Diethyl phthalate appears as a clear, colorless liquid without significant odor. More dense than water and insoluble in water. Hence sinks in water. Primary hazard is to the environment. Spread to the environment should be immediately stopped. Easily penetrates soil, contaminates groundwater and nearby waterways. Flash point 325°F. Severely irritates eyes and mildly irritates skin. Used in the manufacture of perfumes, plastics, mosquito repellents and many other products.
Diethyl phthalate (10 or 100 mg) was administered to each of three Wistar rats by stomach intubation. Daily urine collections were analyzed for 10 days by GC-MS. For both doses, 77-78% of the administered dose was excreted in urine within 24 hr as monoester derivative (67-70% of the dose), phthalic acid (8-9% of the dose), or parent compound (0.1-0.4%), and about 85-93% was excreted within 1 week after administration.
Using in vitro preparations of rat, baboon, and human tissues, /investigators/ demonstrated that DEP was hydrolyzed to the monoester. Further hydrolysis of the monoester and its conjugation with glucuronic acid are consistent with the biotransformation pathways for related phthalates.
The first step of metabolism involves hydrolysis to a monoester derivative. This was seen in the in vitro metabolism of (14)C-diethyl phthalate (5-mmol/L solution) by hepatic and small intestine preparations from a rodent (rat), a nonrodent (ferret), and a nonhuman primate (baboon). Hepatic postmitochondrial supematant and intestinal preparations from the rat, baboon, and ferret were able to catalyze the hydrolysis of diethyl phthalate to its monoester derivative. Enzyme activity was expressed as micromoles of product formed per hour per gram of liver (umol/hour/g) or per milligram of intestinal mucosal cell protein (umol/hour/mg). Quantitative species differences were observed in the hepatic and intestinal studies. In the hepatic studies, diethyl phthalate hydrolase activity decreased in the following order: baboon (516 umol/hour/g) > rat (231 umol/hour/g) > ferret (45.9 umol/hour/g). In the intestinal preparation, diethyl phthalate hydrolase activity decreased in the same order: baboon (4.33 umol/hour/mg) > rat (0.648 umol/hour/mg) > ferret (0.053 umol/hour/mg). Studies were also performed with samples of human duodenum and jejunum tissues. As with the three animal species, human intestinal preparations were also active in the metabolism of diethyl phthalate. The results obtained with human intestinal preparations were expressed as nanomoles of product formed per hour per milligram of intestinal protein (nmol/hour/mg). In the human intestinal preparation, the diethyl phthalate hydrolase activity was 31.2-153 nmol/hour/mg in the duodenum and 129 nmol/hour/mg in the jejunum. Similarly, of the tissues from three rat and one human studied in vitro, the rat small intestine hydrolyzed the greatest amount (36.4%) of diethyl phthalate in a 16-hour period. These results show a qualitative species similarity in the hydrolytic metabolism of diethyl phthalate in humans, a rodent, a nonrodent, and a nonhuman primate.
Once formed, the monoester derivative can be further hydrolysed in vivo to phthalic acid and excreted or conjugated to glucuronide and excreted; the terminal or next-to-last carbon atom in the monoester can be oxidized to an alcohol and excreted; or the alcohol can be successively oxidized to an aldehyde, ketone, or carboxylic acid and excreted.
Diethyl phthalate is hydrolyzed to its monoester derivative by diethyl phthalate hydrolase. 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. (L1900, A2884)
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)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类：D组 不可归类为人类致癌性
Cancer Classification: Group D Not Classifiable as to Human Carcinogenicity
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Pertinent data regarding carcinogenicity were 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
致癌性证据
A4；不可归类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Absorption of diethyl phthalate and three other phthalates (dimethyl, dibutyl, and di(2-ethylhexyl)) was measured using human epidermal skin obtained from the abdominal skin of 11 cadavers (mostly females 55 years of age or older) and subcutaneous fat removed in vitro. Epidermal membranes were set up in glass diffusion cells, and their permeability to tritiated water was measured to establish the integrity of the skin. Lag time for absorption of diethyl phthalate was 6 hr, and the steady-state absorption rate was 12.8 ug/sq cm per hour.
Percutaneous absorption of diethyl phthalate was evaluated in vitro in flow-through diffusion cells using human breast skin. Neat chemical (16-21 mg/sq cm) was applied over 72 hr to the epidermal surface of the skin, which was either uncovered or covered. The absorption of diethyl phthalate through skin was 3.9% and 4.8% of the applied doses for covered and uncovered conditions, respectively. The interindividual variation was 4-fold, ranging from 1.6% (SD 1.2) (n = 3) to 8.7% (SD 3.9) (n = 6) among skin donors.
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.
(14)C-Carboxy-labelled diethyl phthalate (2850 mg/kg body weight) was administered intraperitoneally to a group of 13 pregnant rats on either day 5 or day 10 of gestation. The results showed that radioactivity in the maternal blood peaked during the first 24 hr, then diminished quickly. A similar pattern was observed in amniotic fluid and fetal tissues. The reduction in concentration of (14)C from these tissues as a function of time was found to fit a first-order excretion curve. From this model curve, the half-life was calculated to be 2.22 days for diethyl phthalate. Radioactivity from (14)C-diethyl phthalate is transmitted across the placenta from mother to fetus for at least 15 days post-injection. (14)C radioactivity was widely distributed and was detected (<1%) in maternal blood, placenta, amniotic fluid, and developing fetuses at all gestational stages investigated.
CATALYST FOR OLEFIN POLYMERIZATION AND METHOD OF PREPARATION THEREOF
申请人：Wang Licai
公开号：US20110301385A1
公开（公告）日：2011-12-08
A catalyst for olefin polymerization and method of preparing the same are disclosed.
揭示了一种烯烃聚合的催化剂及其制备方法。
Cleavage of Carboxylic Esters by Aluminum and Iodine
作者：Dayong Sang、Huaxin Yue、Yang Fu、Juan Tian
DOI：10.1021/acs.joc.1c00034
日期：2021.3.5
A one-pot procedure for deprotecting carboxylicesters under nonhydrolytic conditions is described. Typical alkyl carboxylates are readily deblocked to the carboxylic acids by the action of aluminum powder and iodine in anhydrous acetonitrile. Cleavage of lactones affords the corresponding ω-iodoalkylcarboxylic acids. Aryl acetylates undergo deacetylation with the participation of the neighboring group
[EN] SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES<br/>[FR] N-BENZAMIDES D'ARYLE SUBSTITUÉS ET COMPOSÉS LIÉS POUR TRAITEMENT DES MALADIES AMYLOÏDES ET DES SYNUCLÉINOPATHIES
申请人：PROTEOTECH INC
公开号：WO2005113489A1
公开（公告）日：2005-12-01
Substituted diaryl compounds of the Formulae (I, II, III), where the variables are as defined in the claims, and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aß amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
[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.
The present application relates to encapsulates, compositions, products comprising such encapsulates, and processes for making and using such encapsulates. Such encapsulates comprise a core comprising a perfume and a shell that encapsulates said core, such encapsulates may optionally comprise a parametric balancing agent, such shell comprising one or more azobenzene moieties.
