Cis- and trans-1,1-dichloroethylene bound to the active site of hepatic microsomal cytochrome P-450 with the production of a Type I difference spectrum and stimulated CO-inhibitable hepatic microsomal NADPH oxidation. Incubation of cis- and trans-1,2-dichloroethylene plus hepatic microsomes, NADPH-generating system-EDTA resulted in the production of measurable levels of 2,2-dichloroethanol and dichloroacetaldehyde but not of 2-chloroethanol, chloroacetaldehyde or chloroacetic acid and, also, resulted in decreased levels of hepatic microsomal cytochrome P-450 and heme. In addition, dichloroacetic acid was produced from trans-dichloroethylene under these experimental conditions. The omission of any component of the incubation mixture eliminated the above effects, while the inclusion of SKF-525A, metyrapone or CO:O2 (80, v/v) diminished these effects. The effects of beta-naphthoflavone and phenobarbital pretreatment on the values of Ks, delta Amax, Km and Vmax for the binding and metabolism of the 1,2-dichloroethylenes are reported. The binding and metabolism of the 1,2-dichloroethylenes and the 1,2-dichloroethylene-mediated inactivation of cytochrome P-450 were enhanced per mg of microsomal protein, but generally not per nmole of cytochrome P-450 by prior induction with beta-naphthoflavone or phenobarbital. It is concluded that multiple forms of hepatic microsomal cytochrome P-450 bind and metabolize the 1,2-dichloroethylenes. The role of cytochrome P-450 in the metabolic activation of the dichloroethylenes is considered.
The major initial metabolites of chlorinated ethylenes in hepatocyte suspensions isolated from phenobarbital-treated rats were studied. The initial products of trans-1,2-dichloroethylene from cytochrome p450 in hepatic microsomes are rapidly and extensively metabolized in the hepatocyte, where the Phase II enzymes are present. ...
Similarities and differences have been observed in the metabolism of cis- and trans-1,2-dichloroethene. Both isomers have been shown to bind to the active site of hepatic cytochrome P-450. In addition, classic inhibitors of cytochrome P-450 have been shown to inhibit the production of dichloroacetaldehyde from both isomers. The binding and metabolism of 1,2-dichloroethene do not appear to be specific for any one form of cytochrome P-450. The cis isomer had a 4-fold greater rate of turnover in hepatic microsomes in vitro than the trans isomer. This is consistent with studies on isolated perfused rat livers, where metabolism of the cis isomer occurred at a greater rate than metabolism of the trans isomer. In addition, differences between cis- and trans-1,2-dichloroethene in the rates of formation of dichloroethanol and dichloroacetic acid have been reported in rat hepatocytes.
Metabolism of trans-1,2-dichloroethene is initially catalyzed by hepatic microsomal cytochrome P-450. This metabolism is believed to involve epoxidation of the ethylene double bond, forming dichlorinated epoxides. Dichlorinated epoxides, in turn, can undergo a non-enzymatic rearrangement. Studies on the metabolism of 1,2-dichloroethene by hepatic microsomes and hepatocytes provide evidence to suggest that dichloroacetaldehyde is the predominant metabolite of microsomal cytochrome P-450 and that it, in turn, is extensively converted to dichloroethanol and dichloroacetate by cytosolic and/or mitochondrial aldehyde and alcohol dehydrogenases present in hepatocytes. (L585)
IDENTIFICATION AND USE: trans-1,2-Dichloroethylene (trans-1,2-DCE) is a colorless, light liquid. Current uses for trans-1,2-DCE include its use as a degreasing agent and as one component of formulated products used for precision cleaning of electronic components. A small amount is used as a blowing agent for specialty foam. HUMAN STUDIES: Inhalation of high concentrations of vaporized trans-1,2-DCE depresses the central nervous system in humans. Exposure to trans-1,2-DCE at 2200 ppm caused burning of the eyes, vertigo, and nausea. ANIMAL STUDIES: Dermal effects have been shown in laboratory animals exposed dermally to trans-1,2-DCE. Application of 170 mg/kg (0.5 mL) of trans-1,2-DCE for 24 hours to clipped, intact skin of 1 female and 5 male rabbits under an occlusive wrapping produced mild or moderate erythema at all observation times (24, 48 and 72 hours). Inhalation studies were performed on both mature female rats, weighing about 180-200 g, and mature female mice, weighing about 20 g. Both animals were given either a single 8 hr exposure at 200 ppm trans-1,2-DCE or an 8 hr inhalation dose at 200 ppm over 5 consecutive days for 1 or 2 wk. Histopathological organ changes were observed after single or repetitive doses of trans-1,2-DCE at 200 ppm including slight to severe fatty degeneration of the hepatic lobules and Kupffer cells over the controls. In developmental studies in pregnant rats, marginal maternal toxicity was seen at 2000 ppm and exposures to 6000 ppm trans-1,2-DCE or caused frank maternal toxicity while the fetus was affected only at 12,000 ppm. Therefore, trans-1,2-DCE is not considered to be uniquely toxic to the rat conceptus. trans-1,2-DCE was not mutagenic in tests using Salmonella typhimurium strains in vitro without metabolic activation and in vivo with metabolic activation (host-mediated assay), or in a cytogenetic analysis of bone marrow cells from female mice after single and repeated ip applications (5/day) 6, 24 and 48 hr following the last application. trans- and cis-1,2-DCE isomers inhibit their own metabolism in vivo by inactivation of the metabolizing enzyme, presumably the cytochrome P450 isoform, CYP2E1. trans-1,2-DCE was a more potent inhibitor of CYP2E1 than cis-DCE based on both in vivo and in vitro studies.
Trans-1,2-dichloroethene is a volatile, lipophilic molecule that easily moves through the respiratory and gastrointestinal systems. It has a high affinity for lipids and blood, but little accumulation in tissues. 1,2-Dichloroethene isomers inhibit liver enzymes involved in metabolism and may increase the “toxic” response to other chemicals. Reactive metabolites of trans-1,2-dichloroethene modify the heme moiety of hepatic microsomal cytochrome P-450, resulting in a loss of both cytochrome P-450 and heme. Trans-1,2-dichloroethene can also mixed-function oxidase activities. Metabolism of trans-1,2-dichloroethene can lead to dose-related decrease in the levels of serum glutamicoxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). (L585)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
无致癌性迹象（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity (not listed by IARC). (L135)
Breathing trans-1,2-DCE can cause sever liver and kidney damages, pulmonary capillary hyperemia, as well as alveolar septal distention; depression of the central nervous sustem can occur; moderate iritis and conjunctivitis can follow eye exposure; dermatitis and irritation of mucous membranes can follow dermal exposure. Symptoms associated with lethal oral doses included decreased activity, ataxia, suppressed or total loss of righting reflex, and depressed respiration. (L585)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其蒸汽和摄入进入人体。
The substance can be absorbed into the body by inhalation of its vapour and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
吸收、分配和排泄
调查人员报告称，人类通过肺部吸收了72-75%的吸入反式-1,2-二氯乙烯。
/Investigators/ reported that 72-75% of inhaled trans-1,2-dichloroethene is absorbed through the lungs in humans.
In an experiment using isolated perfused liver from female Wistar rats, at equimolar concentrations in the perfusate (with chlorinated ethylenes added as vapors at constant rates that allowed for steady-state conditions of substrate uptake and conversion), uptake for cis-1,2-DCE was about 3 times faster than for trans-1,2-DCE.
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.
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.
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.
Pd‐Senphos Catalyzed
<i>trans</i>
‐Selective Cyanoboration of 1,3‐Enynes
作者：Yuanzhe Zhang、Bo Li、Shih‐Yuan Liu
DOI：10.1002/anie.202005882
日期：2020.9.7
The first trans‐selective cyanoboration reaction of an alkyne, specifically a 1,3‐enyne, is described. The reported palladium‐catalyzed cyanoboration of 1,3‐enynes is site‐, regio‐, and diastereoselective, and is uniquely enabled by the 1,4‐azaborine‐based Senphos ligand structure. Tetra‐substituted alkenyl nitriles are obtained providing useful boron‐dienenitrile building blocks that can be further
A Catalytic Approach for Enantioselective Synthesis of Homoallylic Alcohols Bearing a <i>Z</i>-Alkenyl Chloride or Trifluoromethyl Group. A Concise and Protecting Group-Free Synthesis of Mycothiazole
作者：Ryan J. Morrison、Farid W. van der Mei、Filippo Romiti、Amir H. Hoveyda
DOI：10.1021/jacs.9b11178
日期：2020.1.8
catalytic processes and is expected to facilitate the preparation of bioactive organic molecules. More specifically, Z-chloro-substituted allylic pinacolatoboronate is first obtained through stereoretentive cross-metathesisbetween Z-crotyl-B(pin) (pin = pinacolato) and Z-dichloroethene, both of which are commercially available. The organoboron compound may be used in the central transformation of the entire
Nickel-Phosphine Complex-Catalyzed Grignard Coupling. I. Cross-Coupling of Alkyl, Aryl, and Alkenyl Grignard Reagents with Aryl and Alkenyl Halides: General Scope and Limitations
(s)), aryl, and alkenyl Grignard reagents and nonfused, fused, and substituted aromatic halides and haloolefins. Limitations lie in sluggish reactions between alkyl Grignard reagents and dihaloethylenes. The most effective catalysts are [Ni(C6H5)2P(CH2)3P(C6H5)2}Cl2] for alkyl and simple aryl Grignard reagents, [Ni(CH3)2P(CH2)2P(CH3)2}Cl2] for alkenyl and allylic Grignard reagents and [NiP(C6H5)3}2-Cl2]
已经确定，二卤代二膦镍 (II) 配合物对格氏试剂与芳基和链烯基卤化物的选择性交叉偶联表现出极高的催化活性。由于该催化反应程序简单、反应条件温和、偶联产物的收率和纯度高，以及广泛适用于涉及伯和仲烷基的反应（无论β-的存在与否），该催化反应可用于合成实践。氢 (s))、芳基和烯基格氏试剂以及非稠合、稠合和取代的芳族卤化物和卤代烯烃。限制在于烷基格氏试剂和二卤乙烯之间的缓慢反应。对于烷基和简单的芳基格氏试剂，最有效的催化剂是 [Ni(C6H5)2P(CH2)3P(C6H5)2}Cl2]，[Ni(CH3)2P(CH2)2P(CH3)2}Cl2] 用于烯基和烯丙基格氏试剂，[NiP(C6H5)3}2-Cl2] 用于空间位阻芳基格氏试剂和卤化物。膦配体对...的巨大稳定作用
New 1,3-dithiol-2-ylidene-alkylsulfonylacetates and their uses
申请人：Hokko Chemical Industry Co., Ltd.
公开号：US04822814A1
公开（公告）日：1989-04-18
As new compound are provided alkyl 1,3-dithiol-2-ylidene-alkylsulfonylacetates which are useful as fungicidal agent and agent for therapeutically treating or preventing a liver disorder as well as agent for reducing the internal fat deposit or preventing excessive accumulation of the internal fat deposit in the body of animals, including humans. These new compounds have improved activities for these applications, as compared to known similar compounds.
