Vinylidene chloride, stabilized appears as a clear colorless liquid with a chloroform-like odor. Flash point 0°F. Boiling point 99°F. Denser (at 10.1 lb / gal) than water and insoluble in water. Hence sinks in water. May polymerize exothermically if heated or contaminated. If the polymerization takes place inside a container, the container may rupture violently. Vapors heavier than air.
Hazardous decomposition products formed under fire conditions - Carbon oxides, hydrogen chloride gas.
粘度：
0.3302 cP at 20 °C
腐蚀性：
Vinylidene chloride may be corrosive or unstable in the presence of steel.
燃烧热：
1095.9 kJ/mole at 25 °C
汽化热：
26.48 kJ/mole at 25 °C
表面张力：
24 dynes/cm at 15 °C (Inhibited)
电离电位：
10.00 eV
聚合：
When stored between -40 and +25 °C in the absence of inhibitor and in presence of air, vinylidene chloride rapidly absorbs oxygen with formation of a violently explosive peroxide. The latter initiates polymerization, producing an insoluble polymer which adsorbs the peroxide. Separation of this polymer in a dry state must be avoided, since if more than 15% of peroxide is present, the polymer may be detonable by slight shock or heat.
气味阈值：
Odor threshold (air) = 2000-5500 mg/cu m
折光率：
Index of refraction: 1.4249 at 20 °C/D
相对蒸发率：
... The evaporation half-life of a dilute aqueous solution of vinylidene chloride (1 ppm w/w) in an open container stirred at 200 rpm at 25 °C /was/ 22 min, 90% of the compound was lost in 89 min.
In recent years, the mechanisms of biotransformation, which often provide the basis for renal toxicity, have been elucidated for a variety of compounds. ... Vinylidene chloride (VDC) is nephrotoxic in mice after inhalation, but not after oral or intraperitoneal administration. The nephrotoxicity of VDC is due to the selective expression of an androgen-dependent cytochrome P450 in the proximal tubules of male mice. This enzyme oxidizes VDC to an electrophile and is not present in female mice, but can be induced be androgen treatment. The observation of nephrotoxicity of VDC after inhalation only is due to the high blood flow to the kidney and thus high concentrations of VDC delivered to the kidney after inhalation. After oral or intraperitoneal application, hepatic first-pass metabolism efficiently reduces the amount of VDC delivered to the kidney...
The proposed metabolic pathways for 1,1-DCE ... were determined from experimental studies in laboratory animals. It is not known whether the metabolism of 1,1-DCE is the same in humans, although in vitro microsomal preparations from human liver and lung form the same initial products ... . Oxidation of 1,1-DCE by CYP2E1 should produce three metabolites: DCE epoxide, 2-chloroacetyl chloride, and 2,2-dichloroacetaldehyde. All of these metabolites react with glutathione (GSH) and/or water. In the kidney, further metabolism of S-(2,2-dichloro-1- hydroxy)ethylglutathione could form another toxic compound, dicholorothioketene. The GSH conjugates formed are catabolized in the kidney to a variety of urinary excretion products. The epoxide, and perhaps to a lesser extent the chloroacetaldehyde, are believed to be associated with the tissue reactivity and toxic effects in tissues that ensue after significant depletion of GSH. The primary metabolites of 1,1-DCE formed in rat hepatic microsomal incubations are DCE epoxide, 2,2-dichloroacetaldehyde, and 2-chloroacetyl chloride ... . These metabolites were also identified from mouse microsomal incubations ... . All these electrophilic metabolites undergo secondary reactions, including oxidation, conjugation with GSH, and hydrolysis. The major products formed are GSH conjugates, 2-(S-glutathionyl)acetyl glutathione, and 2-S-glutathionyl acetate, which are believed to be derived from the DCE epoxide. S-(2,2-Dichloro-1-hydroxy ethyl glutathione, the GSH conjugate formed from reaction of GSH with 2,2- dichloroacetaldehyde, was not observed in rat liver microsomal incubations containing GSH ... . The acetal, together with chloroacetic acid and S-(2-chloroacetyl)- glutathione - the hydrolysis and GSH-conjugated products of 2-chloroacetyl chloride, respectively - was detected at levels much lower than those for the DCE epoxide-derived conjugates.
In human liver and lung microsomal incubations, the DCE epoxide-derived GSH conjugates ...were the major metabolites detected ... . 2,2-Dichloroacetaldehyde was detected at low levels. Liver microsomes from three out of five human samples metabolized 1,1-DCE to the epoxide-derived GSH conjugates at levels that were 2.5- to 3-fold higher than in mouse liver microsomes, based on milligrams of microsomal protein. These GSH conjugates were also the major products formed in lung microsomes from eight human samples; only low levels of 2,2-dichloroacetaldehyde were formed. The mean level in lung microsomes from humans was about 50% of the amount formed in lung microsomes from mice. In both animal and human tissues, cytochrome P450 CYP2E1 catalyzes the formation of the DCE epoxide.
The primary metabolites of 1,1-dichloroethylene (DCE) formed in lung and liver microsomal incubations have been identified as DCE-epoxide, 2,2-dichloroacetaldehyde and 2-chloroacetyl chloride. All are electrophilic metabolites that form secondary reactions including conjugation with GSH. Results ... indicated that the DCE-epoxide is the major metabolite forming conjugates with GSH, and this reaction is likely responsible for the depletion of GSH observed in vivo. /These/ findings support the premise that, following depletion of intracellular GSH, metabolites of DCE including the DCE-epoxide bind to cellular proteins, a process which leads to cell damage and suggests that conjugation with the thiol nucleophile represents a-detoxification mechanism.
1,1-Dichloroethene is absorbed via oral, inhalation, and dermal routes. It is rapidly distributed in the body, mainly to the liver and kidneys. Hepatic microsomal cytochrome P-450 enzymes metabolize 1,1-dichloroethene into its toxic metabolites, which include epoxides, acyl chlorides, and halogenated aldehydes. The main metabolites are believed to be 2,2-dichloroacetaldehyde and 2-chloroacetyl chloride. These are later detoxified by hydroxylation and conjugation with glutathione. Excretion of 1,1-dichloroethene metabolites occurs primarily in the urine and exhaled air. (L185)
IDENTIFICATION AND USE: 1,1-Dichloroethene (1,1-DCE) is a colorless liquid. It is used as a captive intermediate in the production of hydrochlorofluorocarbons (HCFC-141b and HCFC-142b), in the production of chloroacetyl chloride, and in the production of homo-, co-, and terpolymers (latex and resin). The polymers are used in a variety of consumer products, including food packaging, textiles, and outdoor furniture. HUMAN STUDIES: Potential symptoms of overexposure are irritation of eyes, skin, throat, dizziness, headache, nausea, dyspnea, liver and kidney dysfunction, pneumonitis. Acute exposure to high concentrations of 1,1-DCE in air results in CNS depression. Repeated exposures to low concentrations are associated with liver and renal dysfunction. Contact with the eye causes conjunctivitis and transient corneal injury. Skin contact with 1,1-DCE causes irritation, which may be due partly to the presence of an inhibitor, hydroquinone monomethyl ether. In one epidemiological study of 138 workers exposed to 1,1-DCE in the United States, no excess of cancer was found, but follow-up was incomplete, and nearly 40% of the workers had less than 15 years' latency since first exposure. In a study in the Federal Republic of Germany of 629 workers exposed to 1,1-DCE, seven deaths from cancer (five bronchial carcinomas) were reported. This number was not in excess of the expected value. Two cases of bronchial carcinoma were found in workers, both of whom were 37 years old, whereas 0.07 were expected for persons aged 35 to 39 years. Three reports suggest an association between exposure to dichloroethylenes and birth defects. However, all of these situations involved exposure to multiple contaminants, so a cause-and-effect relationship between the reported birth defects and exposure to 1,1-DCE cannot be established. Hepatotoxicity has been observed in humans after repeated exposure to 1,1-DCE, presumably by the inhalation route. ANIMAL STUDIES: One study shows no evidence that 1,1-DCE causes skin sensitization. Following high-dose exposure by the oral or inhalation route, the target organs in experimental animals are the liver, the kidney, and the Clara cells of the lung. Following low-dose, long-term exposure, the liver is the major target organ in rats following oral or inhalation exposure, but the kidney is the major target organ in mice following inhalation exposure. Bioassays for cancer by the oral route of exposure have been conducted in rats, mice, and trout. Although these bioassays have protocol limitations, none provides any significant evidence that 1,1-DCE is a carcinogen by the oral route of exposure. Bioassays for cancer by the inhalation route of exposure have been conducted in rats, mice, and hamsters. One bioassay in male mice showed an increase in the incidence of kidney adenocarcinomas at one exposure level. There is evidence that the induction of kidney adenocarcinomas is a sex- and species-specific response related to the expression of CYP2E1 in the kidney of male mice. 1,1-DCE causes gene mutations in microorganisms in the presence of metabolic activation. Most tests with mammalian cells in vitro or in vivo show no evidence of genotoxicity. No reproductive or developmental toxicity was observed at an oral exposure that caused minimal toxicity in the liver of the dams. An increased incidence of total cardiac malformations of 12-13% was recorded in pups from rats imbibing water containing either 0.15 ppm or 110 ppm 1,1-DCE over a period of 2 months prior to and subsequently the whole pregnancy period (controls had a 3% incidence of similar cardiac anomalie). An increased incidence of cardiac terata was also reported when utilizing method of continuous infusion of the chemical directly into the gravid rat uterus via implanted osmotic pumps. 1,1-DCE was a cardiac teratogen in the chick embryo, cardiac anomalies included atrial and ventricular septal defects, malformations of all valves, and great vessel abnormalities. There is evidence of fetal toxicity (delayed ossification) following inhalation exposure in the absence of maternal toxicity. The toxicity of 1,1-DCE is associated with cytochrome P450-catalyzed metabolism of 1,1-DCE to reactive intermediates that bind covalently to cellular macromolecules. The extent of binding is inversely related to loss of GSH, so that severity of tissue damage parallel the decline in GSH. Thus, the responses to 1,1-DCE at low doses with little depletion of GSH are expected to be very different from the responses at high doses causing substantial GSH depletion. ECOTOXICITY STUDIES: An 18-month carcinogenicity study of 1,1-DCE in rainbow trout (Oncorhynchus mykiss) (8 weeks old) at 4 mg/kg body weight per day was conducted. 1,1-DCE was incorporated in the feed. Tissues examined for neoplasms included liver, kidney, spleen, gill, gonads, thymus, thyroid, heart, stomach, pyloric caeca, duodenum, rectum, pancreas, and swimbladder. 1,1-DCE produced no neoplasms at the exposure levels used and no increase in liver weight. There was no evidence of any other chronic toxic effects.
1,1-Dichloroethene toxicity is caused by its reactive metabolites, which include epoxides, acyl chlorides, and halogenated aldehydes generated via oxidation by cytochrome P-450 2E1. These metabolites, especially 2,2-dichloroacetaldehyde and 2-chloroacetyl chloride, damage the liver by binding to cellular macromolecules. They also form glutathione S conjugates by the action of glutathione S-transferases located in the hepatic cytosol and microsomes. These are delivered to the kidney, where renal processing by beta-lyase and cysteine conjugate S-oxidase lead to nephrotoxic products. The metabolites are also known to damage the bronchiolar Clara cells in the lung. (L185)
Evaluation: There is inadequate evidence in humans for the carcinogenicity of vinylidene chloride. There is limited evidence in experimental animals for the carcinogenicity of vinylidene chloride. Overall evaluation: Vinylidene chloride is not classifiable as to its carcinogenicity to humans (Group 3). /To be changed to Group 2B (Possibly carcinogenic to humans) in a volume still in progress/
Under the 1986 cancer guidelines (U.S. EPA, 1986), 1,1-DCE is assigned to Group C, possible human carcinogen. Under the draft revised guidelines for carcinogen risk assessment (U.S. EPA, 1999), EPA concludes 1,1-DCE exhibits suggestive evidence of carcinogenicity but not sufficient evidence to assess human carcinogenic potential following inhalation exposure in studies in rodents. Male mice developed kidney tumors at one exposure in a lifetime bioassay, a finding tempered by the absence of similar results in female mice or male or female rats and by the enzymatic differences (i.e., CYP2E1) between male mice and female mice, male and female rats, and human kidney cells. Limited evidence of genotoxicity has been reported in bacterial systems with metabolic activation. The data for 1,1-DCE are inadequate for an assessment of human carcinogenic potential by the oral route, based on the absence of statistically or biologically significant tumors in limited bioassays in rats and mice balanced against the suggestive evidence in male mice in a single bioassay by inhalation and the limited evidence of genotoxicity. The human epidemiological results on the carcinogenicity of 1,1-DCE are too limited to draw useful conclusions. EPA concludes that the results of kidney tumors in one sex and one exposure in a single species of rodents are too limited to support an exposure-response assessment.
1,1-DCE is rapidly absorbed following inhalation and oral exposures. Because of its low molecular weight and hydrophobic nature, dermal absorption is also likely ... . In rats treated with 1,1-DCE by gavage in corn oil, complete gastrointestinal absorption was found to occur at <350 mg/kg. 1,1-DCE is easily transported across the alveolar membrane. ... The major route of excretion for unchanged 1,1-DCE is through the lung. However, the majority of 1,1-DCE is rapidly metabolized to nonvolatile compounds and covalently bound derivatives. Mice metabolize more 1,1-DCE than do rats. For example, when given 50 mg/kg by oral gavage in corn oil, mice excreted 6% and rats excreted 28% of the dose as unchanged 1,1-DCE through the lungs. When exposed to 10 ppm for a single 6-hour episode, mice excreted 0.65% and rats excreted 1.63% of the absorbed dose as unchanged 1,1-DCE through the lungs. Intraperitoneal administration of 125 mg/kg (14)C-1,1-DCE to mice resulted in the highest concentrations of covalent binding (based on protein content) in the kidney, lung, and liver. The covalent binding and cellular damage in kidney, lung, and liver correlated with the high concentration of CYP2E1 in certain cell populations in these tissues.
The objective of this investigation was to elucidate the effects of route of exposure and oral dosage regimen on the toxicokinetics (TK) of 1,1-dichloroethylene (DCE). Fasted male Sprague-Dawley rats that inhaled 100 or 300 ppm for 2 hr absorbed total systemic doses of (10 or 30 mg/kg DCE, respectively. Other groups of rats received 10 or 30 mg/kg DCE by intravenous injection, bolus gavage (by mouth), or gastric infusion (g.i.) over a 2-hr period. Serial microblood samples were taken from the cannulated, unanesthetized animals and analyzed for DCE content by gas chromatography to obtain concentration versus time profiles. Inhalation resulted in substantially higher peak blood concentrations and area under blood-concentration time curves (AUC(0)(2)) than did gastric infusion of the same dose over the same time frame at each dosage level, although inhalation (AUC(0)(infinity)) values were only modestly higher. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase (GGT) activities were monitored as indices of kidney injury in the high-dose groups. NAG and GGT excretion were much more pronounced after inhalation than gastric infusion. Administration of DCE by gavage also produced much higher Cmax and AUC(0)(2) values than did 2-hr g.i., although AUC(0)(infinity) values were not very different. The 30 mg/kg bolus dose produced marked elevation in serum sorbitol dehydrogenase, an index of hepatocellular injury. Administration of this dose by inhalation and gastric infusion was only marginally hepatotoxic. These findings demonstrate the TK and target organ toxicity of DCE vary substantially between different exposure routes, as well as dosage regimens, making direct extrapolations untenable in health risk assessments.
As dose level of radioactive vinylidene chloride is incr in rats from 1-50 mg/kg body wt orally, or from 40-800 mg/cu m (10-200 ppm) by inhalation, the metabolic pathway becomes saturated, so that smaller percentage of dose admin is metabolized & more is eliminated via lung as vinylidene chloride. With the 1 mg/kg body wt oral dose & the 10 ppm inhalation dose, there was no difference in elimination by fed versus fasted rats. At 50 mg/kg body wt orally or 200 ppm by inhalation, there was significant incr in excretion of vinylidene chloride via lung & decr in urinary excretion of radioactivity in fed versus fasted rats. The main excretory route for (14)C-vinylidene chloride after intragastric, iv, or ip admin to rats is pulmonary: both unchanged vinylidene chloride & related carbon dioxide are excreted by that route; other VDC metabolites are eliminated via kidneys.
/In rats/ seventy-two hr after dose of 0.5, 5.0 and 50.0 mg/kg, 1.26, 9.70, 16.47% respectively, are exhaled as unchanged vinylidene chloride, and 13.64, 11.35, 6.13% as (14)C-carbon dioxide. Main pathway of elimination is through renal excretion with 43.55, 53.88, 42.11% of the admin radioactivity. Through the biliary system, 15.74, 14.54, 7.65% of the activity are eliminated.
Pathways of Chlorinated Ethylene and Chlorinated Acetylene Reaction with Zn(0)
摘要：
To successfully design treatment systems relying on reactions of chlorocarbons with zero-valent metals, information is needed concerning the kinetics and pathways through which transformations occur. In this study, pathways of chlorinated ethylene reaction with Zn(0) have been elucidated through batch experiments. Data for parent compound disappearance and product appearance were fit to pseudo-first-order rate expressions in order to develop a complete kinetic model. Results indicate that reductive beta-elimination plays an important role, accounting for 15% of tetrachloroethylene (PCE), 30% of trichloroethylene (TCE), 85% of cis-dichloroethylene (cis-DCE), and 95% of trans-dichloroethylene (trans-DCE) reaction. The fraction of PCE, TCE, trans-DCE, and cis-DCE transformation that occurs via reductive elimination increases as the two-electron reduction potential (E-2)for this reaction becomes more favorable relative to hydrogenolysis. In the case of PCE a nd TCE, reductive elimination gives rise to chlorinated acetylenes. Chloroacetylene and dichloroacetylene were synthesized and found to react rapidly with zinc, displaying products consistent with both hydrogenolysis and reduction of the triple bond. Surface area-normalized rate constants (k(SA)) for chlorinated ethylene disappearance correlate well with both one-electron (E-1) and two-electron (E-2) reduction potentials for the appropriate reactions. Correlation with E-2 allows prediction of the distribution of reaction products as well as the rate of disappearance of the parent compound.
Synthesis of poly-functionalized pyrazoles under Vilsmeier-Haack reaction conditions
作者：Aleksandr V. Popov、Valentina A. Kobelevskaya、Ludmila I. Larina、Igor B. Rozentsveig
DOI：10.24820/ark.5550190.p010.934
日期：——
Synthesis of 1,3-disubstituted 5-chloro-1H-pyrazole-4-carbaldehydes was achieved by formylation of the corresponding 5-chloro-1H-pyrazoles under Vilsmeier-Haack conditions.
PREPARATION METHOD AND USE OF COMPOUNDS HAVING HIGH INSECTICIDAL ACTIVITIES
申请人：Li Zhong
公开号：US20090111847A1
公开（公告）日：2009-04-30
The present invention discloses a kind of nitromethylene derivatives as well as their preparation method and their uses. The insecticidal activity tests show that the nitromethylene derivatives of the present invention not only show high insecticidal activities against insects with piercing-sucking type or scratching type mouthparts, such as aphid, leafhopper, plant hopper, thrips and white fly and their resistant strains, but also show high insecticidal activities against
Lissorhoptrus oryzophilus
, carmine spider mite, and they can also be used to prevent sanitary pest, and white ant.
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
1,4,2-dithiazolidine or 1,3-thiazetidine heterocycles was developed by reactions of phenylthioureas with 1,1-dichloro-2-nitroethene. The solvent has a significant influence on the type of product formation. 1,4,2-Dithiazolidines were formed in the aprotic solvent chloroform, while in the protic solvent ethanol, 1,3-thiazetidines were the main products.
The preparation of 13-methylgon-4-enes and novel 13-polycarbonalkylgon-4-enes by a new total synthesis is described. 13-Alkylgon-4-enes having progestational, anabolic and androgenic activities are prepared by forming a tetracylic gonane structure unsaturated in the 1,3,5(10),9(11) and 14-positions, selectively reducing in the B- and C-rings, and converting the aromatic A-ring compounds so-produced to gon-4-enes by Birch reduction and hydrolysis.
