Dimethyl phthalate appears as a water-white liquid without significant odor. Denser than water and insoluble in water. Hence sinks in water. Flash point 300°F. Eye contact may produce severe irritation and direct skin contact may produce mild irritation. Used in the manufacture of a variety of products including plastics, insect repellents, safety glass, and lacquer coatings.
颜色/状态：
Pale yellow
气味：
Slight aromatic odor
蒸汽密度：
6.69 (NTP, 1992) (Relative to Air)
蒸汽压力：
3.08X10-3 mm Hg at 25 °C /from experimentally-derived coefficients/
Intestinal extracts from man, ferrets and the baboon, as well as liver extracts from the latter 2 species, break down dimethyl phthalate to the monoester.
In vitro studies on metabolism of dimethylphthalate, dibutyl phathalate, di-n-octyl phthalate ... and diethylhexyl phthalate by rat liver and kidney liver homogenates have demonstrated that the lower the molecular weight of phthalate ester the faster the rate of metabolism. Rate of degradation of esters by rat kidney homogenates was relatively slow when compared with that by liver homogenates.
Of a single dose of 120 mg dimethyl phthalate admin to rats by stomach tube, 44.6% was detected in the urine, consisting of 77.5% as the monomethyl ester with 14.4% as 0-phthalate acid and 8.1% as intact dimethyl phthalate.
... In a host-mediated mutagenesis assay, rats were injected ip with dimethyl phthalate (DMP) (2 g/kg body weight); urine was collected for 24 hr, extracted, and analyzed for ... phthalic acid-containing derivatives. The extracted urine ... contained an equivalent of 1.96 mg phthalate/mL urine. More than 97% of the phthalic acid-containing derivatives present in the extracted urine consisted of the nonmutagenic metabolite of DMP, monomethyl phthalate (MMP). In vitro experiments showed that rat liver homogenates hydrolyzed 93% of carbonyl-labeled (14)C-DMP (7.7 mM) to MMP in 2 hr and bound 0.07 nmol of ((14)C)phthalate/mg liver macromolecules. By contrast, rat epidermal homogenates metabolized only 5% and bound 38-fold higher levels of carbonyl-labeled (14)C-DMP (2.66 nmol/mg of macromolecules), with no detectable binding to nucleic acids. Compared to epidermis and plasma, liver had a fivefold higher rate of DMP monoesterase activity (1240 nmol/hr/mg protein), which, when inhibited by 67%, resulted in a 4.4-fold increase in phthalate-bound hepatic macromolecules (0.31 vs. 0.07 nmol of carbonyl-labeled (14)C-DMP/mg macromolecules). In addition to MMP, formaldehyde was produced during the metabolism of DMP by liver. When ethanol was used to inhibit the oxidation of DMP-derived methanol by hepatic homogenates, there resulted a 74% reduction in the accumulation of formaldehyde and similar reductions of 71 and 73% in the binding of methyl-labeled (14)C-DMP to nucleic acids and macromolecules. (Methyl-labeled, unlike carbonyl-labeled, (14)C-DMP yields a (14)C-labeled methanol when hydrolyzed.) These results indicate that the DMP diester ... binds to epidermal and hepatic macromolecules other than nucleic acids, and that although the rapid hepatic metabolism of DMP to its monoester (MMP) and methanol affords protection against higher levels of phthalate binding as well as against DMP-induced bacterial mutagenesis, it also oxidizes DMP-derived methanol to formaldehyde, a metabolite that binds macromolecules, including nucleic acids.
Phthalate esters are first hydrolyzed to their monoester derivative. Once formed, the monoester derivative can be further hydrolyzed in vivo to phthalic acid or conjugated to glucuronide, both of which can then be excreted. The terminal or next-to-last carbon atom in the monoester can also be oxidized to an alcohol, which can be excreted as is or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and oxidative metabolites are excreted in the urine and faeces. (A2884)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
毒性总结
识别和使用：邻苯二甲酸二甲酯（DMP）是一种浅黄色或无色的油状液体（在42°F以下为固体），带有轻微的芳香气味。它被用作硝化纤维素和醋酸纤维素的增塑剂，树脂，以及固体火箭推进剂；漆；塑料；橡胶；涂料；安全玻璃；和成型粉末。以前它曾被用作马和牛身上的驱蝇剂，以及用作驱蛭剂。DMP在美国没有注册当前使用，但批准的农药用途可能会定期更改，因此必须咨询联邦、州和地方当局以获取当前批准的用途。人类暴露和毒性：在人类中，邻苯二甲酸二甲酯已引起皮肤刺激反应，并在一个人身上诱发了皮肤致敏。反复吸入蒸汽会刺激鼻子和上呼吸道。如果吞咽，DMP可能会引起胃部刺激，头晕和昏迷。在一个自杀性摄入含有邻苯二甲酸二甲酯和酮过氧化物的混合物的致命案例中，主要毒性症状是明显的食管炎，胃炎和出血。在含有0.4 mM DMP的培养液中培养18小时后，人类精子的体外死亡率降低了25%。在人类白细胞中没有诱导染色体损伤。DMP不是已知的人类致癌物。动物研究：DMP在反复应用于小鼠皮肤时会引起刺激和溃疡，但在兔子上只产生轻微的皮肤和眼睛影响。在多种动物物种中的急性口服和皮肤毒性较低。在大鼠的口服研究中表明，反复暴露可能会产生肾脏损害和对肝脏的轻微影响。在兔子上反复接触DMP时也看到了肾脏和肝脏损伤。通过吸入，在暴露于250 ppm的猫中观察到严重的粘膜刺激，而在1250 ppm时，动物表现出抑郁状态。在吸入0.7-1.8 mg/立方米的DMP（每天4小时）的小鼠中，连续吸入4个月后，观察到呼吸频率、神经系统、肝脏和肾脏的功能以及血液形态学的变化。在大鼠饲料中添加2%的邻苯二甲酸二甲酯一周后，睾丸和血清中的睾酮以及血清中的二氢睾酮显著减少。经口服或皮肤处理的鼠和鼠的后代是正常的，而当怀孕大鼠接受腹腔注射时，观察到胎儿死亡和畸形。当DMP反复应用于小鼠皮肤时，并没有增加已建立皮肤致癌物的肿瘤产量。在沙门氏菌typhimurium（Ames试验）中观察到诱变活性。在反复皮肤应用DMP的大鼠肝细胞中似乎有染色体损伤的证据，但在单次注射处理的小鼠骨髓细胞中没有。在培养的中国仓鼠卵巢细胞中，DMP仅在代谢激活的条件下诱导姐妹染色单体交换。DMP在培养的中国仓鼠卵巢细胞中，无论有无代谢激活，都没有诱导染色体畸变。因此，DMP仅在代谢后的某些体外研究中具有诱变性。这可能是由于形成了像甲醛这样的活性物质。由于DMP在体内不具有诱变性，任何活性代谢物似乎都能迅速解毒。生态毒性研究：100 ppm的DMP对Palaemonetes pugio（草虾）幼虫具有急性毒性。浓度为100 ppm的DMP显著增加了幼虫发育到第一个后幼虫阶段的持续时间。在蚯蚓（Eisenia fetida）暴露于两种人为污染的农业和森林土壤时，研究了包括邻苯二甲酸二甲酯在内的邻苯二甲酸酯同系物的生物有效性。在蚯蚓中没有检测到DMP。
IDENTIFICATION AND USE: Dimethyl phthalate (DMP) is a pale yellow, or colorless, oily liquid (solid below 42 °F) with slight aromatic odor. It is used as plasticizer for nitrocellulose and cellulose acetate, resins, and in solid rocket propellants; lacquers; plastics; rubber; coating agents; safety glass; and molding powders. Formerly it was used as a repellant for flies on horses and cows, and as a leech repellant. DMP is not registered for current 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: In man, dimethyl phthalate has caused skin irritation reactions and skin sensitization was induced in one individual. Repeated inhalation of the vapor irritated the nose and upper respiratory tract. If swallowed, DMP may cause irritation of the stomach, dizziness, and unconsciousness. In one fatal case of suicidal ingestion of a mixture containing dimethyl phthalate and ketone peroxides, the principal toxic symptoms were marked esophagitis, gastritis, and hemorrhage. Mortality of human sperm in vitro was reduced by 25% in cultures containing 0.4 mM DMP for 18 hr. Chromosomal damage was not induced in human white blood cells. DMP is not a known human carcinogen. ANIMAL STUDIES: DMP caused irritation and ulceration when repeatedly applied to mouse skin, but in rabbits it produced only weak skin and eye effects. Acute oral and dermal toxicity in a number of animal species was low. Oral studies in rats indicated repeated exposure may produce kidney damage and mild effects on the liver. Kidney and liver injury was seen in rabbits on repeated skin contact with DMP. By inhalation, severe mucous membrane irritation was observed in cats exposed at 250 ppm, and at 1250 ppm, animals appeared depressed. In mice inhaling 0.7-1.8 mg/cu m DMP (4 hr/day) for 4 mo, changes in the frequency of respiration, function of the nervous system, liver, and kidneys, and blood morphology were observed. Testosterone in testis and in serum and dihydrotestosterone in serum were significantly decreased in rats fed diets containing 2% dimethylphthalate for 1 week. The offspring of mice and rats treated orally or dermally were normal, whereas fetal deaths and malformations were seen when pregnant rats were given intraperitoneal injections. DMP did not enhance the tumor yield of an established skin carcinogen when applied repeatedly to the skin of mice. Mutagenic activity was observed in Salmonella typhimurium (Ames test). There was apparently some evidence of chromosome damage in the liver cells of rats given repeated skin application of DMP but not in the bone marrow cells of mice treated by single injection. In cultured Chinese hamster ovary cells, DMP induced sister-chromatid exchanges in only the presence of metabolic activation. DMP did not induce chromosomal aberrations, with or without metabolic activation, in cultured Chinese hamster ovary cells. Therefore, DMP is mutagenic only in certain in vitro studies after metabolism. This is probably due to the formation of a reactive species such as formaldehyde. Since DMP is not mutagenic in vivo, any reactive metabolites appear to be quickly detoxified. ECOTOXICITY STUDIES: 100 ppm DMP were acutely toxic to Palaemonetes pugio (grass shrimp) larvae. DMP at a concn of 100 ppm significantly increased the duration of larval development to the first postlarval stage. Bioavailability of phthalate congeners, including/ dimethyl phthalate to earthworms (Eisenia fetida) was studied when earthworms were exposed to two artificially contaminated agricultural and forest soils. DMP was not detected in earthworms.
Phthalate esters are endocrine disruptors. They decrease foetal testis testosterone production and reduce the expression of steroidogenic genes by decreasing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide 3 (insl3), an important hormone secreted by the Leydig cell necessary for development of the gubernacular ligament. Animal studies have shown that these effects disrupt reproductive development and can cause a number of malformations in affected young. (A2883)
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Pertinent data regarding carcinogenicity data was not located in the available literature. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. /Classification based on former EPA guidelines/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
Phthalate esters are endocrine disruptors. Animal studies have shown that they disrupt reproductive development and can cause a number of malformations in affected young, such as reduced anogenital distance (AGD), cryptorchidism, hypospadias, and reduced fertility. The combination of effects associated with phthalates is called 'phthalate syndrome’. (A2883)
/After/ oral admin of (14)C dimethyl phthalate to rats or mice, radioactivity was found in the blood and various tissues. Maximum values for radioactivity were observed within 1 hr. Tissue radioactivity was highest in the kidneys, followed in decreasing order by the liver, fat, and spleen. After 24 hr, 91% of the admin dose had been excreted in the urine and 4.1% in the feces.
The percutaneous absorption of a series of phthalate esters, dimethylphthalate, diethylphthalate, dibutyl phthalate, and di-(2-ethylhexyl) phthalate, was measured through human and rat epidermal membranes mounted in glass diffusion cells. The esters were applied directly to the epidermal membranes. Following application to the membranes, a lag phase followed by a linear phase of absorption was detected for each phthalate diester. Human skin was less permeable than rat skin for all four diesters. There appeared to be a trend to an increasing lag time with increasing molecular weight, but this relationship did not always hold true. The phthalate diesters were determined to have a 300 fold range of aqueous solubility and a wide range of lipophilicity. Once the diesters had contacted the human epidermal membrane, a slight increase in the permeability of the skin was detected. Relatively large changes in permeability were detected in the membrane following exposure.
This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the 14(C)phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of (14)C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of (14)C excreted in the first 24 hr decreased signficantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied (14)C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.
1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
[EN] ISOXAZOLE-THIAZOLE DERIVATIVES AS GABA A RECEPTOR INVERSE AGONISTS FOR USE IN THE TREATMENT OF COGNITIVE DISORDERS<br/>[FR] DÉRIVÉS D'ISOXAZOLE-THIAZOLE COMME AGONISTES INVERSES DU RÉCEPTEUR GABA A, UTILES DANS LE TRAITEMENT DE TROUBLES COGNITIFS
申请人：HOFFMANN LA ROCHE
公开号：WO2010127974A1
公开（公告）日：2010-11-11
The present invention is concerned with isoxazole-thiazole derivatives of formula I, having affinity and selectivity for GABA A α5 receptor, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful as cognitive enhancer or for the therapeutic and/or prophylactic treatment of cognitive disorders like Alzheimer's disease.
本发明涉及式I的异恶唑-噻唑衍生物，具有对GABA A α5受体的亲和力和选择性，其制备、含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物可用作认知增强剂或用于治疗和/或预防认知障碍，如阿尔茨海默病。
[EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2013079350A1
公开（公告）日：2013-06-06
Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.
Can Heteroarenes/Arenes Be Hydrogenated Over Catalytic Pd/C Under Ambient Conditions?
作者：Nao Tanaka、Toyonobu Usuki
DOI：10.1002/ejoc.202000695
日期：2020.9.14
Pd/C‐mediated dearomatic hydrogenation underambientconditions such as balloon pressure and room temperature can be a powerful tool for constructing alicyclic skeletons. Density functional theory calculations have been performed to confirm the mechanistic aspects and the utility of the established methodology has been demonstrated by donepezil synthesis.
[EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
申请人：UNIV EMORY
公开号：WO2013181135A1
公开（公告）日：2013-12-05
The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.
