It can be decomposed by contact with hot surfaces and open flame, and then yield toxic fumes that are irritating and give warning of their presence. When heated to decomposition it emits highly toxic fumes of phosgene and /hydrogen chloride/.
粘度：
0.437 mPa.s at 20 °C
腐蚀性：
Liquid methylene chloride will attack some forms of plastics, rubber and coatings.
汽化热：
28.82 kJ/mol at 25 °C; 28.06 kJ/mol at boiling point
A modified version of the original physiologically based pharmacokinetic (PBPK) model by Andersen et al. (1987) has been developed and used in conjunction with previously published human kinetic data for dichloromethane (DCM) metabolism and to assess interindividual variability in the rate of oxidative metabolism. Time-course data for 13 volunteers (10 males, 3 females) exposed to one or more concentrations of DCM (50 ppm, 100 ppm, 150 ppm, or 200 ppm) for 7.5 hr were used to optimize the maximal rate of hepatic metabolism (V(maxC)) through the cytochrome P450 pathway for each individual. DCM breath and blood concentrations were used, along with carboxyhemoglobin concentrations in blood and carbon monoxide (CO) concentrations in exhaled breath, to estimate the model parameters. Significant improvements in model fit were achieved when extrahepatic oxidative metabolism of DCM was added to the model structure. The 13 individual V(maxC) values ranged from 7.1 to 23.6 mg/hr/kg0.7 and appeared to be bimodally distributed. The distribution was not sex related and may be related to differential CYP2E1 induction. A comparison of the observed variation in V(maxC) values to other estimates of variability in the rate of oxidative metabolism and human CYP2E1 activity suggest a relatively narrow range in human hepatic activity toward DCM.
Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools for calculation of internal and target organ doses of parent compound and metabolites. PBPK models, coupled with in vivo inhalation gas-uptake data, can be useful to estimate total metabolism. Previously, such an approach was used to make predictions regarding the metabolism and to make subsequent inferences of DCM's mode of action for toxicity. However, current evidence warrants re-examination of this approach. The goal of this work was to examine two different hypotheses for DCM metabolism in mice. One hypothesis describes two metabolic pathways: one involving cytochrome P450 2E1 (CYP2E1) and a second glutathione (GSH). The second metabolic hypothesis describes only one pathway mediated by CYP2E1 that includes multiple binding sites. The results of our analysis show that the in vivo gas-uptake data fit both hypotheses well and the traditional analysis of the chamber concentration data is not sufficient to distinguish between them. Gas-uptake data were re-analyzed by construction of a velocity plot as a function of increasing DCM initial concentration. The velocity (slope) analysis revealed that there are two substantially different phases in velocity, one rate for lower exposures and a different rate for higher exposures. The concept of a "metabolic switch," namely that due to conformational changes in the enzyme after one site is occupied - a different metabolic rate is seen - is also consistent with the experimental data. Our analyses raise questions concerning the importance of GSH metabolism for DCM. Recent research results also question the importance of this pathway in the toxicity of DCM. GSH-related DNA adducts were not formed after in vivo DCM exposure in mice and DCM-induced DNA damage has been detected in human lung cultures without GSH metabolism. In summary, a revised/updated metabolic hypothesis for DCM has been examined using in vivo inhalation data in mice combined with PBPK modeling that is consistent with up-to-date models of the active site for CYP2E1 and suggests that this pathway is the major metabolizing pathway for DCM metabolism.
Dichloromethane (DCM) is a hepatic and pulmonary carcinogen in mice exposed to high doses by inhalation. It has been shown previously that the incidence of liver and lung tumors does not increase in rats or hamsters exposed to the dihaloalkane under conditions similar to those that produced tumors in mice. The biological consequences of DCM exposure to humans is therefore uncertain. The carcinogenic effects of DCM in the mouse are caused by the interaction with DNA of a glutathione (GSH) conjugate that is produced by the class theta glutathione S-transferase T1-1 (GST T1-1). The species specificity is thought to be due to the greater amount of transferase activity in mouse target organs and specific nuclear localization of GST T1-1 in target cells. This paper directly compares the relative capacity and locality of DCM activation in mouse and human tissues. The results show that mouse GST T1-1 is more efficient in catalyzing the conjugation of DCM with GSH than the orthologous human enzyme. In addition, the mouse expresses higher levels of the transferase than humans in hepatic tissue. Histochemical analysis confirmed the presence of GST T1-1 in the nucleus of mouse liver cells. However, in human liver GST T1-1 was detected in bile duct epithelial cells and hepatocyte nuclei but was also present in the cytoplasm. Taking this information into account, it is unlikely that humans have a sufficiently high capacity to activate DCM for this compound to be considered to represent a carcinogenic risk.
... Biotransformation into carbon monoxide of dichloromethane ... by rat has been reported ... more recent studies of human exposure to dichloromethane in factory workers have confirmed these findings & have also demonstrated that incr expiration of carbon monoxide also occurs.
IDENTIFICATION AND USE: Dichloromethane is a clear colorless, volatile, sweet-smelling lipophilic liquid. It is commonly used as a solvent in wood varnishes, paints, strippers, cements, vapor degreasing of metal parts. Methylene chloride is also widely used as a process solvent in the manufacture of a variety of products including food, textiles, insecticides, herbicides, steroids, antibiotics and vitamins. Not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: Methylene chloride is rapidly absorbed following inhalation, through the alveoli of the lungs into the systemic circulation. It is also absorbed from the gastrointestinal tract, and dermal exposure results in absorption but at a slower rate than via the other routes of exposure. Methylene chloride is quite rapidly excreted, mostly via the lungs in the exhaled air. It can cross the blood-brain barrier and be transferred across the placenta, and small amounts can be excreted in urine or in milk. Its biotransformation by the hepatic mixed function oxidases (MFO) leads to formation of carbon monoxide (CO) and elevated blood carboxyhemoglobin (COHb). Human exposure is mainly due to inhalation but there are incidences of toxicity from oral and dermal contact.Dermally, dichloromethane irritates the skin and eyes especially when evaporation is prevented; prolonged contact may cause chemical burns. Following inhalation of dichloromethane pulmonary edema, hearing loss, CNS depression, liver dysfunction, renal dysfunctions, cardiac stress, and effects on hematological parameters have been reported. Exposure at extremely high levels from use as a paint stripper by consumers or in an occupational setting, has been fatal. Dichloromethane is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. ANIMAL STUDIES: Dichloromethane is not teratogenic in rats or mice at concentrations up to 16,250 mg/cu m. Developmentally, dichloromethane is able to cross the placental barrier, and minor skeletal variations, fetal weight reduction, and more rapid behavioral habituation was evident in rats exposed before and during gestation. Single ip injection of dichloromethane (1330 mg/kg) into adult male rats caused renal proximal tubular degeneration. Morphological effects were observed in the cortex and the outer medulla. Prolonged exposure to high concentrations of methylene chloride (> or = 17,700 mg/cu m) caused reversible CNS effects, slight eye irritation and mortality in several laboratory species. Neurological damage was reversible in rats exposed to 7, 100 mg/cu m dichloromethane for 13 weeks via inhalation. Body weight reduction was observed in rats at 3500 mg/cu m and in mice from 17,700 m/cu m. Effects on the liver were noted in dogs continuously exposed to 3,500 mg/cu m for up to 100 days. After intermittent exposure, effects on the liver were observed in rats at 3500 mg/cu m and in mice at 14,100 mg/cu m. Other target organs are the lungs and the kidneys. Dichloromethane is considered a carcinogen. When administered at levels of 0, 60, 125, 185 and 250 mg/kg body weight/day to mice in deionized drinking water for 104 wk, the high dose male and female mice showed a transitory increase in mean leucocyte counts. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no observable effect level of 185 mg/kg body weight/day in both sexes. In a 2 year study, female rats exposed to 500, 1500, or 3500 ppm had an increase in the total number of benign mammary tumors in an exposure-related manner. This effect was also evident in male rats in the 1500- and 3500-ppm exposure groups. Male rats exposed to 1500 or 3500 ppm had an increased number of sarcomas located in or around the salivary glands. In contrast, hamsters exposed to the same concentrations had less extensive spontaneous geriatric changes, decreased mortality (females), and lacked evidence of definite target organ toxicity. Dichloromethane is mutagenic in prokaryotic microorganisms with or without metabolic activation (Salmonella or Escherichia coil). In eukaryotic systems it gives either negative or, in one case, weakly positive results.
Methylene chloride targets the lungs, blood system, and nervous system. In the lungs its metabolites damage Clara cells. It is also metabolized into carbon monoxide, which binds to hemoglobin to produce dose-dependent increases in carboxyhemoglobin. This results in the reduced oxygen transport and neurological dysfunction characteristic of carboxyhemoglobinemia (carbon monoxide poisoning). Methylene chloride is also believed to cause neurotoxicity by interfering with signal transmission in a manner similar to general anesthetics. Certain metabolites, such as formaldehyde, may result in carcinogenic effects by causing DNA single strand breaks, DNA-protein crosslinks, and other mutations. (T10, L188)
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on inadequate human data and sufficient evidence of carcinogenicity in animals; increased incidence of hepatocellular neoplasms and alveolar/bronchiolar neoplasms in male and female mice, and increased incidence of benign mammary tumors in both sexes of rats, salivary gland sarcomas in male rats and leukemia in female rats. This classification is supported by some positive genotoxicity data, although results in mammalian systems are generally negative. HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
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.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of dichloromethane. There is sufficient evidence in experimental animals for the carcinogenicity of dichloromethane. Overall evaluation: Dichloromethane is possibly carcinogenic to humans (Group 2B).
Methylene chloride is removed from the body mainly in expired air and urine. In four human subjects exposed to methylene chloride (350 mg/cu m) for 2 hr, an average of 22.6 microg methylene chloride was excreted in the urine within 24 hr after the exposure. In seven subjects exposed to 710 mg/cu m for 2 hr, the corresponding value was 81.5 ug. These data show that the amount excreted in the urine is insignificant. Methylene chloride excretion in expired air was most evident during the first 30 min after exposure. Initial post-exposure concentrations of methylene chloride in expired breath following 2-and 4-hr exposure periods were about 71 mg/cu m and fell to about 18 mg/cu m at the end of 30 min. Small amounts of methylene chloride remained in the expired air at 2.5 hr.
The fat content of the body was calculated in 12 healthy male subjects aged 21 to 35 years by means of hydrostatic weighing and anthropometric estimation of skeletal weight. The subjects were exposed to a concentration of 2,600 mg of methylene chloride per cubic meter of inspired air (750 ppm) for 1 hr while performing work at an intensity of 50 W on a bicycle ergometer. The uptake in the organism was measured continuously with the Douglas bag technique. The amount of methylene chloride absorbed correlated highly with degree of obesity and body weight. Needle biopsy specimens of subcutaneous adipose tissue were taken from the buttocks before exposure and 0, 1, 2, 3 and 4 hr after exposure. The mean yield of tissue from the 72 biopsies was 25 mg. The concentration of methylene chloride in the adipose tissue was determined by gas chromatography, using a headspace method. The mean concentration was 10.2 mg/kg 1 hr after exposure and 8.4 mg/kg after 4 hr. There was a wide distribution around the mean values. In the six slim subjects the concentration in the adipose tissue during the 4 hr after exposure was on an average twice that of the six more obese subjects. On the other hand, in spite of lower concentrations, the obese subjects had a greater calculated amount of methylene chloride in the total fat depots of the body. Two subjects were studied about 22 hr after exposure, the concentration in subcutaneous adipose tissue being 1.6 and 1.7 mg/kg, respectively, at that time.
A detailed study of the relationship between the measurements of methylene chloride in expired air or blood, carbon monoxide in expired air and CO-Hb in blood was undertaken... At the end of exposure of non-smoking, sedentary volunteers for 7.5 hr to methylene chloride vapour concentrations of 180-710 mg/cu m, the mean concentration of the solvent in alveolar air and in blood, and the percent CO-Hb saturation were measured... By 7 hr after exposure to any concentration, the expired air contained less than 3.5 mg/cu m methylene chloride; at 16 hr, only negligible levels were detected. These data suggest that, due to its rapid elimination, measurements of methylene chloride in expired air are unsuitable for use as a marker of occupational exposure.
...the effects of exercise and cigarette smoking on the uptake, metabolism and excretion of methylene chloride /was investigated/. The effects of smoking and methylene chloride exposure on CO-Hb saturation levels were found to be additive. Exercise was found to increase the absorption of methylene chloride and CO-Hb levels. However, the effects of exercise on CO-Hb were not observed to increase with heavy workloads beyond the level achieved with moderate work-loads, suggesting a saturation of this effect...
Synthesis and Anti-proliferativein-vitro Activity of Two Natural Dihydrostilbenes and their Analogues
作者：Wei-Ge Zhang、Rui Zhao、Jian Ren、Li-Xiang Ren、Jin-Guang Lin、Dai-Lin Liu、Ying-Liang Wu、Xin-Sheng Yao
DOI：10.1002/ardp.200600146
日期：2007.5
A total synthetic route for two natural dihydrostilbenes with significant cytotoxicity toward human cancer cell lines, (3‐(2‐(7‐methoxybenzo[d][1,3]dioxol‐5‐yl)ethyl)phenol 1a and 6‐(3‐hydroxyphenethyl)benzo[d][1,3]dioxol‐4‐ol 1b), which were isolated from Bulbophyllum odoratissimum Lindl, was developed via Wittig–Horner reaction. The natural products 1a and 1b were obtained in 28% and 20% overall
Interactions of “Bora-Penicilloates” with Serine β-Lactamases and DD-Peptidases
作者：Liudmila Dzhekieva、S. A. Adediran、R. F. Pratt
DOI：10.1021/bi500970f
日期：2014.10.21
intermediate/transition state analogue inhibitors of serine amidohydrolases. This group of enzymes includes bacterial β-lactamases and DD-peptidases where there has been considerable development of boronic acid inhibitors. This paper describes the synthesis, determination of the inhibitory activity, and analysis of the results from two α-(2-thiazolidinyl) boronic acids that are closer analogues of particular tetrahedral
特定的硼酸通常是丝氨酸酰胺水解酶的强力四面体中间体/过渡态类似物抑制剂。这组酶包括细菌 β-内酰胺酶和 DD-肽酶，其中硼酸抑制剂的发展相当可观。本文描述了两种 α-(2-噻唑烷基) 硼酸的合成、抑制活性的测定和结果分析，这些 α-(2-噻唑烷基) 硼酸是参与 β-内酰胺酶和 DD-肽酶催化的特定四面体中间体的更接近类似物，而不是先前描述的那些. 其中之一，2-[1-(二羟基硼烷基)(2-苯基乙酰胺基)甲基]-5,5-二甲基-1,3-噻唑烷-4-羧酸，是这些酶的脱酰四面体中间体的直接类似物。这些化合物是 C 类 β-内酰胺酶的微摩尔抑制剂，但是，非常出乎意料的是，不是 A 类 β-内酰胺酶的抑制剂。我们根据硼酸抑制 A 类酶的新机制对后一个结果进行了合理化。由于中间体在其形成途径上的不稳定性，无法获得稳定的抑制复合物。新的硼酸也不抑制细菌 DD 肽酶（青霉素结合蛋白）。该结果强烈支持先前提出的
Fungicides for the control of take-all disease of plants
申请人：Monsanto Company
公开号：US05498630A1
公开（公告）日：1996-03-12
A method of controlling Take-All disease of plants by applying a fungicide of the formula ##STR1## wherein Z1 and Z2 are C and are part of an aromatic ring which is benzothiophene; and A is selected from --C(X)-amine wherein the amine is an unsubstituted, monosubstituted or disubstituted amino radical, --C(O)--SR.sub.3, --NH--C(X)R.sub.4, and --C(.dbd.NR.sub.3)--XR.sub.7 ; B is --W.sub.m --Q(R.sub.2).sub.3 or selected from O-tolyl, 1-naphthyl, 2-naphthyl, and 9-phenanthryl, each optionally substituted with halogen or R.sub.4 ; Q is C, Si, Ge, or Sn; W is --C(R.sub.3).sub.p H.sub.(2-p) --; or when Q is C, W is selected from --C(R.sub.3).sub.p H(.sub.2-p), --N(R.sub.3).sub.m H(.sub.1-m)--, --S(O)p--, and --O--; X is 0 or S; n is 0, 1, 2, or 3; m is 0 or 1; p is 0, 1, or 2; each R and R.sub.2 is independently defined herein; R.sub.3 is C.sub.1 -C.sub.4 alkyl; R.sub.4 is C.sub.1 -C.sub.4 alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or dialkylamino; and R.sub.7 is C.sub.1 -C.sub.4 alkyl, haloalkyl, or phenyl, optionally substituted with halo, nitro, or R.sub.4 ; or an agronomic salt thereof.
Compounds and uses thereof for decreasing activity of hormone-sensitive lipase
申请人：——
公开号：US20030166644A1
公开（公告）日：2003-09-04
Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.
[EN] PENICILLIN-BINDING PROTEIN INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINE DE LIAISON À LA PÉNICILLINE
申请人：VENATORX PHARMACEUTICALS INC
公开号：WO2019226931A1
公开（公告）日：2019-11-28
Described herein are certain boron-containing compounds, compositions, preparations and their use as modulators of the transpeptidase function of bacterial penicillin-binding proteins and as antibacterial agents. In some embodiments, the compounds described herein inhibit penicillin-binding proteins. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.
