有0.0056%的给药剂量出现在尿液中。后来的样本中不含有显著的放射性物质。吸入的HFA134a首先分布到全身所有区域，然后在没有明显积累在任何特定区域的情况下清除。

HFA134a (1,1,1,2-tetrafluoroethane) is a nonozone-depleting candidate to replace the chlorofluorocarbons used as propellants in metered-dose inhalers (MDIs) for pharmaceuticals that are widely used in the treatment of respiratory tract disease. As a means for ensuring the safety of such a compound for human use, it is necessary to establish that there is no excessive or unexpected accumulation in the body and in selected regions. A sensitive whole-body gamma-counting technique has been used with 18F-labeled HFA134a to measure the whole-body and regional absorption, distribution, and retention of HFA134a after administration in humans by single-breath inhalation. In seven healthy subjects, labeled HFA134a was rapidly eliminated by ventilation during the first few minutes, with an average of 9.6% of the radioactivity retained in the body at 5 min. This radioactivity cleared with an apparent terminal half-life of 1.5-4.2 hr to leave, on average, < 1% of the administered dose (< 750 micrograms, approximately 0.2 microCi) retained in the body at 5.8 hr. Disposition of radioactivity was independent of the position of label. Thus, there was no evidence of any significant degradative metabolism. On average, only 0.0056% of the administered dose appeared in the urine within the first 2 hr. Later samples contained no significant radioactivity. Inhaled HFA134a first distributed to all regions of the body and then cleared without evident accumulation in any specific region.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

无氯推进剂HFA134a在健康受试者单次和重复给药后的安全性、耐受性和药代动力学进行了评估。使用标记的HFA134a在健康受试者和严重慢性阻塞性肺病（COPD）患者中研究了吸收和处置。生命体征、心电图、肺功能测试和实验室参数测量均未出现临床显著变化。没有报告严重的不良事件。在受试者和患者中，HFA134a主要通过在给药后最初的几分钟内呼出而消除，并在全身分布，没有在任何特定区域明显积累。HFA134a在吸入后迅速吸收，与剂量相关的血药浓度在给药后迅速下降（t1/2 = 31分钟）。代谢不是HFA134a消除的重要途径。还进行了用HFA134a重新配方的沙美特罗和沙丁胺醇MDIs的研究。结果显示，这些MDIs在健康受试者中是安全的，耐受性良好，并且与当前的MDIs给出了类似的药效动力学响应。

The safety, tolerability and pharmacokinetics of the chlorine-free propellant HFA134a were assessed in healthy subjects after single and repeat doses. Absorption and disposition were investigated in healthy subjects and severe chronic obstructive pulmonary disease (COPD) patients using labelled HFA134a. There were no clinically significant changes in vital signs, ECG, pulmonary function tests and laboratory parameters measured. No serious adverse events were reported. In both subjects and patients HFA134a was mainly eliminated by exhalation within the first few minutes after administration and was distributed throughout the body with no obvious accumulation in any specific region. HFA134a was rapidly absorbed after inhalation with dose-related blood concentrations which declined rapidly after dosing (t1/2 = 31 min). Metabolism was not a significant route of elimination of HFA134a. Studies were also performed with salmeterol and salbutamol MDIs reformulated with HFA134a. The results showed that these MDIs were safe and well tolerated in healthy subjects and gave a similar pharmacodynamic response to the current MDIs.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  2.2
• 危险品标志：
  Xi
• 安全说明：
  S23,S38
• WGK Germany：
  1
• 海关编码：
  29033990
• 危险品运输编号：
  UN 3159 2.2
• RTECS号：
  KI8842500
• 危险类别：
  2.2
• 危险标志：
  GHS04
• 危险性描述：
  H280
• 危险性防范说明：
  P410 + P403
• 储存条件：
  技术措施： - 在通风良好的地方进行处理。 - 保持高压状态，确保反应设备内的压力不超过气瓶的压力。 - 安装止回阀在气体感应流路上，并且在内容物用完之前不要拆除该阀门。 - 处理时佩戴防护用具。 - 处理后彻底清洗双手和脸部。 操作处置注意事项： - 避免接触皮肤、眼睛及衣物。 储存条件： - 避免日晒，存放在通风良好的地方。 - 不要暴露在40℃以上的环境中。 - 储存处需加锁，并远离氧化剂等不相容的材料。

制备方法与用途

用途

动物用抗菌药质量稳定，不易产生耐药性和交叉耐药性，在动物体内具有较高的抗菌活性。主要用于治疗畜禽的大肠菌病、霍乱、白痢以及慢性呼吸道感染等疾病。

此外，这类药物还可用于冰箱和制冷机及汽车空调系统的制冷剂，同时在医药和化妆品领域中，也可作为气雾喷射剂使用。

反应信息

• 作为反应物：
  描述：

  1,1,1,2-四氟乙烷 在 盐酸 作用下， -20.16 ℃ 、93.0 kPa 条件下， 生成 1,2,2,2-tetrafluoro-ethyl
  参考文献：
  名称：

  在253–553 K的温度范围内，氯原子与CH2F2，CH3CCl3和CF3CFH2气相反应的动力学

  摘要：

  相对速率技术用于研究930–1200 mbar N 2稀释剂中的标题反应。本工作中测得的反应速率系数由表达式k（Cl + CH 2 F 2）= 1.19×10 -17 T 2 exp（-1023 / T）cm 3分子-1 s -1（253-553）总结。 K），k（Cl + CH 3 CCl 3）= 2.41×10 -12 exp（−1630 / T）cm 3分子-1 s -1（253–313 K）和k（Cl + CF 3 CFH 2）= 1.27×10 -12 exp（-2019 / T）cm 3分子-1 s -1（253-313 K）。关于文献数据讨论了结果。©2009 Wiley Periodicals，Inc.国际化学杂志Kinet 41：401–406，2009

  DOI：

  10.1002/kin.20398
• 作为产物：
  描述：

  三氯乙烯 在 氢氟酸 作用下， 300.0~514.0 ℃ 、101.33 kPa 条件下， 以10%的产率得到1,1,1,2-四氟乙烷
  参考文献：
  名称：

  [EN] CATALYST AND PROCESS USING THE CATALYST FOR MANUFACTURING FLUORINATED HYDROCARBONS
  [FR] CATALYSEUR ET PROCÉDÉ UTILISANT LE CATALYSEUR POUR LA FABRICATION D'HYDROCARBURES FLUORÉS

  摘要：

  一种催化剂，包括一种或多种金属氧化物，其中该催化剂具有总孔体积等于或大于0.3 cm3/g，平均孔径大于或等于90 Å，其中孔体积是使用N2吸附孔隙度法测量的，平均孔径是使用N2 BET吸附孔隙度法测量的。

  公开号：

  WO2018046927A1
• 作为试剂：
  描述：

  (S)-4-isopropyl-3-nitrooxazolidin-2-one 、 正丁胺 在 1,1,1,2-四氟乙烷 作用下， 5.0~20.0 ℃ 、800.01 kPa 条件下， 反应 0.5h， 以77%的产率得到(R)-3-methyl-2-(nitroamino)butyl butylcarbamate
  参考文献：
  名称：

  在液化的1,1,1,2-四氟乙烷介质中合成手性N-硝基-恶唑烷-2-酮和O-（β-硝基氨基烷基）氨基甲酸酯

  摘要：

  摘要 通过在液化的1,1,1,2-中与五氧化二氮中的一个或两个立体生成中心的α-氨基酸衍生的1,3-恶唑烷-2-酮进行硝化反应，方便地合成手性N-硝基-恶唑烷-2-酮已经开发了四氟乙烷介质。通过在相同溶剂中用氨或胺处理，将获得的N-硝基杂环转化为对映体纯的O-（β-硝胺氨基烷基）氨基甲酸酯。合成的N-硝基化合物在体外对人胚肾293（HEK293）细胞有轻微毒性。 出版历史 收到：2020年6月2日 修订后接受：2020年7月13日 发布日期： 2020年8月11日（在线） ©2020年。Thieme。版权所有 Georg Thieme Verlag KGRüdigerstraße14，70469斯图加特，德国

  DOI：

  10.1055/s-0040-1706762

文献信息

• The first early transition metal perfluorovinyl complexes: the synthesis of Cp2M(CFCF2)nX2−n (Cp: η5-C5H5−; M=Ti, Zr; X=Cl or F) and structures of Cp2Ti(CFCF2)nX2−n (X=Cl, F) via Ti K-edge EXAFS studies
  作者：Kulbinder K Banger、Alan K Brisdon

  DOI：10.1016/s0022-328x(99)00073-x

  日期：1999.6

  titanium-containing compounds Ti K-edge EXAFS data have been recorded from which distances for the titanium–carbon bond of the perfluorovinyl group of 2.033(12) and 2.050(18) Å in Cp2Ti(CFCF2)2 and Cp2Ti(CFCF2)F are obtained. This is the first report of structural data for any perfluorovinyl organometallic compound, and the distances obtained are consistent with the perfluorovinyl group binding in a simple

  到的全氟乙烯基化合物中，最近被美国公布一个新的路线，已用于制备类型CP的早过渡金属配合物的第一实施例2 M（CFCF 2）ñ X ñ -2（CP：η 5 -C 5 ħ 5 - ; M =钛，锆; X = Cl或F）。这些化合物是通过HFC-134a（CF 3 CH 2 F）与两当量的BuLi两步一锅反应，然后添加CP 2 MX 2以高收率获得的。（M ＝ Ti，Zr，X ＝ F，Cl）。对于两个含钛化合物的Ti K-边缘EXAFS数据已经从该距离对于全氟乙烯基的2.033（12）和2.050（18）的钛-碳键的中的CP记录的2的Ti（CFCF 2）2 1和CP 2的Ti（CFCF 2获得）F。这是任何全氟乙烯基有机金属化合物的结构数据的首次报道，并且获得的距离与全氟乙烯基以简单的sigma方式结合是一致的。
• NOVEL CATALYTIC METHOD FOR THE PRODUCTION OF FLUOROALKYLENES FROM CHLOROFLUOROHYDROCARBONS
  申请人：Mukhopadhyay Sudip

  公开号：US20060217577A1

  公开（公告）日：2006-09-28

  A process for producing a producing a product of the formula: R—CF═CHR 1 wherein R is F or CF 3 and R 1 is F when R is F and is H when R is CF 3 by reacting a reactant of the formula: CF 3 —R 2 wherein R 2 is selected from wherein R 3 is H, F or Cl and R 4 is H or Cl, in the presence of a suitable catalyst, with a reducing agent selected from methane, methyl chloride and mixtures thereof, in a gas phase reaction.

  生产公式为R—CF═CHR的产品的方法： 其中R为F或CF3，R1在R为F时为F，在R为 时为H， 通过在适当催化剂的存在下，将公式为 —R2的反应物与选择自的还原剂（甲烷、氯化甲基或二者的混合物）在气相反应中反应。
• MANUFACTURING METHOD OF HYDROFLUOROOLEFIN
  申请人：ASAHI GLASS COMPANY, LIMITED

  公开号：US20180037524A1

  公开（公告）日：2018-02-08

  A method for manufacturing hydrofluoroolefin, includes: converting hydrofluorocarbon represented by a formula (1) into hydrofluoroolefin (HFO) represented by formula (2) in the presence of carbon dioxide to obtain a first gas composition containing hydrofluoroolefin and carbon dioxide; and separating carbon dioxide contained in the first gas composition to obtain a second gas composition containing HFO, CR 1 R 2 X 1 CR 3 R 4 X 2 . . . (1), CR 1 R 2 ═CR 3 R 4 . . . (2), wherein R 1 to R 3 are each independently hydrogen atom or fluorine atom, R 4 is hydrogen atom, fluorine atom, CH 3 , CH 2 F, CHF 2 or CF 3 , the total number of fluorine atoms of R 1 to R 4 is one or more, and the total number of hydrogen atoms of R 1 to R 4 is one or more, X 1 and X 2 are each hydrogen atom or fluorine atom where X 2 is the fluorine atom when X 1 is the hydrogen atom, and X 2 is the hydrogen atom when X 1 is the fluorine atom.

  一种制造氢氟烯烃的方法，包括：在二氧化碳存在下，将由式（1）表示的氢氟烃转化为由式（2）表示的氢氟烯烃（HFO），以获得含有氢氟烯烃和二氧化碳的第一气体组成物；并分离第一气体组成物中含有的二氧化碳，以获得含有HFO的第二气体组成物，CR1R2X1CR3R4X2...（1），CR1R2═CR3R4...（2），其中R1至R3分别独立地是氢原子或氟原子，R4是氢原子、氟原子、CH3、CH2F、CHF2或CF3，R1至R4的氟原子总数为一个或多个，R1至R4的氢原子总数为一个或多个，X1和X2分别是氢原子或氟原子，其中当X1为氢原子时，X2为氟原子，当X1为氟原子时，X2为氢原子。
• Structural Characterization of Hydro‐, Chloro‐ and Fluoroorganylsilanes with Substituents of Varying Electron Withdrawing Character
  作者：Mira Keßler、Sven Porath、Hans‐Georg Stammler、Berthold Hoge

  DOI：10.1002/ejic.202001065

  日期：2021.3.12

  We report on the molecular structure of trimethylsilanes Si(CH3)3X in which the substituents X, namely (Z)‐pentafluoropropen‐1‐yl, trifluoropropyn‐1‐yl, pentafluoroethyl, trifluorovinyl, vinyl, propyn‐1‐yl, di‐ and trichloromethyl, display electron withdrawing effects of varying strength. The lengths of the bonds between the silicon and the carbon atoms of X correlate with the hybridization of the

  我们报告了三甲基硅烷Si（CH 3）3 X的分子结构，其中的取代基X为（Z）-五氟丙烯-1-基，三氟丙炔-1-基，五氟乙基，三氟乙烯基，乙烯基，丙炔-1-基，二氯和三氯甲基，显示出不同强度的电子吸收效应。X的硅和碳原子之间的键的长度与各个轨道的杂化和X的空间需求相关，而不与电子吸收能力相关。在氯化取代基的情况下，分散效应似乎会缩短Si-C键。此外，还有一种从致冷剂2,3,3,3-四氟丙烯（HFO-1234yf）和n生成三氟丙炔-1-基锂的途径描述了丁基锂。四氟丙烯-1-基锂在-80°C时缓慢形成，但即使在此温度下，也会自发消除LiF。所形成的3,3,3-三氟丙炔的去质子化需要高于-60°C的温度，从而导致三氟丙炔-1-基锂在室温下相对稳定。
• Synthesis, Structure, and Solution Behavior of 1-Chloro-2,2-difluorovinyl Titanocene Derivatives:  The First X-ray Study of a Titanium Fluorovinyl Compound and Spectroscopic Elucidation of the [Cp₂TiMe(η²-CF₂CClH)] Complex
  作者：Nicholas A. Barnes、Alan K. Brisdon、Ian R. Crossley、Robin G. Pritchard、John E. Warren

  DOI：10.1021/om0499254

  日期：2004.5.1

  The first early-transition-metal 1-chloro-2,2-difluorovinyl complexes [Cp2TiXn(CClCF2)2-n] (X = Cl, F; n = 0, 1) have been synthesized by the low-temperature reaction of Cp2TiX2 (X = Cl, F) with (1-chloro-2,2-difluorovinyl)lithum, generated in situ from HCFC-133a (CF3CH2Cl) and n-butyllithium. The complexes have been characterized by spectroscopy and, in the case of [Cp2TiCl(CClCF2)], by single crystal

  第一早期-过渡金属1-氯-2,2-二氟络合物的[Cp 2 TIX Ñ（CCL CF 2）2 - Ñ ]（X =氯，氟; Ñ = 0,1）已经由合成低Cp 2 TiX 2（X = Cl，F）与（1-氯-2,2-二氟乙烯基）锂的高温反应，是由HCFC-133a（CF 3 CH 2 Cl）和正丁基锂原位生成的。配合物已通过光谱学表征，在[Cp 2 TiCl（CCl CF 2）]，通过单晶X射线衍射，使其成为第一个具有结构特征的钛基氟乙烯基化合物。已经探究了这些材料明显的固溶相不稳定性，以试图确定可能导致系统稳定的关键特性。为此，所述化合物的[Cp *的合成2的TiF Ñ（CF CF 2）2 - Ñ（Ñ = 0，1）和混合[Cp 2时间（CCL CF 2）]已经报道和他们的稳定性进一步调查。在[Cp 2 TiMe（CCl CF 2）]，这导致了该π络合物[Cp的光谱表征2时间（η 2 -CF 2

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