It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EXHO), which in turn is metabolized to 2-ethylhexanoic acid (2-EXHA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of geatation. On an equimolar basis DEHP was least potent, 2-ethylhexanol was intermediate, and 2-ethylhexanoic acid was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2-ethylhexanoic acid as the proximate teratogen.
来源:Hazardous Substances Data Bank (HSDB)
代谢
当管理员通过静脉注射或口服给药时，它会迅速代谢为单-(2-乙基己基)-邻苯二甲酸酯的衍生物。...
When admin either iv or orally, it is rapidly metabolized to derivatives of mono-(2-ethylhexyl)-phthalate. ...
Rats have been reported to metabolize di(2-ethylhexyl) phthalate to 5-keto-2-ethylhexyl phthalate, 5-carboxyl-2-ethylpentyl phthalate, 5-hydroxy-2-ethylhexyl phthalate & 2-carboxymethylbutyl phthalate after initial hydrolysis to mono(2-ethylhexyl) phthalate.
African green monkeys & ferrets, in contrast to rats, excrete di(2-ethylhexyl) phthalate metabolites in urine as glucuronide derivatives of mono(2-ethylhexyl) phthalate. Glucuronidation appears to occur at the free carboxyl group, while 2-ethylhexyl substituent is oxidized to an alcohol.
DEHP is mainly absorbed via ingestion. It is hydrolyzed in the small intestine and absorbed as monoethylhexylphthalate (MEHP) and 2-ethylhexanol, then likely distributed to the adipose tissues and kidneys. MEHP is further metabolized via numerous oxidative reactions, resulting in the formation of 30 or more metabolites, some of which can be conjugated with glucuronic acid for excretion. Oxidation of 2-ethylhexanol primarily yields 2-ethylhexanoic acid and several keto acid derivatives. Most DEHP metabolites are excreted in the urine as glucuronide conjugates, while unmetabolized DEHP is excreted in the faeces. (L181)
IDENTIFICATION AND USE: Di(2-ethylhexyl)phthalate (DEHP) is a colorless, oily liquid. Plastics may contain from 1 to 40% DEHP by weight and are used in consumer products such as imitation leather, rainwear, footwear, upholstery, flooring, wire and cable, tablecloths, shower curtains, food packaging materials and children's toys. DEHP is also used as a hydraulic fluid and as a dielectric fluid (a non-conductor of electric current) in electrical capacitors, a detector for leaks in respirators. DEHP 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: DEHP has been found in various types of food, such as fish, shellfish, eggs and cheese. Blood transfusions and other medical treatment using plastic devices may lead to involuntary human exposure to DEHP. Available data on oral administration indicate that DEHP is hydrolyzed in the gut by pancreatic lipase. The metabolites formed, i.e., mono(2-ethylhexyl)phthalate and 2-ethyl hexanol, are rapidly absorbed. Mono-2-ethylhexyl phthalate was detected in human teeth. When administered orally, DEHP is extensively hydrolyzed in the gut in certain animals, e.g., rats, and is mainly distributed as monoethylhexyl phthalate. However, hydrolysis occurs to a much lesser extent in primates and humans. Several further metabolites have been identified, omega- and omega-1-oxidation being the major metabolic pathways. DEHP metabolism shows considerable species differences, e.g., the omega-oxidation pathway is less extensive in humans than in rats. Bile and urine are the major excretory pathways. DEHP metabolites do not produce peroxisome proliferation in cultured human hepatocytes. Only very limited information is available on the effects of DEHP on humans. Mild gastric disturbances, but no other deleterious effects, were reported for two subjects. Adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity. Thyroid, liver, renal, and male and female gonadal functions tested were within normal range for age and sex distribution. ANIMAL STUDIES: Hepatomegaly and increased relative kidney weights have been observed in treated animals in long term studies, also hypertrophic cells in the anterior pituitary. Several studies have shown testicular atrophy. Younger rats seem to be more susceptible than older ones, and rats and mice seem to be more sensitive than marmosets and hamsters. Reversibility of the atrophy has been observed. DEHP, as well as monoethylhexyl phthalate, shows teratogenic properties. Tests for mutagenicity and related end points have been negative in most studies. DEHP may induce cellular transformation, and it has been shown to be carcinogenic in rats and in mice. There was a dose-related increase in hepatocellular tumors in both sexes of both species. The induction of hepatic peroxisome proliferation and cell replication is strongly associated with the liver carcinogenic effects of certain non-genotoxic carcinogens including DEHP. However, marked differences have been observed among animal species with respect to DEHP-induced peroxisome proliferation. ECOTOXICITY STUDIES: Although few relevant studies have been reported, the acute toxicity of DEHP to algae, plants, and birds appears to be low.
Monoethylhexylphthalate (MEHP), one of the major metabolites of DEHP, induces peroxisome proliferation by activating peroxisome proliferator activated receptors. This is believed to increase production of hydrogen peroxide by peroxisomes and enhance cell proliferation, leading to hepatotoxic and carcinogenic effects. MEHP is also believed to exhibit testicular toxicity by targeting and damaging the Sertoli cells. DEHP may act as an antiandrogen during a critical stage of reproductive tract differentiation by reducing testosterone in fetal males, hindering development. (L181, A106)
Classification of carcinogenicity: There is inadequate evidence in humans for the carcinogenicity of di(2-ethylhexyl) phthalate. There is sufficient evidence in experimental animals for the carcinogenicity of di(2-ethylhexyl) phthalate. Overall evaluation: Di(2-ethylhexyl) phthalate is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
邻苯二甲酸二(2-乙基己基)酯：合理预期为人类致癌物。
bis(2-Ethylhexyl) Phthalate: reasonably anticipated to be a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：B2组可能的人类致癌物
Cancer Classification: Group B2 Probable Human Carcinogen
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
当通过静脉注射或口服给药时，它主要在尿液和胆汁中排泄。
When administered either IV or orally ... it is mainly excreted in urine and bile.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
似乎血液中的物质被迅速清除，大部分在透析完成后的5-7小时内被移除。
It appeared to be rapidly cleared from blood, most being removed within 5-7 hr of completion of dialysis.
In one study of subjects who received hemodialysis, blood transfusions or blood that had previously been in contact with polyvinyl chloride medical products, di(2-ethylhexyl) phthalate was found at the following levels (ug/g wet tissue): brain (1.9), heart (0.5), kidney (1.2-2.2), liver (1.5-4.6), lung (1.4-2.2) & spleen (2.2-4.7).
The levels of di(2-ethylhexyl) phthalate in neonatal heart tissue from infants who had undergone umbilical catheterization, either alone or with admin of blood products, were reported to be higher than those in similar tissue from untreated infants.
alkaline earth salt of/the/ methylsulfuric acid 生成 邻苯二甲酸二辛酯
参考文献：
名称：
Complete Study of the Pyrolysis and Gasification of Scrap Tires in a Pilot Plant Reactor
摘要：
The pyrolysis and gasification of tires was studied in a pilot plant reactor provided with a system for condensation of semivolatile matter. The study comprises experiments at 450, 750, and 1000 degreesC both in nitrogen and 10% oxygen atmospheres. Analysis of all the products obtained (gases, liquids, char, and soot) are presented. In the gas phase only methane and benzene yields increase with temperature until 1000 degreesC. In the liquids the main components are styrene, limonene, and isoprene. The solid fraction (including soot) increases with temperature. Zinc content of the char decreases with increasing temperature.
Asymmetric epoxidation of styrene derivatives by styrene monooxygenase from Pseudomonas sp. LQ26: effects of α- and β-substituents
摘要：
Recombinant Escherichia coli expressing a styrene monooxygenase, StyAB2, from Pseudomonas sp. LQ26 was applied to synthesize a range of chiral epoxides from conjugated styrene derivatives with excellent (>99%) enantioselectivity in most cases. The substrate preference was studied with a special focus on the steric effect of alpha- and beta-substituents. (C) 2011 Elsevier Ltd. All rights reserved.
[EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
申请人：CAMP4 THERAPEUTICS CORP
公开号：WO2019195789A1
公开（公告）日：2019-10-10
The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).
[EN] PROCESS FOR PREPARING CARBOXYLIC ACID ESTERS IN THE PRESENCE OF A TITANIUM-CONTAINING CATALYST<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ESTERS D'ACIDES CARBOXYLIQUES EN PRÉSENCE D'UN CATALYSEUR CONTENANT DU TITANE
申请人：SIBUR HOLDING PUBLIC JOINT STOCK CO
公开号：WO2016043616A1
公开（公告）日：2016-03-24
The present invention relates to a process for preparing carboxylic acid esters, comprising esterification of a carboxylic acid with an alcohol in the presence of a titanium-containing catalyst selected from compounds of a general formula, Tin(OR)x(OR')xOy, wherein n is an integer from 1 to 4; у is an integer from 0 to 6; x can be the same or different and is an integer from 2 to 8; R is a linear or branched C1-C18alkyl, C3-C18cycloalkyl, R' is aryl optionally comprising an electron-donor substituent; or a mixture thereof, with the proviso that if n is 1, then x is 2 and у is 0; and if n>1, then the compounds comprise at least two alkoxy groups and two aryloxy groups. The present invention also relates to a process for preparing carboxylic acid esters, wherein a compound of general formula (I) or (II), wherein q represents an integer of 1 to 4; Y is independently R or R'; or a mixture thereof, with the proviso that the compounds comprise at least two alkoxy groups and two aryloxy groups, is used as a catalyst. The claimed process allows to reduce the amount of a used catalyst and the time of the process duration, while increasing the conversion rate of initial reagents and the yield of a target product.
Process for the preparation of olmesartan medoxomil
申请人：KRKA, tovarna zdravil, d.d., Novo mesto
公开号：EP1816131A1
公开（公告）日：2007-08-08
The present invenion relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.
[EN] HEMI-AMINAL ETHERS AND THIOETHERS OF N-ALKENYL CYCLIC COMPOUNDS<br/>[FR] ÉTHERS ET THIOÉTHERS HÉMIAMINAUX DE COMPOSÉS CYCLIQUES N-ALCÉNYLIQUES
申请人：ISP INVESTMENTS INC
公开号：WO2014116560A1
公开（公告）日：2014-07-31
Described herein are hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds that may be produced through a reaction comprising: (A) at least one first reactant represented by a structure (I), wherein X is a functionalized or unfunctionalized C1-C5 alkylene group optionally having one or more heteroatoms, and each R1, R2, and R3 is independently selected from the group consisting of hydrogen and functionalized and unfunctionalized alkyl groups optionally having one or more heteroatoms, and (B) at least one second reactant having at least one hydroxyl moiety or thiol moiety. The hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds may comprise a polymerizable moiety, in which case they may be left as-is or used to create homopolymers or non-homopolymers, or they may not comprise a polymerizable moiety. A wide variety of formulations may be created using the hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds, including personal care, oilfield, and construction formulations.
Hexahydrophthalate based compound and process for producing the same
申请人：Shieh Sung-Yueh
公开号：US20090281349A1
公开（公告）日：2009-11-12
A hexahydrophthalate based compound is adapted to use as a plasticizer that contains no phthalic acid and benzoic acid, possess physical properties superior to DEHA and DINA in transparency and adhesion and is friendly to organisms and the environment; and a process for producing the hexahydrophthalate based compound includes esterifying hexahydrophthalic anhydride, a diol, and a catalyst for decarboxylation to get hexahydrophthalic alcohol, and adding a monoacid into the hexahydrophthalic alcohol for further esterification, thereby obtaining the hexahydrophthalate based compound.
