Triacetin has been administered iv to mongrel dogs. The majority of infused triacetin underwent intravascular hydrolysis, and the majority of the resulting acetate is oxidized. Triacetin was found to be hydrolyzed by human intestinal lipase.
Groups of female mongrel dogs to study the metabolic effects of isocaloric and hypercaloric infusions of 5% v/v aqueous triacetin. A primed, continuous infusion of 5 umol/kg (0.3 uCi/kg/min) [(13)C]-acetoacetate and 1.0 uCi/kg (0.01 uCi/kg/min) [(3)H]-glucose was continued for 6 hr. Three hours after the start of the isotope infusion, dosing with triacetin was started. Six animals were infused at a rate of 47 umol/kg/min and seven were infused at a rate of 70 umol/kg/min triacetin for 3 hr. Blood and breath samples were taken at 15 to 30-min intervals. A group of four animals was infused with 70 umol/kg/min glycerol and used as the control for the hypercaloric infusion. During isocaloric infusion of triacetin, plasma acetate and free fatty acid concentrations were significantly increased at 30 and 60 min, respectively, and remained elevated. During hypercaloric infusion, plasma acetate concentration increased progressively throughout the study, whereas the plasma free fatty acid concentration did not change. Plasma pyruvate and lactate concentrations were significantly decreased after 30 and 90 min, respectively, and throughout the study with both isocaloric and hypercaloric infusion. The plasma insulin concentrations were modestly increased during both infusions. Plasma glucose concentration was significantly decreased during isocaloric triacetin infusion; a slight but significant increase was observed with hypercaloric infusion. Glucose clearance decreased significantly in both groups during the last hour of triacetin infusion. Plasma ketone body concentrations increased significantly by 60 min, and they remained elevated with isocaloric infusion and increased progressively with hypercaloric infusion of triacetin; the increased concentrations were due to increased ketone body production. During the last hour of infusion, resting energy expenditure was significantly increased with isocaloric triacetin.
Esterases in fungi or in serum act at pH >4 to slowly release acetic acid in situ. Extent of hydrolysis is automatically limited by increased acidity and lowering of pH.
IDENTIFICATION AND USE: Triacetin, also known as glyceryl triacetate (GTA), is a colorless liquid. It is reported to function as a cosmetic biocide, plasticizer, and solvent in cosmetic formulations. Triacetin is also used as a cellulose plasticizer in the manufacture of cigarette filters, as a carrier in fungicidal compositions, and to remove carbon dioxide from natural gas. Triacetin was affirmed as a GRAS (generally recognized as safe) human food ingredient by FDA. Triacetin has been used experimentally for the treatment of Canavan disease, a fatal dysmyelinating genetic disorder associated with aspartoacylase deficiency, resulting in decreased brain acetate levels and reduced myelin lipid synthesis in the developing brain. HUMAN EXPOSURE AND TOXICITY: In humans, commercial Triacetin has caused ocular irritation but no injury. Triacetin was not an irritant or a sensitizer in a clinical maximization study, and only very mild reactions were seen in a Duhring-chamber test using a 50% dilution. In sensitive individuals, it may cause slight irritation. ANIMAL STUDIES: Triacetin is moderately toxic by intraperitoneal, subcutaneous, and intravenous routes. The symptoms of toxicity with triacetin are primarily weakness and ataxia. Animals near death exhibit severe dyspnea, muscular tremors, and occasional convulsions, usually 2-22 min after the injection. Also various degrees of hemorrhage in the lung have been observed. It does not appear to affect the liver, spleen, heart, or kidneys. In short-term feeding studies, triacetin affected weight gain. Rats that were fed diets containing 30% triacetin as a starch substitute for 3 to 4 or 12 to 13 weeks, showed relatively poor growth. Liver enlargement was observed in all animals. Triacetin was not toxic in short-term studies when administered via inhalation or parenterally or in subchronic studies when administered via feed or inhalation. Triacetin was, at most, slightly irritating to guinea pig skin. However, in one study, it caused erythema, slight edema, alopecia, and desquamation. Triacetin was not sensitizing in guinea pigs. Triacetin caused some irritation in rabbit eyes. In a study performed on dogs, it was found that intra-gastric infusion of 1.0%-2.0% triacetin delays gastric emptying by increasing proximal stomach receptive volume, temporarily inhibiting gastric antral contractions and facilitating duodenal contractions. In a study using triacetin as a method of delivering metabolizable acetate to the brain of rats suffering traumatic brain injury, it was found that triacetin administration significantly increased the levels of both NAA (N-acetylaspartate) and ATP in the injured hemisphere 4 and 6 days after injury, and also resulted in significantly improved motor performance in rats 3 days after injury. Triacetin, with and without metabolic activation, was not mutagenic in the Ames assay using Salmonella typhimurium strains TA98, TA100, TA1535, TA153 with or without activation. It was also not mutagenic in an in vivo assay using Drosophila.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
皮肤症状
Redness.
Redness.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
毒性数据
LC50 (大鼠) > 1,721 毫克/立方米/4小时
LC50 (rat) > 1,721 mg/m3/4h
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The present studies investigated the effects of intravenous administration of the short-chain triglyceride triacetin on leucine metabolism in dogs. Animals received infusions of triacetin at 1.0 x estimated resting energy expenditure (REE), hyperenergetic triacetin at 1.5 x REE, glycerol, or saline during infusion of [(1-14)C]leucine. During both triacetin infusions, plasma alpha-ketoisocaproate concentrations increased (p < 0.05). During triacetin infusion at 1.5 REE, the plasma leucine concentration decreased (p < 0.05) and leucine rate of appearance decreased by approximately 19% (p < 0.05); this was significantly greater than the changes that occurred during triacetin at 1.0 x REE and glycerol (p < 0.05). There was no difference in leucine oxidation between the dogs given triacetin at 1.0 x REE and control groups, whereas leucine oxidation decreased by 53% during triacetin infusion at 1.5 x REE (p < 0.05). Nonoxidative leucine disappearance, an indicator of protein synthesis, did not change in any of the studies.
...Triacetin is more rapidly absorbed from the gastrointestinal tract in 3 hours than the other fats tested. Triacetin has been shown to be a source of liver glycogen and when fed in amounts equal in caloric value to 15% glucose it was utilized as efficiently as was glucose.
Mongrel dogs /were used/ to determine the systemic, hindlimb, gut, hepatic, and renal uptake of acetate during infusion of a 5% v/v aqueous solution of triacetin. A primed, continuous infusion of [1-(14)C]-acetate was continued for 7 hr with 10 animals. Three hours after the start of the tracer infusion, the animals were infused with triacetin at a rate of 47 umol/kg/min for 4 hr. Blood and breath samples were taken at 15-min intervals for the last 30 min. Steady-state conditions were achieved in plasma acetate concentrations and specific activity and in expired [(14)-C02]. Plasma acetate concentrations were 1180, 935, 817, 752, and 473 umol/L /(all values approximate)/ in the aorta, renal vein, portal vein, femoral vein, and hepatic vein, respectively. The acetate turnover rate during triacetin infusion was 2214 umol/min; systemic acetate turnover accounted for 68% of triacetin-derived acetate.
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
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
[EN] SUBSTITUTED QUINAZOLINES AS FUNGICIDES<br/>[FR] QUINAZOLINES SUBSTITUÉES, UTILISÉES EN TANT QUE FONGICIDES
申请人:SYNGENTA PARTICIPATIONS AG
公开号:WO2010136475A1
公开(公告)日:2010-12-02
The present invention relates to a compound of formula (I) wherein wherein the substituents have the definitions as defined in claim 1or a salt or a N-oxide thereof, their use and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
CHIMERIC MELANOCORTIN LIGANDS AND METHODS OF USE THEREOF
申请人:REGENTS OF THE UNIVERSITY OF MINNESOTA
公开号:US20180118789A1
公开(公告)日:2018-05-03
The invention provides compounds having the general formula I:
and salts thereof, wherein the variables Pro, DPro, DPhe, Arg, Trp, X
1
, X
2
, X
3
and X
4
have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
[EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF ATHEROTHROMBOSIS<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LE TRAITEMENT DE L'ATHÉROTROMBOSE
申请人:KANDULA MAHESH
公开号:WO2013024376A1
公开(公告)日:2013-02-21
The disclosures herein provide compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for peroral administration- transdermal administration, transmucosal, syrups, topical, extended release, sustained release, or injection. Such compositions may foe used to treatment of vascular disorders or conditions such as thrombotic cerebrovascular or cardiovascular disease or its associated complications.