Perchloroethylene appears as a clear colorless volatile liquid having an ether-like odor. Noncombustible. Insoluble in water. Vapors heavier than air. Density approximately 13.5 lb / gal. Used as dry cleaning solvent, a degreasing solvent, a drying agent for metals, and in the manufacture of other chemicals.
When in contact with activated charcoal decomposes to form hexachloroethane and hexachlorobenzene at 700 °C.
粘度：
Liquid (cP): 0.932 at 15 °C; 0.839 at 25 °C; 0.657 at 50 °C; 0.534 at 75 °C. Vapor: 9900 cP at 60 °C
腐蚀性：
Corrosion of aluminum, iron, and zinc, which is negligible unless water is present, can be inhibited by the addition of stabilizers
燃烧热：
679.9 kJ/mol (constant pressure with formation of aq hydrochloric acid; 831.8 kJ/mol (constant volume at 18.7 °C) (to convert J to cal, divide by 4.184)
汽化热：
90.2 BTU/lb = 50.1 cal/g = 2.10X10+5 J/kg
表面张力：
31.74 dynes/cm at 20 °C in contact with vapor
电离电位：
9.32 eV
气味阈值：
The distinctive odor of tetrachloroethylene does not necessarily provide adequate warning. Because tetrachloroethylene quickly desensitizes olfactory responses, persons can suffer exposure to vapor concentrations in excess of TLV limits without smelling it.
折光率：
Index of refraction: 1.5053 at 20 °C/D
相对蒸发率：
Evaporation rate slower than that for trichloroethylene, about 3-1.
Despite the low overall metabolism of tetrachloroethylene compared with other chlorinated solvents, its metabolism has been studied extensively in both human volunteers and laboratory animals, using both in vivo and in vitro techniques. The studies showed that many metabolites are produced, including some known to be cytotoxic, mutagenic or both. Tetrachloroethylene metabolism can be viewed as having three pathways. The first is cytochrome P-450-mediated (CYP-mediated) oxidation. The second and third share a starting point: direct conjugation with glutathione to S-(1,2,2-trichlorovinyl)glutathione (TCVG) and then further processing to S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC). For the second pathway, beta-lyase catalyzes the formation of reactive products from TCVC. The third pathway is independent of beta-lyase: TCVC is processed further by acetylation and sulfoxidation reactions. Genotoxic and cytotoxic metabolites are formed by each of these pathways. The predominant metabolic pathway is the CYP path, followed by the beta-lyase pathway and then the beta-lyase independent pathway. The TCVC derivatives are toxicologically important but quantitatively minor metabolites.
Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. ... Seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 hr, with biological samples collected for analysis during exposure and up to 6 days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10 fold higher. Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. ...
来源:Hazardous Substances Data Bank (HSDB)
代谢
四氯乙烯通过CYP途径代谢的两个主要产物是三氯乙酰氯和草酰氯。
The two major products of tetrachloroethylene metabolism by the CYP pathway are trichloroacetyl chloride and oxalyl chloride.
The beta-lyase pathway: Tetrachloroethylene is conjugated with glutathione to S-(1,2,2-trichlorovinyl) glutathione and is later processed by gamma-glutamyl transpeptidase and aminopeptidase to S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC).
Tetrachloroethylene is readily absorbed following inhalation, oral, and dermal exposure. Once tetrachloroethylene is absorbed, its relatively high lipophilicity results in distribution to
fatty tissue. Some tetrachloroethylene is metabolized to trichloroacetic acid (TCA) by cytochrome P-450 enzymes and the glutathione-conjugation pathway, then excreted in the urine. The remaining unmetabolized tetrachloroethylene is exhaled. (L116)
IDENTIFICATION AND USE: Teterachloroethylene (PCE) is a colorless liquid. It is used in the textile industry for dry-cleaning and for processing and finishing. PCE is used in both cold cleaning and vapor degreasing of metals, it is also used as a chemical intermediate in the synthesis of fluorocarbons, and as a heat-exchange fluid. It is used as anthelmintic in veterinary medicine. HUMAN STUDIES: Potential symptoms of overexposure are irritation of eyes, nose and throat, nausea, flushing of face and neck, vertigo, dizziness, incoordination, headache, somnolence, skin erythema, and liver damage. Liver and kidney toxicity have been reported as effects of acute exposures to very high doses. In dry cleaners chronically exposed to PCE, increased levels of markers of early renal damage or dysfunction were attributed to the exposure. In children, estimated intakes of 1.6-4.8 g/kg bw have produced vomiting, gastrointestinal bleeding, shock, and even death in one case. Epidemiology studies suggest that the risk of epilepsy and certain types of cancer such as cervical cancer may be increased among adults who were exposed to PCE-contaminated drinking water exposure during gestation and early childhood. Prenatal and early childhood exposure to PCE-contaminated drinking water may be associated with long-term subclinical visual dysfunction in adulthood, particularly with respect to color discrimination. No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders. There were no significant differences in chromosome aberrations (CA) frequency between dry cleaning workers and the controls, but analysis showed a significant association of CA frequency with employment duration and frequency of exposure to PCE. The micronuclei frequency and DNA damage detected by alkaline comet assay were significantly increased in dry cleaning workers compared to the controls. ANIMAL STUDIES: In rabbits exposed by dermal application, severe erythema and edema with necrosis of the skin was noted. In a study on guinea-pigs, 1 mL (1.62 g) of undiluted PCE applied to the skin caused severe karyolisis, edema, spongiosis, and pseudoeosinophilic infiltration. Exposure of rats at higher concentrations (>1000 ppm for four 7 hr/day exposures) resulted in CNS depression, including ataxia, somnolence, and anesthesia. Effects were diminished with repeated exposures, suggesting the development of tolerance. Rats receiving 405 mg of PCE per kg bw, for 5 days/week, during 4 weeks, showed an increased relative liver weight and increased liver aniline hydroxylase activity. Differential sensitivity of mice and rats to hepatic effects of PCE is indicated in a study that administered the compound by gavage to rats and mice for 11 days at 100, 250, 500, or 1000 mg/kg/day. Centrilobular swelling was observed at all doses in mice, and increased relative liver weights were seen for doses >250 mg/kg/day. In rats, evidence of toxic effects in the liver was only apparent at the highest dose. Rats were exposed to PCE by inhalation 6 hr/day, 5 days/week for 12 months at 300 or 600 ppm, with an additional 18 months of observation. No significant increases in tumor incidence were found for males or females. Inhalation exposure of rats 8 hr/day for 27 weeks at 70, 230, or 470 ppm tetrachloroethylene resulted in no adverse effects on reproductive performance. Rats exposed to PCE at 2060 mg/cu m air on days 6-15 of pregnancy showed reduced body weight and a slightly increased number of resorptions. No teratogenic effects were found. In the same study, pups of 17 mice, exposed to 2060 mg/cu m on days 6-15 of pregnancy showed a reduced body weight. Out of 17 litters, all showed delayed ossification of skull bones, 10 litters showed an increase in the incidence of subcutaneous edema, and 4, split sternebrae. PCE did not induce chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary cells with or without metabolic activation. In Escherichia coli K12, PCE was non-mutagenic in vitro, with or without metabolic activation. ECOTOXICITY STUDIES: PCE in groundwater and in related soil gas did not appear to reduce the size of small mammal populations or impair the health of individuals. PCE was teratogenic to amphibian embryos. PCE was teratogenic to the Japanese medaka. In field studies, PCE was added to a natural pond at the initial concentrations measured at 0.44 mg/L and 1.2 mg/L. The numbers of Daphnia declined to zero within 1 day at the higher concentration and within 3.5 days at the lower concentration.
Tetrachloroethylene is believed to affect the central nervous system by altering the fatty acid pattern of brain phospholipids and amino acids, or being incorporated into brain membranes, which may alter neural conduction velocity. Tetrachloroethylene's liver toxicity is caused mainly by its metabolite, trichloroacetic acid (TCA), which induces hepatocellular peroxisomes, causing DNA damage and leading to liver cancer. It is also thought to interfere specifically with energy-dependent hepatic transport functions by inhibiting cell membrane ATPases and decreasing hepatocyte ATP levels. (L116, A63)
Evaluation: There is limited evidence in humans for the carcinogenicity of tetrachloroethylene. Positive associations have been observed for cancer of the bladder. There is sufficient evidence in experimental animals for the carcinogenicity of tetrachloroethylene. Tetrachloroethylene is probably carcinogenic to humans (Group 2A).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3：已确认的动物致癌物，对人类的相关性未知。
A3: Confirmed animal carcinogen with unknown relevance to humans.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
四氯乙烯根据实验动物研究中充分的致癌性证据，被合理预期为人类致癌物。
Tetrachloroethylene is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
The mutagenicity of tetrachloroethene (tetra) and its S conjugate, S-(1,2,2-trichlorovinyl)glutathione (TCVG) was investigated using a modified Ames preincubation assay. TCVG was a potent mutagen in presence of rat kidney particulate fractions containing high concentrations of gamma-glutamyl transpeptidase (GGT) and dipeptidases. Purified tetra was not mutagenic without exogenous metabolic activation or under conditions favoring oxidative metabolism. Preincubation of tetra with purified rat liver glutathione (GSH) S-transferases in presence of GSH and rat kidney fractions resulted in a time-dependent formation of TCVG as determined by (HPLC) analysis and in an unequivocal mutagenic response in the Ames test. Experiments with tetra in the isolated perfused rat liver demonstrated TCVG formation and its excretion with the bile; bile collected after the addition of tetra to the isolated perfused liver was unequivocally mutagenic in bacteria in the presence of kidney particulate fractions. The mutagenicity was reduced in all cases by the GGT inhibitor serine borate or the beta-lyase inhibitor aminooxyacetic acid. These results support the suggestion that cleavage of the GSH S conjugate formed from tetra by the enzymes of the mercapturic acid pathway and by beta-lyase may be involved in the nephrocarcinogenic effects of this haloalkene in rats.
This article reports on the development of a "harmonized" PBPK model for the toxicokinetics of perchloroethylene (tetrachloroethylene or perc) in mice, rats, and humans that includes both oxidation and glutathione (GSH) conjugation of perc, the internal kinetics of the oxidative metabolite trichloroacetic acid (TCA), and the urinary excretion kinetics of the GSH conjugation metabolites N-Acetylated trichlorovinyl cysteine and dichloroacetic acid. The model utilizes a wider range of in vitro and in vivo data than any previous analysis alone, with in vitro data used for initial, or "baseline," parameter estimates, and in vivo datasets separated into those used for "calibration" and those used for "evaluation." Parameter calibration utilizes a limited Bayesian analysis involving flat priors and making inferences only using posterior modes obtained via Markov chain Monte Carlo (MCMC). As expected, the major route of elimination of absorbed perc is predicted to be exhalation as parent compound, with metabolism accounting for less than 20% of intake except in the case of mice exposed orally, in which metabolism is predicted to be slightly over 50% at lower exposures. In all three species, the concentration of perc in blood, the extent of perc oxidation, and the amount of TCA production is well-estimated, with residual uncertainties of approximately 2-fold. However, the resulting range of estimates for the amount of GSH conjugation is quite wide in humans (approximately 3000-fold) and mice (approximately 60-fold). While even high-end estimates of GSH conjugation in mice are lower than estimates of oxidation, in humans the estimated rates range from much lower to much higher than rates for perc oxidation. It is unclear to what extent this range reflects uncertainty, variability, or a combination. Importantly, by separating total perc metabolism into separate oxidative and conjugative pathways, an approach also recommended in a recent National Research Council review, this analysis reconciles the disparity between those previously published PBPK models that concluded low perc metabolism in humans and those that predicted high perc metabolism in humans. In essence, both conclusions are consistent with the data if augmented with some additional qualifications: in humans, oxidative metabolism is low, while GSH conjugation metabolism may be high or low, with uncertainty and/or interindividual variability spanning three orders of magnitude. More direct data on the internal kinetics of perc GSH conjugation, such as trichlorovinyl glutathione or tricholorvinyl cysteine in blood and/or tissues, would be needed to better characterize the uncertainty and variability in GSH conjugation in humans.
Tetrachloroethylene is a volatile, lipophilic small molecule that is rapidly and extensively absorbed after inhalation and oral exposure. It can also be rapidly absorbed through the skin, but dermal absorption appears to be a less important route of exposure. In humans, inhalation exposure to tetrachloroethylene typically results, within a few hours of exposure, in a pseudoequilibrium between inspired air and blood although there can be substantial interindividual differences in absorption behavior. After oral dosing in animals, peak blood tetrachloroethylene concentrations are typically reached within 15-30 min, and systemic bioavailability is typically greater than 80%; once absorbed, tetrachloroethylene is rapidly distributed throughout the body, and well-perfused tissues reach a pseudoequilibrium with blood within a few minutes.
Because of its lipophilicity, the highest concentrations of tetrachloroethylene are found in adipose tissue. In humans, the fat-to-blood concentration ratio has been estimated to be as high as 90:1. Relatively high concentrations are also observed in the liver and brain. On the basis of animal studies and sparse human data, the brain concentration of tetrachloroethylene is 4-8 times the blood concentration.
A Fabric Denuder for Sampling Semi-Volatile Species
摘要：
A new style of diffusion denuder has been evaluated specifically for sampling HNO3. A coated fabric is used as the denuder substrate, which can be loaded directly into a standard filter holder. This approach allows direct denuder sampling with no additional capital costs over filter sampling and simplifies the coating and extraction process.Potential denuder materials and coatings were evaluated in the laboratory to test the removal efficiency. NaCl coatings were used to assess more than 20 materials for HNO3 collection efficiency. Particle retention, which would cause a denuder to have a positive bias for gas concentration measurements, was evaluated by ambient air sampling using particulate sulfate as the reference aerosol. Particle retention varied from 0 to 15%, depending on the denuder material tested. The best performing material showed an average particle retention of less than 3%.Denuder efficiency of four fabric materials was tested under ambient conditions to determine removal efficiency. The fabric denuder method was compared with a long path-length Fourier transform infrared (FTIR) spectrometer, a tunable diode laser absorption spectrometer (TDLAS), and a denuder difference sampler to independently measure HNO3. HNO3 collection efficiency was typically 90% for the denuders, whether coated with NaCl or not. For 10-L/min sampling rates with the fabric denuder, the square of the correlation coefficient with the FTIR spectrometer was 0.73, compared to 0.24 with the TDLAS.
Novel processes for the preparation of adenosine compounds and intermediates thereto
申请人：——
公开号：US20030069423A1
公开（公告）日：2003-04-10
Novel processes for the preparation of adenosine compounds and intermediates thereto. The adenosine compounds prepared by the present processes may be useful as cardiovascular agents, more particularly as antihypertensive and anti-ischemic agents, as cardioprotective agents which ameliorate ischemic injury or myocardial infarct size consequent to myocardial ischemia, and as an antilipolytic agents which reduce plasma lipid levels, serum triglyceride levels, and plasma cholesterol levels. The present processes may offer improved yields, purity, ease of preparation and/or isolation of intermediates and final product, and more industrially useful reaction conditions and workability.
[EN] SUBSTITUTED QUINAZOLINES AS FUNGICIDES<br/>[FR] QUINAZOLINES SUBSTITUÉES, UTILISÉES EN TANT QUE FONGICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2010136475A1
公开（公告）日：2010-12-02
The present invention relates to a compound of formula (I) wherein wherein the substituents have the definitions as defined in claim 1or a salt or a N-oxide thereof, their use and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
[EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF<br/>[FR] MODULATEURS DE CALPAÏNE ET LEURS UTILISATIONS THÉRAPEUTIQUES
申请人：BLADE THERAPEUTICS INC
公开号：WO2019190885A1
公开（公告）日：2019-10-03
Small molecule calpain modulator compounds, including their pharmaceutically acceptable salts, can be included in pharmaceutical compositions. The compounds can be useful in inhibiting calpain, or competitive binding with calpastatin, by contacting them with CAPN1, CAPN2, and/or CAPN9 enzymes residing inside a subject. The compounds and composition can also be administered to a subject in order to treat a fibrotic disease or a secondary disease state or condition of a fibrotic disease.
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.
式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
[EN] ANTI-CANCER AND ANTI-HIV COMPOUNDS<br/>[FR] COMPOSÉS ANTICANCÉREUX ET ANTI-VIH
申请人：SIRENAS MARINE DISCOVERY
公开号：WO2014123900A1
公开（公告）日：2014-08-14
Disclosed herein are compounds useful as anti-cancer and anti-HIV agents. Also disclosed are pharmaceutical compositions and methods of treatment. The compounds disclosed herein can be used to treat a variety of conditions, diseases and ailments such as bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, and thyroid cancer, and HIV related disorders.
