The major metabolitesof benzene metabolism are phenol, hydroquinone, and catechol. These metabolites are interactive and can affect the rate of each other's metabolism because they are substrates for the P-450 enzyme system. The route of exposure has little effect on the subsequent metabolism of benzene to hemotoxic metabolites.
Metabolic products in rat ... are phenol, hydroquinone, catechol, hydroxyhydroquinone, & phenylmercapturic acid. Conjugated phenols have been reported ... except for a small amt of free phenol, all the phenolic metabolites were excreted in conjugated form. When (3)H-benzene was admin to mice, (3)H2O was also recovered from urine.
Yields N-acetyl-S-phenyl-cysteine in rat. Yields benzyl alcohol in guinea pigs. ... Yields cis-1,2-dihydro-1,2-dihydroxybenzene in pseudomonas. Phenol in pseudomonas & achromobacter. Yields cis,cis-muconic acid in rabbit. /From table/
来源:Hazardous Substances Data Bank (HSDB)
代谢
在兔子里，苯的主要羟基化产物是酚，一些儿茶酚和氢醌与乙醚硫酸或葡萄糖醛酸结合的形式在尿液中被发现。
In the rabbit, the major hydroxylation product of benzene was phenol, which along with some catechol and hydroquinone, was found in the urine conjugated with ethereal sulfate or glucuronic acid.
来源:Hazardous Substances Data Bank (HSDB)
代谢
苯已知的人类代谢物包括酚。
Benzene has known human metabolites that include phenol.
IDENTIFICATION AND USE: Benzene is a clear, colorless liquid with a sweet aromatic odor. It is used mainly as a starting material in manufacturing other chemicals, including detergents, pesticides, plastics and resins, synthetic rubber, aviation fuel, pharmaceuticals, dye, explosives, PCB gasoline, flavors and perfumes, paints and coatings, nylon intermediates, photographic chemicals. HUMAN EXPOSURE AND TOXICITY: Immediate signs and symptoms of exposure to benzene: People who breathe in high levels of benzene may develop drowsiness, dizziness, rapid or irregular heartbeat, headaches, tremors, confusion unconsciousness, death. Eating foods or drinking beverages containing high levels of benzene can cause vomiting, irritation of the stomach, dizziness, sleepiness, convulsions, rapid or irregular heartbeat, death. Long-term (a year or more) exposure to benzene causes harmful effects on the bone marrow, resulting in anemia and excessive bleeding. It can also affect the immune system, increasing the chance for infection. Some women who breathed high levels of benzene for many months had irregular menstrual periods and a decrease in the size of their ovaries. Acute deaths from benzene exposure at high concentrations have been due to ventricular fibrillation caused by exertion and release of epinephrine. Benzene causes cancer in humans. A retrospective cohort study was conducted in 233 benzene factories and 83 control factories in 12 cities in China. The benzene cohort and the control cohort consisted of 28,460 benzene exposed workers and 28,257 control workers. The leukemia mortality rate was 14/100,000 person-years in the benzene cohort and 2/100,000 person-years in the control cohort. Most (76.6%) cases of benzene leukemia were of the acute type. The mortality due to benzene leukemia was high in organic synthesis plants followed by painting and rubber synthesis industries. The concentration of benzene to which patients with a leukemia were exposed ranged from 10 to 1000 mg/cu m (mostly from 50 to 500 mg/cu m). Benzene is genotoxic in humans: a significantly increased frequency of chromatid and isochromatid breaks in the cultured lymphocytes of exposed workers has been reported, as well as a significant increase of peripheral blood lymphocyte chromosomal aberrations. Metabolic activation of benzene by rat liver microsomes induced sister chromatid exchanges and cell division delays in cultured human lymphocytes. Occupational exposure to benzene may occur through inhalation and dermal contact. The general population may be exposed to benzene via inhalation of ambient air, ingestion of food and drinking water, and dermal contact with consumer products containing benzene. ANIMAL TOXICITY STUDIES: Experimental animal studies, both inhalation and oral, also support the evidence that exposure to benzene increases the risk of cancer in multiple organ systems, including the hematopoietic system, oral and nasal cavities, liver, forestomach, preputial gland, lung, ovary, and mammary gland. Rats exposed to 3,526-8,224 ppm of benzene in a closed chamber for 15 minutes exhibited an increased number of ectopic ventricular beats. In developmental study, rats exposed to 10, 50, or 500 ppm (32, 160 & 1600 mg/cu m) of benzene for 7 hr/day had low incidence of brain and skeletal defects. Rats exposed continuously to 209.7 ppm for 10 days prior to breeding showed a complete absence of pregnancy. 1/10 rats exposed to 19.8 ppm had resorbed embryos. Genotoxicity studies have demonstrated the induction of chromosomal aberrations in bone-marrow cells from mice, rats, and rabbits treated with single or multiple daily doses of benzene ranging from about 0.2 to 2.0 mL/kg per day given either sc or ip. The major metabolites of benzene are phenol, hydroquinone, and catechol. The route of exposure has little effect on the subsequent metabolism of benzene to hemotoxic metabolites. ECOTOXICITY STUDIES: Young Coho salmon mortality was 12/20 at 50 ppm after 24 hr up to 96 hr and 30/30 at 100 ppm after 24 hr in artificial seawater at 8 °C. Herring and anchovy larvae studies showed that 35-45 ppm caused delay in development of eggs and produced abnormal larvae; 10-35 ppm caused delay in development of larvae, decrease in feeding and growth, and increase in respiration. Blue crab juveniles when exposed to sublethal concentrations of benzene (0.1 or 5.0 ppm) in a static system showed an increase in the time needed to complete a molt cycle (50 days in case of benzene-exposed crab, as compared to 33 days for controls), a slower rate of growth of regenerating limb buds, and a depressed activity of ATPase in mitochrondria. Oxygen consumption by the crab decreased from exposure to 1.0 ppm benzene.
The toxic agents of benzene are its metabolites. Benzene is able increase its toxicity by inducing cytochrome P450 2E1, its main metabolic enzyme. Benzene's primary toxic effects are decreases in haematological cell counts and bone marrow cellularity. The decrease in blood cell count may be due to the binding of metabolites such as benzene oxide to the blood proteins albumin and haemoglobin. In the bone marrow, phenolic metabolites can be metabolized by bone marrow peroxidases to highly reactive semiquinone radicals and quinones that stimulate the production of reactive oxygen species. This and direct metabolite binding leads to damage to tubulin, histone proteins, and topoisomerase II. Some metabolites also exert mutagenic effects by inhibiting other DNA associated proteins, such as mitochondrial DNA polymerase and ribonucleotide reductase, as well as covalently binding to DNA itself, causing effects such as strand breakage, mitotic recombination, chromosome translocations, and aneuploidy. (L5)
Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: sufficient; Overall summary evaluation of carcinogenic risk to humans is group 1: The chemical is carcinogenic to humans. /From table/
Benzene is readily absorbed via lung, & about 40-50% is retained. ... It is taken up preferentially by fatty & nervous tissues, & about 30-50% ... is excreted unchanged via lung; a 3-phase excretion pattern is seen at ... /approx/ 0.7-1.7 hr, 3-4 hr, & 20-30 hr.
Mice treated SC with 2 mL (3)H-labeled benzene/kg contained irreversibly bound radioactivity with decreasing binding magnitude in the following organs: liver, brain, kidney, spleen, fat. Mice treated with 2 daily SC doses of 0.5 mL (3)H-benzene/kg for 1-10 days showed a radioactivity binding with liver & bone marrow residues which increased with treatment duration, except in the case of binding to bone marrow which decreased after day 6.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
当以皮下注射的方式给予小鼠时，72%的剂量会在呼出的空气中回收。
When administered to mice subcutaneously, 72% of dose is recovered in expired air.
family of practical, liquid trifluoromethylation and pentafluoroethylation reagents is described. We show how halogen bonding can be used to obtain easily handled liquid reagentsfrom gaseous CF3I and CF3CF2I. The synthetic utility of the new reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions.
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人：AMGEN INC
公开号：WO2013123444A1
公开（公告）日：2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
Anionic chiral cobalt(III) complexes as catalysts of asymmetric synthesis of cyanohydrins
作者：Yu. N. Belokon’、V. I. Maleev、I. L. Mal’fanov、T. F. Savel’eva、N. S. Ikonnikov、A. G. Bulychev、D. L. Usanov、D. A. Kataev、M. North
DOI：10.1007/s11172-006-0338-4
日期：2006.5
Chiral coordinatively saturated cobalt(III) complexes with Schiff bases of enantio-pure amino acids are formed as Λ and Δ-isomers, which are not transformed into each other under normal conditions. These complexes catalyze the formation of enantiomerically enriched cyanohydrins from aldehydes and Me3SiCN under homo-and heterogeneous catalysis.
