O-dichlorobenzene appears as a clear colorless liquid with a pleasant odor. Denser than water and insoluble in water. Flash point 150°F. Toxic by inhalation and ingestion. Used to make other chemicals, solvents, fumigants and insecticides and for many other uses.
颜色/状态：
Colorless liquid
气味：
Pleasant odor
蒸汽密度：
5.05 (NTP, 1992) (Relative to Air)
蒸汽压力：
1.36 mm Hg at 25 °C
亨利常数：
0.00 atm-m3/mole
大气OH速率常数：
4.20e-13 cm3/molecule*sec
自燃温度：
648 °C
分解：
When heated to decomposition it emits toxic /hydrogen/ chloride fumes.
粘度：
1.324 mPa.s at 25 °C
燃烧热：
-7969 Btu/lb= -4427 cal/g= -185.4X10+5 J/kg
汽化热：
311 J/g
表面张力：
36.61 dyn/cm
电离电位：
9.06 eV
气味阈值：
Odor of o-dichlorobenzene is detectable by avg person at 50 ppm in air. Odor becomes strong & irritation noticeable at ... concn around 100 ppm. It has fair warning properties at this level but possibility of adaptation should be recognized.
2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidneys, whereas 3,4-DCPSO2Me appeared in blood, liver, kidneys, and adipose tissue. The concentrations of 3,4-DCPSO2Me in the blood and three tissues reached maxima at 24 hr. Both aminopyrine N-demethylase and aniline hydroxylase activities and cytochrome P450 content of hepatic microsomes decreased 24 hr after administration of o-DCB. In contrast, 3,4-DCPSO2Me increased the activities of these enzymes and cytochrome P450 and b5 contents in rat liver microsomes. In both antibiotic-pretreated and bile duct-cannulated rats dosed with o-DCB, the concentrations of 2,3- and 3,4-DCPSO2Mes in blood, liver, kidneys, and adipose tissue were dramatically reduced. These findings suggest that the process of formation of methylsulfonyl metabolites of o-DCB involves biliary secretion of DCPSO2Mes and/or their precursors which will be subjected to metabolism by intestinal microflora. In antibiotic-pretreated rats, the inhibitory effects of o-DCB administration on the activities of aminopyrine- and aniline-metabolizing enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were greater than those observed in the intact rats. In bile duct-cannulated rats, the decrease in aminopyrine N-demethylase activity after administration of o-DCB was greater than that observed in the intact rats. These findings suggest that the apparent inhibition of drug-metabolizing enzymes by o-DCB is the result of simultaneous contrary effects, namely, the inductive effect of 3,4-DCPSO2Me and the stronger inhibitory effect of an unknown factor(s) on drug-metabolizing enzymes.
After ingestion of o-dichlorobenzene, urine of rabbits was found to contain 2,3- and 3,4-dichlorophenol free and o-glucuronic and sulfuric acid conjugates, 3,4- and 4,5-dichlorocatechol free and as the o-glucuronide and sulfate, and 3,4-dichlorophenylmercapturic acid.
The effect of inducers and inhibitors of microsomal mixed-function oxidases on the fate of metabolism and the extent of binding of ortho- and para-dichlorobenzene to cellular constituents suggests that arene oxides (epoxide) may be precursors of the excreted metabolites...
1,2-dichlorobenzene has known human metabolites that include 2,3-dichlorophenol and 3,4-dichlorophenol.
来源:NORMAN Suspect List Exchange
毒理性
毒性总结
1,2-二氯苯已在大鼠、小鼠和人体内的毒理学数据表明，1,2-二氯苯通过口服途径被吸收。通过皮肤或吸入途径的吸收特性不佳。预计吸入是人类暴露的主要途径。毒理学数据表明，大鼠、小鼠和人体对1,2-二氯苯的代谢概况和影响相似。大鼠和小鼠的动物研究表明，1,2-二氯苯可诱导急性肝毒性效应。大鼠单次口服暴露的LD50为1516至2138毫克/千克体重。大鼠的LC100为<= 977 ppm（5.9毫克/升），持续10小时暴露。在4小时暴露期间，20只大鼠中有1只在941 ppm（5.6毫克/升）的浓度下死亡。人体内通过摄入或吸入1,2-二氯苯的急性效应包括头痛、恶心、呕吐、眩晕、不适和昏迷。大鼠和小鼠的多次口服研究（从10天到2年不等）表明，不良影响包括肝脏和肾脏重量增加以及肝毒性。从这些重复剂量研究中，非肿瘤效应的NOAEL为60毫克/千克体重，而LOAEL为120毫克/千克体重，因为雄性小鼠的肾小管再生增加。在多种微生物和哺乳动物系统中，1,2-二氯苯在体外试验中呈阴性。然而，它确实在中国仓鼠卵巢细胞中诱导了姐妹染色单体交换，并在小鼠淋巴瘤细胞中增加了突变频率，这些都是在代谢激活的条件下发生的。在多种体内哺乳动物试验中，1,2-二氯苯呈阴性，但在小鼠骨髓的两个微核试验中有一个呈阳性。在大鼠和小鼠的两年口服研究中，认为1,2-二氯苯不具有致癌性（最大剂量为120毫克/千克体重）。在大鼠的吸入两代繁殖研究中，没有观察到对生育的影响，而在对成体有毒的剂量下，哺乳期间幼崽体重减轻。成年大鼠的NOAEL和LOAEL（肾脏和肝脏效应）分别为50 ppm（0.3毫克/升）和150 ppm（0.6毫克/升）。在大鼠和兔子的发育研究中，只有在母体有毒剂量下（400 ppm，2.4毫克/升）在大鼠中观察到发育效应。尚未进行人体流行病学研究。1,2-二氯苯已在广泛的 aquatic organisms under acute exposure, although chronic data are scarce. Results for fish ranged from 96 hr LC50=1.58 mg/L for rainbow trout to 57 mg/L for fathead minnow. Both acute and chronic toxicity to aquatic invertebrates were obtained with two results showing high acute toxicity, namely EC50's of 0.78 mg/L and 0.66 mg/L to Daphnia and Ceriodaphnia respECtively. Results from exposure to algae showed EC50 values in the 1-100 mg/L range for 1,2-dichlorobenzene. Toxicity to microorganisms can be considered slight. Although the major compartment expECted to be exposed to 1,2-dichlorobenzene is the atmosphere, there are no ECotoxicity results available for organisms exposed through the gas phase. The chlorine substituents on the chemical suggest a potential for effECts on stratospheric ozone. However, the chemical is unlikely to persist long enough to escape the troposphere, although it may persist long enough to undergo long range atmospheric transport. While there are a large number of acute data covering all trophic levels, chronic data are scarce. Therefore, an assessment factor of 100 has been chosen. The result used for determining the PNEC was the lowest chronic value obtained, i.e. 21 d NOEC = 0.63 mg/L for Daphnia magna. The PNECaquatic was therefore determined to be 6.3 ug/L.
... 1,2-Dichlorobenzene has been shown to cause eye and respiratory irritation in humans at exposure levels above 100 ppm. Skin irritation has been observed following dermal application in humans and animals. 1,2-Dichlorobenzene is absorbed via the oral route. Absorption via the dermal or inhalation routes is poorly characterized. Inhalation is expected to be the major route for human exposure. The available toxicological data indicate that metabolic profiles and effects from 1,2-dichlorobenzene exposure are similar in rats, mice and humans. Animal studies with rats and mice have shown 1,2-dichlorobenzene to induce acute hepatotoxic effects. The LD50 for a single oral exposure to 1,2-dichlorobenzene for the rat ranges from 1516 to 2138 mg/kg bw. The LC100 for the rat is </= 977 ppm (5.9 mg/L) for a 10 hour exposure. During a 4 hour exposure, 1 of 20 rats died at 941 ppm (5.6 mg/L). In humans, the acute effects of 1,2-dichlorobenzene by ingestion or inhalation are reported to be headache, nausea, vomiting, vertigo, malaise and unconsciousness. Several oral studies of rats and mice ranging from 10 days to 2 years duration indicate that the adverse effects include increases in liver and kidney weights and hepatotoxicity. From these repeat dose studies, the NOAEL for non-neoplastic effects was 60 mg/kg bw, while the LOAEL was 120 mg/kg bw due to increased renal tubular regeneration in male mice. In several microbial organisms and mammalian systems, 1,2-dichlorobenzene tested negative in vitro. However, it did induce sister chromatid exchanges in Chinese Hamster ovary cells and increased mutation frequency in mouse lymphoma cells, both in the presence of metabolic activation. 1,2-dichlorobenzene was negative in several in vivo mammalian tests, except one of two micronuclei assays in mouse bone marrow was positive. In a two-year oral study in rats and mice, 1,2-dichlorobenzene was considered not to be carcinogenic (maximum dose of 120 mg/kg bw). In an inhalation 2-generation reproduction study in rats, no fertility effects were observed and reduced pup weight during lactation occurred at doses toxic to adults. The NOAEL and LOAEL (kidney and liver effects) for adult rats were 50 (0.3 mg/L) and 150 ppm (0.6 mg/L) respectively. In developmental studies in rats and rabbits, developmental effects were only seen in rats at maternally toxic doses (400 ppm, 2.4 mg/L). No human epidemiological studies have been conducted. ... 1,2-Dichlorobenzene has been tested on a wide range of aquatic organisms under acute exposure, although chronic data are scarce. Results for fish ranged from 96 hr LC50=1.58 mg/L for rainbow trout to 57 mg/L for fathead minnow. Both acute and chronic toxicity to aquatic invertebrates were obtained with two results showing high acute toxicity, namely EC50's of 0.78 mg/L and 0.66 mg/L to Daphnia and Ceriodaphnia respectively. Results from exposure to algae showed EC50 values in the 1-100 mg/L range for 1,2-dichlorobenzene. Toxicity to microorganisms can be considered slight. Although the major compartment expected to be exposed to 1,2-dichlorobenzene is the atmosphere, there are no ecotoxicity results available for organisms exposed through the gas phase. The chlorine substituents on the chemical suggest a potential for effects on stratospheric ozone. However, the chemical is unlikely to persist long enough to escape the troposphere, although it may persist long enough to undergo long range atmospheric transport. While there are a large number of acute data covering all trophic levels, chronic data are scarce. Therefore, an assessment factor of 100 has been chosen. The result used for determining the PNEC was the lowest chronic value obtained, i.e. 21 d NOEC = 0.63 mg/L for Daphnia magna. The PNECaquatic was therefore determined to be 6.3 ug/L.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of dichlorobenzenes. There is evidence suggesting a lack of carcinogenicity in experimental animals of ortho-dichlorobenzene. ... Overall evaluation: ortho-Dichlorobenzene is not classifiable as to its carcinogenicity to humans (Group 3). /Dichlorobenzenes/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：D组 不可归入人类致癌性类别
Cancer Classification: Group D Not Classifiable as to Human Carcinogenicity
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Based on no human data and evidence of both negative and positive trends for carcinogenic responses in rats and mice. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. /based on former classification system/
Urine samples collected from 8 volunteers for 36 hr after exposure to 1,2-DCB in the range of 0.03-0.3 mg/L and, in one case up to 0.54 mg/L for two 4 hr periods with a 45 min interval were analysed for the presence of isomeric dichlorophenylmercapturic acids; ethyl esters of 2,3-dichlorophenylmercapturic acid and 3,4-dichlorophenylmercapturic acid were detected in the urine, with a linear correlation found between urinary dichlorophenylmercapturic acid concentration and the level of 1,2-DCB exposure; a first-order excretion kinetic was determined for the two dichlorophenylmercapturic acids; the half lives of 3,4-dichlorophenylmercapturic acid and 2,3-dichlorophenylmercapturic acid were determined to be 5.9 +/- 1.7 hr and 5.3 +/- 3.0 hr respectively.
The dichlorobenzenes may be absorbed through the lung, gastrointestinal tract, and intact skin. Relatively low water solubility and high lipid solubility favor their penetration of most membranes by diffusion, including pulmonary and GI epithelia, the brain, hepatic parenchyma, renal tubules, and the placenta. /Dichlorobenzenes/
The relationship between the metabolism and the toxicity of ortho-dichlorobenzene was investigated by evaluating its biotransformation, tissue distribution, blood kinetics and excretion after oral administration of 5, 50 or 250 mg/kg bw to male Wistar rats. The dose of 250 mg/kg bw had been demonstrated to be toxic in previous studies. The major route of elimination of ortho-dichlorobenzene (75-85%) was via the kidneys; excretion in the feces represented 19% of the low dose and 7% of the high dose. Excretion was nearly complete within 24 hr after the low and intermediate doses and within 48 hr after the high dose. Pretreatment with phenobarbital accelerated excretion of the high dose and resulted in an overall higher proportion of urinary excretion. Biliary excretion constituted 50-60% of the dose, indicating significant enterohepatic recirculation. The highest concentrations of radiolabel after a low dose were found in fat, liver and kidney 6 hr after administration; these then declined rapidly. The maximal concentration in blood was reached 6-8 hr after administration of the low and intermediate doses and 24 hr after the high dose. ortho-Dichlorobenzene was detected in blood only during the first 2 hr after administration of 5 mg/kg bw. The major route of biotransformation was via the glutathione pathway, 60% of the urinary metabolites being mercapturic acids; the major metabolites in bile were also conjugates of glutathione. Other major metabolites in urine were the sulfate conjugates of 2,3- and 3,4- dichlorophenol. No significant differences in metabolic profiles were observed with dose. Induction with phenobarbital increased excretion of sulfate conjugates (30% in induced rats, 20% in control rats), the main one being the conjugate of 3,4-dichlorophenol. The mercapturic acids in urine and the glutathione conjugates in bile were epoxide-derived metabolites, and no quinone- or hydroquinone-derived metabolites were observed. A high dose of ortho-dichlorobenzene results in depletion of glutathione, followed by oxidative stress and possibly binding to macromolecules.
1,2-Dichlorobenzene is well absorbed via the oral route. In rats, absorption of 1,2-dichlorobenzene from the gastrointestinal tract was considered complete at doses of 5 and 50 mg/kg bw but incomplete (83% absorption) at 250 mg/kg bw. There are no quantitative data for the dermal and inhalation absorption of 1,2-dichlorobenzene in animals or absorption of the chemical via any route in humans. Studies with rats have shown that 1,2-dichlorobenzene is distributed primarily to the adipose tissue with lesser amounts detected in the kidneys, liver and plasma. 1,2-Dichlorobenzene equivalents were bound to the kidneys, liver and plasma with covalent binding accounting for a substantial proportion of bound material. In particular, ...non-specific covalent binding to the alpha2u-globulin fraction of the rat kidney /was observed/. Several studies have found that the administration of a single dose of 1,2-dichlorobenzene by either the oral, intraperitoneal or intravenous route results in high initial tissue levels of 1,2-dichlorobenzene equivalents. Peak tissue levels occur within 1 and 6 hours, depending on the method of administration, followed by rapid decline thereafter
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.
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
申请人：Vertex Pharmaceuticals Incorporated
公开号：US20150231142A1
公开（公告）日：2015-08-20
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
[EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
申请人：BASF SE
公开号：WO2014206910A1
公开（公告）日：2014-12-31
The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
The invention relates to an improved process for preparing 3-alkoxy-2-methylbenzoic acids by heating substituted naphthalenes in the presence of alkali metal hydroxides and subsequently alkylating.
