溴氯甲烷 | 74-97-5

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 卤代烷
• 中文名称: 溴氯甲烷
• 中文别名: 氯溴甲烷；1-氯-1-溴甲烷；氯溴次甲基
• 英文名称: chlorobromomethane
• 英文别名: Bromochloromethane；bromo(chloro)methane
• CAS: 74-97-5
• 化学式: CH₂BrCl
• 分子量: 129.384
• InChiKey: JPOXNPPZZKNXOV-UHFFFAOYSA-N

物化性质

• 熔点：
  -87.9 °C
• 沸点：
  68.0 °C
• 密度：
  1.9344 g/cm3
• 物理描述：
  Bromochloromethane appears as a clear colorless liquid with a sweet chloroform-like odor. Denser than water (density 1.991 g / cm3) and insoluble in water. Hence sinks in water. Boiling point 68°C. Vapors may cause illness if inhaled. Nonflammable. When exposed to high temperatures may emit toxic fumes. Used as a fire extinguishing agent.
• 颜色/状态：
  Clear, colorless liquid
• 气味：
  2100 mg/cu m (odor threshold low); 2100 mg/cu m (odor threshold high) sweet.
• 闪点：
  No flash or fire points by standard tests in air.
• 溶解度：
  In water, 1.67X10+4 mg/L at 25 °C
• 蒸汽密度：
  4.46 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  142 mm Hg at 25 °C
• 大气OH速率常数：
  8.80e-14 cm3/molecule*sec
• 稳定性/保质期：
  1. 稳定性[18]：稳定。 2. 禁配物[19]：强氧化剂、强碱、碱金属。 3. 聚合危害[20]：不聚合。 4. 分解产物[21]：氯化氢、溴化氢。
• 分解：
  Toxic gases & vapors (such as hydrogen chloride, phosgene, carbon monoxide, & hydrogen bromide) may be released when chlorobromomethane decomposes.
• 粘度：
  0.670 mN.s/sq m at 20 °C
• 腐蚀性：
  Liquid bromochloromethane will attack some forms of plastics, rubber, and coatings.
• 汽化热：
  232 J/g (55.4 cal/g) at boiling point
• 表面张力：
  33.32 dynes/cm at 20 °C
• 电离电位：
  10.77 eV
• 折光率：
  Index of refraction: 1.4838 at 20 °C/D
• 保留指数：
  602;607;611;559.9;595.8;598;598;600.4

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  3
• 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：
  0

ADMET

代谢

血液中的无机溴化物和尿液中的无机溴化物是在暴露于空气中1000 ppm氯甲溴的狗身上确定的。这些动物每天暴露7小时，每周5天。在第三周，血清中的无机溴化物从正常的5至10毫克/100毫升增加到超过200毫克。在第13周和第14周，浓度超过了每100毫升血液300毫克的无机溴化物。... 挥发性溴化物的浓度被确定，以每100毫升血液中毫克氯甲溴的形式表示。在暴露结束时立即采集，观察到每100毫升血液中有5至9毫克的氯甲溴浓度。在最后一次暴露结束后的17-65小时内，一只狗中没有观察到挥发性溴化物，另一只狗中的浓度小于1毫克。似乎氯甲溴在空气中暴露于蒸汽时出现在血液中，但在暴露停止后会迅速消失。显然，大量的物质被水解或代谢生成无机溴化物...。

... Inorganic bromide in blood serum and urine /was determined/ in dogs exposed to 1000 ppm of methylene chlorobromide in air. These animals were exposed 7 hr/day, 5 days/week. During the third week, the serum inorganic bromide had increased from a normal of 5 to 10 mg/100 mL to >200 mg. By the 13th and 14th weeks, the concentration was greater than 300 mg of inorganic bromide per 100 mL of blood. ... The ... concentration of volatile bromide /was determined/ expressed as milligrams of methylene chlorobromide per 100 mL of blood. Taken immediately at the end of the exposure, concentrations between 5 and 9 mg of methylene chlorobromide per 100 mL were observed. At periods of 17-65 hr after the end of the last exposure, no volatile bromide was observed in one dog and concentrations of <1 mg in the other. It would appear that methylene chlorobromide as such appears in the blood during exposure to vapors in air, but disappears rapidly on cessation of exposure. Apparently, a significant amount of material is hydrolyzed or metabolized to yield inorganic bromide ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

二氯甲烷（甲基氯，DCM）和其他的二卤代甲烷会被代谢为一氧化碳（CO），这种气体可以可逆地与血红蛋白结合并通过呼出而排出体外。我们已经开发了一个基于生理学的药物动力学（PB-PK）模型，该模型描述了CO、碳氧血红蛋白（HbCO）和母体二卤代甲烷的动力学，并应用这个模型来检查大鼠和人类吸入CO和DCM的动力学。模型中描述CO和HbCO动力学的部分是根据Coburn-Forster-Kane方程改编的，在修改后包括了DCM氧化产生CO的过程。DCM的动力学和代谢用一个通用的挥发性化学物质PB-PK模型来描述……首先通过将大鼠暴露于200 ppm的CO中2小时，然后检查停止CO暴露后HbCO的时间过程来估计CO的生理和生化常数。这些CO吸入研究提供了在自由呼吸下CO扩散能力和Haldane系数的估计，即血红蛋白在CO和O2之间的相对平衡分布比率。然后将CO模型与DCM的PB-PK模型相结合，以预测大鼠在DCM暴露期间和暴露后HbCO时间过程的行为。通过结合模型，可以估计出DCM氧化产生CO的产量。在大鼠中，每摩尔DCM氧化大约只产生0.7摩尔CO。组合模型充分代表了在4小时内暴露于200或1000 ppm DCM后HbCO和DCM的行为，以及暴露于5160 ppm DCM或5000 ppm溴氯甲烷1/2小时后HbCO的行为。大鼠PB-PK模型被调整以预测人类暴露于DCM或CO时DCM、HbCO和CO的动力学。从文献中检查了三个人类数据集：(1)吸入50、100、250和500 ppm CO；(2)七次1/2小时吸入50、100、250和500 ppm DCM；(3)2小时吸入986 ppm DCM。这里首次报告了一组人类志愿者暴露于100或350 ppm DCM 6小时的新数据集。在每个研究中，根据需要调整内源性CO产生速率和血液室中CO的初始量，以给出基线HbCO值，该值从小于0.5%到大于2% HbCO不等。组合PB-PK模型在所有四个人类研究中都很好地代表了观察到的行为。

Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide (CO) which reversibly binds hemoglobin and is eliminated by exhalation. We have developed a physiologically based pharmacokinetic (PB-PK) model which describes the kinetics of CO, carboxyhemoglobin (HbCO), and parent dihalomethane, and have applied this model to examine the inhalation kinetics of CO and of DCM in rats and humans. The portion of the model describing CO and HbCO kinetics was adapted from the Coburn-Forster-Kane equation, after modification to include production of CO by DCM oxidation. DCM kinetics and metabolism were described by a generic PB-PK model for volatile chemicals ... Physiological and biochemical constants for CO were first estimated by exposing rats to 200 ppm CO for 2 hr and examining the time course of HbCO after cessation of CO exposure. These CO inhalation studies provided estimates of CO diffusing capacity under free breathing and for the Haldane coefficient, the relative equilibrium distribution ratio for hemoglobin between CO and O2. The CO model was then coupled to a PB-PK model for DCM to predict HbCO time course behavior during and after DCM exposures in rats. By coupling the models it was possible to estimate the yield of CO from oxidation of DCM. In rats only about 0.7 mol of CO are produced from 1 mol of DCM during oxidation. The combined model adequately represented HbCO and DCM behavior following 4-hr exposures to 200 or 1000 ppm DCM, and HbCO behavior following 1/2-hr exposure to 5160 ppm DCM or 5000 ppm bromochloromethane. The rat PB-PK model was scaled to predict DCM, HbCO, and CO kinetics in humans exposed either to DCM or to CO. Three human data sets from the literature were examined: (1) inhalation of CO at 50, 100, 250, and 500 ppm; (2) seven 1/2-hr inhalation exposures to 50, 100, 250, and 500 ppm DCM; and (3) 2-hr inhalation exposures to 986 ppm DCM. An additional data set from human volunteers exposed to 100 or 350 ppm DCM for 6 hr is reported here for the first time. Endogenous CO production rates and the initial amount of CO in the blood compartment were varied in each study as necessary to give the baseline HbCO value, which varied from less than 0.5% to greater than 2% HbCO. The combined PB-PK model gave a good representation of the observed behavior in all four human studies.

来源:Hazardous Substances Data Bank (HSDB)

代谢

体内代谢常数在雄性Fischer大鼠中确定了五种化学物质：1,1-二氯乙烯（1,1-DCE）、乙醚（DE）、溴氯甲烷（BCM）、甲基氯甲烷（MC）和四氯化碳（CCl4）。使用封闭循环暴露系统收集了每种化学物质在不同初始浓度下的一系列摄取曲线。这些曲线的形状是组织分配系数和这些化学物质代谢的动力学特征的功能。实验确定了每种化学物质的组织：空气分配系数，并将其纳入生理动力学模型中，然后用于模拟摄取过程。通过调整化学物质代谢的生物化学常数，获得了每种化学物质摄取曲线族的优化拟合。1,1-DCE和CCl4的代谢都由单一的饱和过程表示，而MC只需要一级反应途径。BCM和DE表现出饱和和一级反应过程的结合。吡唑醇阻断了氧化微粒体代谢，抑制了1,1-DCE、BCM、DE和CCl4代谢的饱和途径，并消除了MC的一级反应途径。对于225克的鼠，1,1-DCE、BCM、DE和CCl4饱和途径的代谢最大速度分别为27.2、19.9、26.1和0.92摩尔/小时。分析气体摄取数据的模拟方法区分单一和多种代谢途径，并提供可以在预测毒动学模型中使用的动力学常数，用于描述持续浓度吸入暴露以及其他管理途径的暴露。

In vivo metabolic constants were determined in male Fischer rats for five chemicals: 1,1-dichloroethylene (1,1-DCE), diethyl ether (DE), bromochloromethane (BCM), methyl chloroform (MC), and carbon tetrachloride (CCl4). A closed recirculated exposure system was used to collect a series of uptake curves for each chemical at a range of initial concentrations. The shapes of these curves were a function of the tissue partition coefficients and the kinetic characteristics of the metabolism of these chemicals. Tissue:air partition coefficients were experimentally determined for each chemical and incorporated into a physiological kinetic model which was then used to simulate the uptake process. An optimal fit of the family of uptake curves for each chemical was obtained by adjusting the biochemical constants for metabolism of the chemical. Metabolism of both 1,1-DCE and CCl4 was represented by a single saturable process while MC required only a first-order pathway. BCM and DE exhibited a combination of both a saturable and a first-order process. Pyrazole, which blocks oxidative microsomal metabolism, inhibited the saturable pathways of 1,1-DCE, BCM, DE, and CCl4 metabolism and abolished the first-order pathway for MC. The maximum velocity of metabolism for the saturable pathway with 1,1-DCE, BCM, DE, and CCl4 for a 225-g rat was 27.2, 19.9, 26.1, and 0.92 mol/hr, respectively. The simulation approach for analyzing gas uptake data distinguishes between single and multiple metabolic pathways and provides kinetic constants that can be used in predictive toxicokinetic models for describing constant concentration inhalation exposure as well as exposures by other routes of administration.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服每公斤体重6.2毫摩尔的一氯甲烷（DCM）、溴氯甲烷（BCM）或溴甲烷（DBM）可分别使碳氧血红蛋白（COHb）水平达到约9%（6小时）、11%（8小时）和22%（12小时）的最大值。在大鼠体内，预先使用异烟肼，4 x 0.36毫摩尔/公斤，腹膜内注射，显著增强了COHb的形成；一氯甲烷后的COHb值为18.0 +/- 0.8%，溴氯甲烷后为24.1 +/- 0.8%，溴甲烷后为39.0 +/- 1.3%。预先使用苯巴比妥，4 x 0.31毫摩尔/公斤，腹膜内注射，对一氯甲烷后的COHb水平没有明显改变，而在溴氯甲烷和溴甲烷后略有但显著的增加。数据表明，卤代甲烷的氧化代谢产生一氧化碳主要是由细胞色素P-450 IIE1催化的，并且一氯甲烷引起的COHb形成似乎是一种测试化学物质是否为这种形式的细胞色素P-450诱导剂的方法。

An oral dose of 6.2 mmoles of diachloromethane (DCM), bromochloromethane (BCM) or dibromomethane (DBM) per kg body mass yielded a maximum carboxyhemoglobin (COHb) level of about 9% (at 6 hr), 11% (at 8 hr) and 22% (at 12 hr), respectively. Pretreatment of rats with isoniazid, 4 x 0.36 mmol/kg i.p., produced significant enhancements of the COHb formation; the values were 18.0 +/- 0.8% COHb after DCM, 24.1 +/- 0.8% COHb after BCM, and 39.0 +/- 1.3% COHb after DBM. Prior administration of phenobarbital, 4 x 0.31 mmol/kg i.p., caused no appreciable alterations in the COHb levels after DCM and slight but significant increases after BCM as well as after DBM. The data indicate that the oxidative metabolism of dihalomethanes to carbon monoxide is mainly catalyzed by cytochrome P-450 IIE1 and that the DCM-evoked COHb formation seems to be a method of testing whether a chemical is an inducer of this form of cytochrome P-450 in vivo.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：氯溴甲烷是一种无色至浅黄色的液体。氯溴甲烷的主要用途是作为灭火剂，特别是用于飞机和便携式系统。它还用作爆炸抑制剂、溶剂，以及在制造一些杀虫剂（如氯甲磷）的中间体。人类暴露和毒性：暴露于氯溴甲烷的症状包括迷失方向、眩晕、皮肤、眼睛和喉咙刺激、肺水肿、头痛、厌食、恶心、呕吐、腹痛、体重减轻、记忆障碍、瘫痪、虚弱、震颤、惊厥和中枢神经系统抑制。它可能导致咳嗽、胸痛和呼吸困难。它还可能导致暂时性的角膜上皮损伤。该化合物对粘膜、上呼吸道、眼睛和皮肤的组织的破坏性极强。一名消防员的角膜在含有氯溴甲烷和二氯二氟甲烷的灭火器近距离喷射到他的脸部时受伤。不久之后观察到部分角膜上皮的损失，但角膜更深层次保持清晰。动物研究：将兔眼暴露于含有75%氯溴甲烷和25%二氯二氟甲烷混合液的灭火器喷射出的液体中，导致暂时性的角膜上皮损伤和结膜水肿。当反复应用于兔子的开放皮肤上时，氯溴甲烷导致一些充血和脱屑。当包扎在皮肤上时，它产生中等程度的刺激和充血。浓度低至3000 ppm时在大鼠中产生轻微的麻醉。在低于27,000 ppm的浓度下观察到暂时性的肺水肿。在更高浓度下，间质性肺炎导致延迟死亡。在20,000 ppm暴露后也观察到延迟死亡。只有在高于27,000 ppm的暴露下，才会在暴露期间发生死亡。在狗身上，急性暴露于高浓度下，12分钟内产生了激动、心律不齐、心肌对肾上腺素的敏感性增加和癫痫样惊厥。氯溴甲烷对含有大鼠谷胱甘肽S-转移酶5-5的沙门氏菌typhimurium菌株TA100和TA1535具有诱变性。在大肠杆菌WU361089暴露于10 uL/板的tyr位点上观察到了反向突变，无需激活。在没有激活的情况下，大肠杆菌K394暴露于10 uL/板也观察到了前噬菌体的诱导。在用中国仓鼠的FAF细胞进行的体外试验中，该化合物增加了姐妹染色单体交换频率。

IDENTIFICATION AND USE: Chlorobromomethane is a colorless to pale-yellow liquid. The major use of chlorobromomethane is as fire-extinguishing fluid, particularly for aircraft and portable systems. It is also used as an explosion suppression agent, as a solvent, and as an intermediate in the manufacture of some insecticides (chlormephos). HUMAN EXPOSURE AND TOXICITY: Symptoms of exposure to chlorobromomethane include disorientation; dizziness; irritation of the skin, eyes and throat; pulmonary edema; headache; anorexia; nausea; vomiting; abdominal pain; weight loss; memory impairment; paralysis; weakness; tremors; convulsions; and CNS depression. It may cause coughing, chest pain, and difficulty in breathing. It may also cause transient corneal epithelium damage. The compound is extremely destructive to tissue of the mucous membranes, upper respiratory tract, eyes, and skin. One firefighter's cornea was injured when a fire extinguisher containing chlorobromomethane and dichlorodifluoromethane was discharged close to his face. Soon thereafter partial loss of corneal epithelium was observed, but deeper layers of cornea remained clear. ANIMAL STUDIES: Exposure of rabbit eyes to a spray of liquid from fire extinguisher containing a mixture of 75% chlorobromomethane plus 25% dichlorodifluoromethane caused transient corneal epithelial injury and conjunctival edema. When applied repeatedly to open skin of rabbits, chlorobromomethane resulted in some hyperemia and exfoliation. When bandaged on, it produced moderate irritation and hyperemia. Concentrations as low as 3000 ppm produced light narcosis in rats. Transient pulmonary edema was observed at concentrations below 27,000 ppm. At higher concentrations, interstitial pneumonitis resulted in delayed deaths. Delayed deaths were also observed after exposure to 20,000 ppm. Deaths during exposure occurred only from exposures above 27,000 ppm. In dogs, acute exposures to high concentrations produced agitation, cardiac arrhythmias, myocardial sensitization to epinephrine, and epileptiform convulsions within 12 min. Chlorobromomethane was mutagenic toward Salmonella typhimurium strains TA100 and TA1535 which contains rat glutathione S-transferase 5-5. Reverse mutations were observed at the tyr locus in Escherichia coli WU361089 exposed at 10 uL/plate without activation. Prophage induction was also observed in E. coli K394 exposed without activation at 10 uL/plate. In an in vitro test with FAF-cells of Chinese hamsters, the compound produced an increase of the sister chromatid exchange frequency.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

分类：D；无法归类为人类致癌性。分类依据：由于缺乏关于溴氯甲烷在人类或动物致癌性的数据；然而，有数据显示存在基因毒性效应，并且与被分类为B2可能人类致癌物的卤代甲烷有结构关系。人类致癌性数据：无。动物致癌性数据：无。

CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Based on the lack of data regarding the carcinogenicity of bromochloromethane in humans or animals; however, there are data indicative of genotoxic effects and structural relationships to halogenated methanes classified as B2 probable human carcinogens. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: None.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过吸入、摄入和皮肤接触被身体吸收。

The substance can be absorbed into the body by inhalation, by ingestion and through the skin.

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

毒理性

• 暴露途径

吸入，吞食，皮肤和/或眼睛接触

inhalation, ingestion, skin and/or eye contact

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 症状

眼睛、皮肤、喉咙刺激；混乱、眩晕、中枢神经系统抑制；肺水肿

irritation eyes, skin, throat; confusion, dizziness, central nervous system depression; pulmonary edema

来源:The National Institute for Occupational Safety and Health (NIOSH)

吸收、分配和排泄

从水中溶液中挥发性有机化学物质（VOCs）的皮肤吸收量的量化是必要的，以理解因皮肤接触受这些化学物质污染的水而可能产生的健康危害。雄性Fischer 344大鼠的背部皮肤（3.1平方厘米）被暴露于14种VOCs的纯溶液、三分之一饱和溶液、三分之二饱和溶液或饱和溶液中24小时。通过植入的颈内导管在暴露期间（0、0.5、1、2、4、8、12和24小时）采集血液样本，并使用气相色谱和顶空分析对VOCs进行分析。在这一系列化学物质中，纯VOCs的吸收量随着水溶性的降低而减少。在24小时暴露于纯化学品期间达到的VOCs血药峰浓度分别为：1,2-二氯乙烷（135.1微克/毫升）、溴氯甲烷（113.3微克/毫升）、氯仿（51.0微克/毫升）、苯（24.2微克/毫升）、四氯乙烯（21.1微克/毫升）、溴甲烷（18.2微克/毫升）、三氯乙烯（11.6微克/毫升）、甲苯（9.5微克/毫升）、二甲苯（8.8微克/毫升）、己烷（8.0微克/毫升）、乙苯（5.6微克/毫升）、苯乙烯（5.3微克/毫升）、四氯化碳（5.0微克/毫升）和1,1,1-三氯乙烷（3.4微克/毫升）。在24小时暴露于纯化学品期间，1,2-二氯乙烷和苯的血药水平继续升高，而其他纯VOCs的血药水平在4小时内达到峰值，然后在暴露期间要么下降，要么保持大致相同。从三分之一、三分之二或饱和的水溶液中吸收VOCs是迅速的，并导致溶液中化学物质的减少，尽管只吸收了少量的水。每种VOC的血药水平与暴露浓度直接相关。VOCs在水溶液中迅速出现在血液中，这表明在仅暴露约1%的大鼠皮肤表面积时，就吸收了可检测的VOCs量。

Quantification of dermal absorption of volatile organic chemicals (VOCs) from aqueous solutions is required to understand the potential health hazards resulting from skin exposure to these chemicals in contaminated water. Male Fischer 344 rats were dermally exposed (3.1-sq cm dorsal skin) to neat, one-third saturated, two-thirds saturated, or saturated aqueous solutions of 14 VOCs for 24 hr. Blood samples were obtained via indwelling jugular catheters during exposure (0, 0.5, 1, 2, 4, 8, 12, and 24 hr), and analyzed for the VOCs by gas chromatography using headspace analysis. Absorption of the neat VOCs in this series of chemicals decreased as water solubility decreased. Peak blood levels of VOCs attained during exposure for 24 hr to neat chemicals were: 1,2-dichloroethane (135.1 ug/mL), bromochloromethane (113.3 ug/mL), chloroform (51.0 ug/mL), benzene (24.2 ug/mL), tetrachloroethylene (21.1 ug/mL), dibromomethane (18.2 ug/mL), trichloroethylene (11.6 ug/mL), toluene (9.5 ug/mL), xylene (8.8 ug/mL), hexane (8.0 ug/mL), ethylbenzene (5.6 ug/mL), styrene (5.3 ug/mL), carbon tetrachloride (5.0 ug/mL), and 1,1,1-trichloroethane (3.4 ug/mL). Blood levels of 1,2-dichloroethane and benzene continued to increase during the 24-hr exposure to neat chemical, while blood levels of the other neat VOCs peaked within 4 hr and then either decreased or remained about the same for the duration of the exposure. Absorption of VOCs from one-third, two-thirds, or saturated aqueous solutions was rapid, and resulted in depletion of the chemical from the solution although only a small amount of water was absorbed. Blood levels of each VOC were directly related to the exposure concentrations. The rapid appearance of VOCs in the blood from aqueous solutions demonstrates that detectable amounts of VOCs were absorbed during exposure of only about 1% of the skin surface area of the rat.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

化学蒸气通过皮肤的吸收是一个被动过程，不容易量化，但在某些职业环境中评估健康危害可能很重要。生理建模是一种定量技术，可以提供对被建模系统的洞察，并且可以用于种间外推。我们开发了一个生理模型，用于预测有机蒸气在活体中通过皮肤的渗透，该模型允许在已知化学分布系数、生理和代谢参数以及皮肤渗透性常数的情况下，预测大鼠在皮肤蒸气暴露后的血液浓度。我们以两种不同的方式使用该模型。首先，通过使用一种基于生理学的二卤代甲烷药物代谢动力学模型，计算出二溴甲烷（DBM）、溴氯甲烷（BCM）和二氯甲烷（DCM）的渗透性常数，将皮肤蒸气暴露期间的血液浓度与通过皮肤吸收的化学物质总量相关联。其次，在模型中增加了一个皮肤室，其输入基于渗透性-面积-浓度乘积。这个预测模型充分描述了在宽浓度范围内DBM、BCM和DCM皮肤蒸气暴露后的血液浓度。这个模型可以很容易地修改用于其他有机蒸气，并且可以通过替换动物值为人类生理参数来外推到人类蒸气暴露条件，只要渗透性常数已知或可以被确定。

Absorption of chemical vapors through the skin is a passive process that is not easily quantitated, but may be important in the assessment of health hazards in some occupational circumstances. Physiological modeling is a quantitative technique which may provide insight into the system being modeled and can be used for interspecies extrapolation. We developed a physiological model for the penetration of organic vapors through skin in vivo which allows the prediction of blood concentrations, after dermal vapor exposures in the rat, when chemical distribution coefficients, physiological and metabolic parameters, and skin permeability constants are known. We used the model in two distinct ways. First, permeability constants for dibromomethane (DBM), bromochloromethane (BCM), and methylene chloride (DCM) were calculated by using a physiologically based pharmacokinetic model for dihalomethanes to relate blood concentrations during dermal vapor exposures to the total amount of chemical which was absorbed through the skin. Second, a skin compartment was added to the model which had input based on the permeability-area-concentration product. This predictive model adequately described blood concentrations after DBM, BCM, and DCM dermal vapor exposures over a wide range of concentrations. This model could easily be modified for use with other organic vapors, and could be used to extrapolate to human vapor exposure conditions by substituting human physiological parameters for the animal values, providing permeability constants are known or can be determined.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

二溴甲烷（DBM）和溴氯甲烷（BCM）蒸气的皮肤吸收在置于特制实验舱的大鼠中进行研究，该实验舱配有个人呼吸防护装置，以避免肺吸入。暴露浓度分别为DBM 500至10,000 ppm；BCM 2500至40,000 ppm，持续4小时，在此期间通过颈静脉导管取五次血样，用于气相色谱分析原始的二元卤代甲烷。根据血液中的浓度、组织分配系数、组织体积和通气率估算储存于组织和呼出的化学物质的数量。通过4小时暴露期间释放的溴化物的量来估算总代谢量。通过估算血液和组织中的原始化学物质的数量，以及呼出和代谢的量，计算出通过皮肤吸收的蒸气总量。通过将吸收的量除以暴露表面积和暴露持续时间，计算出每种浓度的皮肤通量（DBM：0.004至0.078 mg/平方厘米/小时；BCM：0.011至0.164 mg/平方厘米/小时）。将通量除以暴露浓度，计算出渗透常数。对于每种二元卤代甲烷，渗透常数（DBM：约1.12 cm/小时；BCM：约0.79 cm/小时）基本上与暴露浓度无关。这项研究显示，在啮齿动物中进行全身皮肤蒸气暴露在技术上是有可能的，并且可以通过基于实现的血液浓度和一些代谢量的计算来量化渗透。

The dermal absorption of dibromomethane (DBM) and bromochloromethane (BCM) vapors was studied in rats placed in a specially designed chamber incorporating individual respiratory protection to avoid pulmonary uptake. Exposures (DBM: 500 to 10,000 ppm; BCM: 2500 to 40,000 ppm) lasted 4 hr during which time five blood samples were drawn from jugular cannulae for analysis of the parent dihalomethane by gas chromatography. Estimates of the amounts of chemicals stored in tissues and exhaled were based on concentrations in the blood and tissue partition coefficients, tissue volumes, and ventilation rate. Total metabolism was estimated from the amount of bromide released during the 4-hr exposure. The total amount of vapor absorbed through the skin was calculated from the estimates of the amount of parent chemical in blood and tissues, and the amounts exhaled and metabolized. The dermal flux for each concentration (DBM: 0.004 to 0.078 mg/sq cm/hr; BCM: 0.011 to 0.164 mg/sq cm/hr) was calculated by dividing the amount absorbed by exposed surface area and duration of exposure. Flux was divided by exposure concentration to calculate a permeability constant. With each dihalomethane the permeability constants (DBM: congruent to 1.12 cm/hr; BCM: congruent to 0.79 cm/hr) were essentially independent of exposure concentration. This study shows that a whole-body dermal vapor exposure in rodents is technically possible, and quantitation of penetration can be accomplished using calculations based on achieved blood concentrations and some measure of metabolism.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

溴氯甲烷（BCM）是一种挥发性化合物，是水通过氯化消毒的副产品。生理学基础的药代动力学（PBPK）模型被用于风险评估应用。一个更新的BCM的PBPK模型被生成并应用于使用蒸气吸收数据校准的假设检验。检验的两种不同的代谢假设是（1）一个使用CYP2E1和谷胱甘肽转移酶两种酶的两途径模型，（2）一个双结合位点模型，其中代谢可以在一个酶CYP2E1上发生。我们的计算机模拟显示，两种假设都以相似的方式描述实验数据。两种途径的结果与先前报道的值相当（V(max)=3.8 mg/hr，K(m)=0.35 mg/L，k(GST)=4.7 /hr）。双结合位点结果为V(max(1))=3.7 mg/hr，K(m(1))=0.3 mg/hr，CL(2)=0.047 L/hr。此外，我们使用获得的优化值探讨了每个模型不同参数的敏感性。

Bromochloromethane (BCM) is a volatile compound and a by-product of disinfection of water by chlorination. Physiologically based pharmacokinetic (PBPK) models are used in risk assessment applications. An updated PBPK model for BCM is generated and applied to hypotheses testing calibrated using vapor uptake data. The two different metabolic hypotheses examined are (1) a two-pathway model using both CYP2E1 and glutathione transferase enzymes and (2) a two-binding site model where metabolism can occur on one enzyme, CYP2E1. Our computer simulations show that both hypotheses describe the experimental data in a similar manner. The two pathway results were comparable to previously reported values (V(max)=3.8 mg/hr, K(m)=0.35 mg/L, and k(GST)=4.7 /hr). The two binding site results were V(max(1))=3.7 mg/hr, K(m(1))=0.3 mg/hr, CL(2)=0.047 L/hr. In addition, we explore the sensitivity of different parameters for each model using our obtained optimized values.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26,S36/37,S37/39,S39,S45,S59
• 危险类别码：
  R59,R36/37/38,R20
• WGK Germany：
  2
• 海关编码：
  2903799090
• 危险品运输编号：
  UN 1887 6.1/PG 3
• 危险类别：
  6.1(b)
• RTECS号：
  PA5250000
• 包装等级：
  III
• 储存条件：
  储存注意事项：应将物品存放在阴凉、通风的库房中，远离火源和热源，并确保容器密封。避免与碱金属及食用化学品混放，切勿混合储存。储区需配备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

制备方法适用于浸渍涂装或淋幕涂装作业的烘漆体系所产生的气泡。

用途简介暂无详细内容。

用途包括：

1. 用作小型灭火剂。
2. 还可用于矿物浮选和作为涂料的渗透剂。 [23]

反应信息

• 作为反应物：
  描述：

  溴氯甲烷 在 氯仿 作用下， 反应 24.0h， 生成 二氯甲烷
  参考文献：
  名称：

  Method of Converting a Brominated Hydrocarbon to a Chlorinated Hydrocarbon

  摘要：

  本发明提供了一种将溴化碳氢转化为氯化碳氢的方法，涉及将溴化碳氢和含水量小于或等于30重量百分比的氯化离子交换树脂一起接触。其中，所述含水量是基于氯化离子交换树脂和水的总重量。溴化碳氢包括至少一个可替换的溴基团，其中每个可替换的溴基团独立地共价键合到一个sp3杂化碳上。溴化碳氢与氯化离子交换树脂之间的接触导致将溴化碳氢中的至少一个可替换的溴基团替换为氯基，并相应地将至少一部分溴化碳氢转化为氯化碳氢。

  公开号：

  US20210047250A1
• 作为产物：
  描述：

  二氯甲烷 在 aluminum tri-bromide 作用下， 反应 4.0h， 以3.5 mmol的产率得到溴氯甲烷
  参考文献：
  名称：

  由芳基氟硼酸钾合成含氟芳基硼烷

  摘要：

  通过在温和的条件下使硼和氯化铝与溴化物与芳基三氟硼酸钾K [ArBF 3 ]反应，可获得含氟的芳基二卤化硼烷。以类似的方式，通过与K [（C 6 F 5）2 BF 2 ]的反应合成了双（五氟苯基）卤代硼烷。K [C 6 F 5 BF 3 ]与AlBr 3的反应产生C 6 F 5 BF 2和C 6 F 5 BCl 2的混合物，这是由于AlBr 3快速转化为AlBrCl2。计算了BCl 2和BBr 2组的感应和共振参数。

  DOI：

  10.1134/s1070363220010089
• 作为试剂：
  描述：

  {[2-(S)-amino-3-(3,4-dihydroxy-phenyl)-propionyl]-methyl-amino}-acetic acid methyl ester 、 3-甲酰基吲哚酸-1-羧酸 t-丁基酯 在 溴氯甲烷 、 sodium acetate 、 caesium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 (5s,9aS)-5-(1H-indol-3-yl)-8-methyl-7,8,9a,10-tetrahydro-5H-1,3-dioxa-5a,8-diaza-cyclopenta[b]anthracene-6,9-dione
  参考文献：
  名称：

  通过Pictet-Spengler方法合成C-1吲哚-3-基取代的四氢异喹啉衍生物

  摘要：

  提出了通过Pictet-Spengler缩合与L -DOPA或1- DOPA衍生物和1 H-吲哚-3-甲醛进行非对映选择性合成C-1吲哚-3-基取代的四氢异喹啉衍生物的方案。该方案用于成功合成几种四氢异喹啉以及二酮哌嗪融合的类似物。

  DOI：

  10.1016/j.tetlet.2012.07.017

文献信息

• Alleno-Acetylenic Cage (AAC) Receptors: Chiroptical Switching and Enantioselective Complexation of<i>trans</i>-1,2-Dimethylcyclohexane in a Diaxial Conformation
  作者：Cornelius Gropp、Nils Trapp、François Diederich

  DOI：10.1002/anie.201607681

  日期：2016.11.7

  (AACs) are highly conformation sensitive, the longest wavelength Cotton effect at 304 nm switches from Δϵ=+191 m−1 cm−1 for open (P)4‐AAC⊂acetonitrile to Δϵ=−691 m−1 cm−1 (ΔΔϵ=882 m−1 cm−1) for closed (P)4‐AAC⊂cyclohexane. Complete chiral resolution of (±)‐trans‐1,2‐dimethylcyclohexane was found in the X‐ray structures, with (P)4‐AAC exclusively bound to the (R,R)‐ and (M)4‐AAC to the (S,S)‐guest. Guest

  四个带有OH末端的对映纯1,3-二乙炔基（DEA）被连接在间苯二酚[4]芳烃空洞的边缘上。该系统在由圆形H键阵列封闭的笼形和开放式之间进行构象转换，叔醇基向外延伸。笼型在非极性溶剂中占主导地位，在小极性溶剂中呈开放构象。在溶液和X射线共晶结构中都确认了这两种状态。异炔乙炔笼（AAC）的ECD光谱对构象高度敏感，最长波长在304 nm处的棉花效应从开放的（P）4 -AAC乙腈的Δϵ = + 191  m -1  cm -1切换到Δϵ = −691  m -1 厘米-1（ΔΔ ε = 882 米-1 厘米-1），用于封闭（P）4 -AAC⊂cyclohexane。在X射线结构中发现了（±）-反-1,2-二甲基环己烷的完全手性拆分，其中（P）4- AAC仅与（R，R）-和（M）4- AAC结合（S，S）-访客。客体夹杂物以较高能量的双轴构象发生。
• Rhodium-Catalyzed Regiodivergent Synthesis of Alkylboronates via Deoxygenative Hydroboration of Aryl Ketones: Mechanism and Origin of Selectivities
  作者：Bing Zhang、Xin Xu、Lei Tao、Zhenyang Lin、Wanxiang Zhao

  DOI：10.1021/acscatal.1c02685

  日期：2021.8.6

  available ketones. Mechanistic studies suggest that this Rh-catalyzed deoxygenative borylation of ketones goes through an alkene intermediate, which undergoes regiodivergent hydroboration to afford linear and branched alkylboronates. The different steric effects of PPh2Me and P(nBu)3 were found to be responsible for product selectivity by density functional theory calculations. The alkene intermediate

  在这里，我们报告了一种有效的铑催化酮脱氧硼酸化合成烷基硼酸酯，其中区域选择性可以通过选择配体来切换。直链烷基硼酸酯仅在 P( n Bu) 3存在下获得，PPh 2 Me 有利于支链烷基硼酸酯的形成。该协议还允许从现成的酮中获取 1,1,2-三硼酸酯。机理研究表明，这种 Rh 催化的酮类脱氧硼酸化反应经过烯烃中间体，该中间体经历区域发散硼氢化反应，得到直链和支链烷基硼酸酯。PPh 2 Me 和 P( n Bu) 3的不同空间位阻效应通过密度泛函理论计算发现是产物选择性的原因。烯烃中间体也可以依次进行脱氢硼酸化和硼氢化反应以提供三硼酸酯。
• Stereocontrolled Synthesis of 1,5-Stereogenic Centers through Three-Carbon Homologation of Boronic Esters
  作者：Phillip J. Unsworth、Daniele Leonori、Varinder K. Aggarwal

  DOI：10.1002/anie.201405700

  日期：2014.9.8

  Allylic pinacol boronic esters are stable toward 1,3‐borotropic rearrangement. We developed a PdII‐mediated isomerization process that gives di‐ or trisubstituted allylic boronic esters with high E selectivity. The combination of this method with lithiation–borylation enables the synthesis of carbon chains that bear 1,5‐stereogenic centers. The utility of this method has been demonstrated in a formal

  烯丙基频哪醇硼酸酯对1,3-硼异向重排是稳定的。我们开发了一种由Pd II介导的异构化工艺，该工艺可产生具有高E 选择性的二或三取代的烯丙基硼酸酯。这种方法与锂化-硼化的结合可以合成具有1,5-立体异构中心的碳链。该方法的效用已在（+）-茉莉素的正式合成中得到了证明。
• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE
  申请人：WAVE LIFE SCIENCES LTD

  公开号：WO2018237194A1

  公开（公告）日：2018-12-27

  The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

  本公开内容提供了合成技术，包括用于立体选择性合成的试剂和方法。在某些实施例中，本公开内容提供了作为手性辅助剂有用的化合物。在某些实施例中，本公开内容提供了用于寡核苷酸合成的试剂和方法。在某些实施例中，本公开内容提供了用于手性控制寡核苷酸制备的试剂和方法。在某些实施例中，本公开内容的技术特别适用于构建具有挑战性的核苷酸间连接，提供高产率和立体选择性。
• Radical-Hydroboration-Involved One-Pot Synthesis of Boron-Handled Glycol Derivatives
  作者：Feng-Lian Zhang、Yi-Feng Wang、Bi-Yang Zhuang、Ji-Kang Jin

  DOI：10.1055/s-0040-1707142

  日期：2021.3

  A one-pot two-step protocol for the direct synthesis of boron-handled glycol derivatives is reported. The procedure starts by an NHC–boryl-radical-promoted regioselective hydroboration of glycol-protected cinnamaldehydes. After that, the reaction mixture is treated with pinacol in the presence of HCl, leading to the direct formation of pinacol boronate handled glycol monoalkyl ethers. In this acid-triggered

  报告了直接合成硼处理的乙二醇衍生物的一锅两步协议。该过程从乙二醇保护的肉桂醛的 NHC-硼基自由基促进的区域选择性硼氢化反应开始。之后，反应混合物在 HCl 存在下用频哪醇处理，导致直接形成频哪醇硼酸酯处理的二醇单烷基醚。在这种酸引发的转化中，乙二醇衍生的缩醛部分发生还原性开环，在此期间 NHC-硼烷单元作为氢化物源。

表征谱图