... 1,2-DICHLOROPROPANE ... IS PARTLY METABOLIZED TO CO2, /UNCHANGED/ 1,2-DICHLOROPROPANE AS WELL AS CO2 METABOLIZED 1,2-DICHLOROPROPANE ARE EXCRETED /IN EXPIRED AIR/.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在大鼠肝微粒体体外实验中，已经证明能够代谢1,2-二氯丙烷。
It has been shown that rat liver microsomes in vitro are capable of metabolizing 1,2-dichloropropane.
The metabolism of 1,2-dichloropropane and its proposed intermediate metabolite 1-chloro-2-hydroxypropane were studied. Sprague-Dawley rats received labeled dichloropropane in ip doses of 100 mg/kg, or by continuous oral dosing at 20 mg/kg per day for four days, while labeled 1-chloro-2-hydroxypropane was administered via ip injections at doses of 100 mg/kg. Urine was collected without fecal contamination for analysis via thin layer chromatography. During in vitro studies, a reaction was carried out in an oxidizing system using 1,2-dichloropropane as the substrate. ... The major urinary metabolite of 1,2-dichloropropane was N-acetyl-S-(hydroxypropyl)cysteine, with 2 minor metabolites, beta-chlorolactate and N-acetyl-S-(2,3-dihydroxypropyl)cysteine. Aside from N-acetyl-S-(2-hydroxypropyl)cysteine, a known urinary metabolite of 1-chloro-2-hydroxypropane, beta-chloroacetaldehyde and beta-chlorolactate were also identified as urinary 1-chloro-2-hydroxypropane metabolites ... /It was/ concluded that 1,2-dichloropropane oxidation to 1-chloro-2-hydroxypropane, ultimately resulting in the production of N-acetyl-S-(2-hydroxypropyl)cysteine, is suggested as the pathway of 1,2-dichloropropane metabolism in rats. The major detoxicating pathway of 1-chloro-2-hydroxypropane is epoxidation to 1,2-epoxypropane, which can either conjugate with glutathione or be hydrolyzed to propane-1,2-diol.
1,1-Dichloropropane & 1,2-dichloropropane are enzymatically dechlorinated by an enzyme located in hepatic microsomes. This system requires reduced nicotinamide adenine dinucleotide phosphate & oxygen, & is inducible by phenobarbital & benzpyrene, but not by methylcholanthrene. The optimum pH of the system is 8.2.
IDENTIFICATION: 1,2-Dichloropropane is a liquid. It is soluble in water, ethanol, and ethyl ether. When heated, it emits highly toxic fumes of phosgene. 1,2-dichloropropane is used in furniture finish, dry cleaning fluid, and paint remover, gum processing, metal degreasing, oil processing, and as a rubber- and wax-making agent, and a chemical intermediate int he production of tetrachloroethylene and carbon tetrachloride. HUMAN EXPOSURE: Exposure of the general population to 1,2-dichloropropane via air and water is unlikely, except in areas where there is extensive use of 1,2-dichloropropane and "MIX D/D" in agriculture. The risk to the general population is negligible. Several cases of acute poisoning have been reported due to accidental or intentional (suicide) over-exposure to 1,2-dichloropropane. Effects have been mainly on the central nervous system, liver, and kidneys. Hemolytic anemia and disseminated intravascular coagulation have also been reported. In one case, delirium progressed to irreversible shock, cardiac failure, and death. Occupational exposures can be via both skin and inhalation. Several cases of dermatitis and skin sensitization have been reported in workers using solvent mixtures containing 1,2-dichloropropane. ANIMAL STUDIES: The acute oral toxicity of 1,2-dichloropropane in experimental animals is low. Short-term, oral toxicity studies of 1,2-dichloropropane in mice and rats showed growth inhibition, clinical toxic signs associated with central nervous system depression, and/or increased mortality at dose levels of 250 mg/kg body weight per day or higher. Studies did not indicate any teratogenic activity of 1,2-dichloropropane at oral dose levels up to 125 mg/kg body weight in the rat and 150 mg/kg body weight in the rabbit. In a carcinogenicity study on mice administered 125 or 250 mg 1,2-dichloropropane/kg body weight by gavage, a dose-related increase in the incidence of liver adenomas was observed. 1,2-Dichloropropane administered orally to rats is rapidly eliminated. Urine is the major route of elimination. Unchanged 1,2-dichloropropane is not found in urine. Three major urinary metabolites have been identified. 1,2-Dichloropropane can also be oxidized to lactate with resultant carbon dioxide or acetyl co-enzyme A production.
Evaluation: There is sufficient evidence in humans for the carcinogenicity of 1,2-dichloropropane. 1,2-Dichloropropane causes cancer of the biliary tract (confirmed as cholangiocarcinoma) ... There is sufficient evidence in experimental animals for the carcinogenicity of 1,2-dichloropropane. Overall evaluation: 1,2-Dichloropropane is carcinogenic to humans (Group 1).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可分类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：1,2-二氯丙烷
IARC Carcinogenic Agent:1,2-Dichloropropane
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：1类：对人类致癌
IARC Carcinogenic Classes:Group 1: Carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
Rats receiving single oral doses of 1,2-dichloro(1-(14)C)propane excreted about 50% in the urine & 5% in feces in 24 hr. There was little further excretion over the next 72 hr. A total of 19% of the dose was excreted as (14)CO2 & 23% as other volatile substances. At 96 hr, 5% remained in the carcass.
Male & female Fischer 344 rats were either exposed to atmospheres of 5, 50 or 100 ppm (23, 230 or 460 mg/cu m) of singly labeled 1,2-dichloro((14)C))propane for a 6 hr period or dosed orally once with 1 or 100 mg/kg bw or on 7 consecutive days with 1 mg/kg bw. During inhalation exposure, maximum blood concns were reached after 2 hr, the values being approx 0.06, 0.9 & 4.0 ug/g blood, respectively. Once exposure stopped, 1,2-dichloropropane was rapidly eliminated from blood. Analysis of expired air provided evidence for saturation of metab, the proportion of expired 1,2-dichloro((14)C)propane increasing with dose. For both gavage & inhalation admin, the principal routes of elimination were urine (37-65%) & expired air (18-40%), most of the radioactivity being eliminated within 24 hr, irrespective of the route or sex. Tissues, feces & the cage wash accounted for <11%, about 10% & about 4% of the dose, respectively.
Groups of 5 male Wistar rats (200 g) were admin ip, 0, 10, 25, 50, 100, 250, or 500 mg 1,2-dichloropropane (97%)/kg bw in 0.5 ml corn oil for 5 days (once daily) or for 4 wk (5 days/wk). Urinary mercapturic acid excretion was monitored. A significant incr in mercapturic acid excretion was observed at all dose levels, with no further incr during the treatment: at lower doses, a return to baseline values occurred within 48 hr of the end of the treatment. Mercapturic acid excretion at the end of wk 2, 3, & 4 was significantly lower than that observed at the end of the first wk.
Flash vacuum pyrolysis over magnesium. Part 1. Pyrolysis of benzylic, other aryl/alkyl and aliphatic halides
作者：R. Alan Aitken、Philip K. G. Hodgson、John J. Morrison、Adebayo O. Oyewale
DOI：10.1039/b108663d
日期：2002.1.23
Flash vacuum pyrolysis over a bed of freshly sublimed magnesium on glass wool results in efficient coupling of benzyl halides to give the corresponding bibenzyls. Where an ortho halogen substituent is present further dehalogenation gives some dihydroanthracene and anthracene. Efficient coupling is also observed for halomethylnaphthalenes and halodiphenylmethanes while chlorotriphenylmethane gives 4,4′-bis(diphenylmethyl)biphenyl. By using α,α′-dihalo-o-xylenes, benzocyclobutenes are obtained in good yield, while the isomeric α,α′-dihalo-p-xylenes give a range of high thermal stability polymers by polymerisation of the initially formed p-xylylenes. Other haloalkylbenzenes undergo largely dehydrohalogenation where this is possible, in some cases resulting in cyclisation. Deoxygenation is also observed with haloalkyl phenyl ketones to give phenylalkynes as well as other products. With simple alkyl halides
there is efficient elimination of HCl or HBr to give alkenes. For aliphatic dihalides this also occurs to give dienes but there is also cyclisation to give cycloalkanes and dehalogenation with hydrogen atom transfer to give alkenes in some cases. For 5-bromopent-1-ene the products are those expected from a radical pathway but for 6-bromohex-1-ene they are clearly not. For 2,2-dichloropropane and 1,1-dichloropropane elimination of HCl occurs but for 1,1-dichlorobutane, -pentane and -hexane partial hydrolysis followed by elimination of HCl gives E,E-, E,Z- and Z,Z- isomers of the dialk-1-enyl ethers and fully assigned 13C NMR data are presented for these. With 6-chlorohex-1-yne and 7-chlorohept-1-yne there is cyclisation to give methylenecycloalkanes and -cycloalkynes. The behaviour of 1,2-dibromocyclohexane and 1,2-dichlorocyclooctane under these conditions is also examined. Various pieces of evidence are presented that suggest that these processes do
not involve generation of free gas-phase radicals but rather surface-adsorbed organometallic species.
MoCl5, 1a, and WCl6, 1b, activate 1,3-dioxolane at room temperature in chlorinated solvents: the compound [MoOCl3OC(H)OCH2CH2Cl}]2, 2, has been isolated from MoCl5/dioxolane. The mixed oxo-chloro species WOCl4, 1c, reacts with 1,3-dioxolane, selectively giving the coordination adduct WOCl4(κ1-C3H6O2), 3. Dimethoxymethane, CH2(OMe)2, undergoes activation including C–H bond cleavage when reacted with
determining the hydrogen-bond (HB) basicity of lindane (γ-hexachlorocyclohexane): (i) experimental Fourier transform IR measurement of a sum of individual 1:1 equilibrium constants for the formation of 1:1 4-fluorophenol-lindane hydrogen-bonded complexes in CCl4; (ii) calculation of the overall HB basicity from octanol–water partition coefficients; (iii) correlation of the HB basicity of chloroalkanes with the
Disclosed is a novel class of compounds of formula (I)
wherein V, A, Y, Z, R1, E, X and D are as defined in the specification. These compounds act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor, the compounds are suitable for treating or preventing glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.
