Ethylene glycol monobutyl ether appears as a colorless liquid with a mild, pleasant odor. Less dense than water. Flash point 160°F. Irritates skin and eyes and may be toxic by ingestion. Used as a solvent and to make paints and varnish.
颜色/状态：
Colorless liquid
气味：
Mild, ether-like odor
蒸汽密度：
4.07 (NTP, 1992) (Relative to Air)
蒸汽压力：
0.88 mm Hg at 25 °C
亨利常数：
1.60e-06 atm-m3/mole
大气OH速率常数：
1.86e-11 cm3/molecule*sec
自燃温度：
238 °C (460 °F)
分解：
When heated to decomposition it emits acrid smoke and irritating fumes.
粘度：
3.15 centistokes at 25 °C
燃烧热：
-12,915 btu/lb = -7,180 cal/g = -848,000 cal/mol
汽化热：
56.59 kJ/mol at 25 °C
表面张力：
27.36 mN/m at 10 deg; 26.14 mN/m at 25 °C; 24.10 mN/m at 50 deg; 22.06 mN/m at 75 °C; 22.02 mN/m at 100 °C
In rats, EGBE is rapidly absorbed following either gavage, percutaneous administration, or inhalation exposure and is eliminated primarily in urine as 2-butoxyacetic acid (BAA) with lesser amounts of the glucuronide and sulfate conjugates of the parent alcohol. ...At low-dose levels, oxidation of the alcohol moiety to BAA via the aldehyde, mediated by alcohol dehydrogenase and aldehyde oxidase, predominated; this was saturated at a gavage dose between 125 mg/kg and 500 mg/kg. At the higher dose level, EGBE conjugation with glucuronic acid and oxidative dealkylation to form ethylene glycol became quantitatively more important. The acid, BAA, is also the primary metabolite in rats following administration of EGBE in drinking water. ...In humans, the glutamine conjugate of BAA has been reported as a urinary metabolite. No similar glycine or glutamine conjugate has been identified in rodents.
来源:Hazardous Substances Data Bank (HSDB)
代谢
乙烯醇单丁醚在大鼠肝脏中主要通过醇脱氢酶的氧化代谢。
... Ethylene glycol monobutyl ether is mainly metabolized via oxidation by alcohol dehydrogenase in the rat liver.
... the effect of alkyl group length on disposition of /2-methoxyethanol, 2-ethoxyethanol, and 2-butoxyethanol/ ... was studied in male F344/N rats allowed access for 24 hr to 2-butoxy(U-(14)C)ethanol, 2-ethoxy (U-(14)C)ethanol, or 2-methoxy(U-(14)C)ethanol in drinking water at three doses (180 to 2590 ppm), resulting in absorbed doses ranging from 100 to 1450 umols/kg body weight. The majority of the (14)C was excreted in urine or exhaled as carbon dioxide. Less than 5% of the dose was exhaled as unmetabolized glycol ether. Distinct differences in the metabolism of the glycol ethers as a function of alkyl chain length were noted. For 2-butoxyethanol 50-60% of the dose was eliminated in the urine as butoxyacetic acid and 8-10% as carbon dioxide; for 2-ethoxyethanol 25-40% was eliminated as ethoxyacetic acid and 20% as carbon dioxide; for 2-methoxyethanol 34% was eliminated as methoxyacetic acid and 10-30% as carbon dioxide. Ethylene glycol, a previously unreported metabolite of these glycol ethers, was excreted in urine, representing approximately 10, 18, and 21% of the dose for 2-butoxyethanol, 2-ethoxyethanol, and 2-methoxyethanol, respectively. Thus, for longer alkyl chain lengths, a smaller fraction of the administered glycol ether was metabolized to ethylene glycol and carbon dioxide. Formation of ethylene glycol suggests that dealkylation of the glycol ethers occurs prior to oxidation to alkoxyacetic acid and, as such, represents an alternate pathway in the metabolism of these compounds that does not involve formation of the toxic acid metabolite.
Ethylene glycol monobutyl ether was rapidly absorbed in male rats after gavage administration, metabolized, and eliminated. ... The major urinary metabolite, butoxyacetic acid, accounted for >75% of the radioactivity excreted in the urine. The 2nd major metabolite in urine was the glucuronide conjugate of ethylene glycol monobutyl ether. In the bile, the major biliary metabolite was BEG followed by butoxyacetic acid. A small quantity of the radioactivity excreted in the urine of rats treated with the low dose of ethylene glycol monobutyl ether was the sulfate conjugate of ethylene glycol monobutyl ether; however, no /butyl ethylene glycol/ was detected in the urine of rats treated with the high dose of ethylene glycol monobutyl ether. The following metabolic pathways of ethylene glycol monobutyl ether are identified: oxidation of ethylene glycol monobutyl ether to butoxyacetic acid, conjugation of ethylene glycol monobutyl ether with uridine diphosphate glucuronic acid, and conjugation of ethylene glycol monobutyl ether with the sulfate.
2-Butoxyethanol is a high production volume glycol ether. It is a colorless liquid that is miscible in water and soluble in most organic solvents. 2-Butoxyethanol is used widely as a solvent in surface coatings, such as spray lacquers, quick dry lacquers, enamels, varnishes, varnish removers and latex paint. Based on limited data, ambient exposures in air are generally in the ug/cu m range. Industrial exposure of the general population to this chemical is most likely from inhalation and dermal absorption during the use of products containing 2-butoxyethanol. Levels of airborne 2-butoxyethanol in occupational settings are typically in the mg/cu m range. The results of in vitro studies indicate that human red blood cells are not as sensitive to the hemolytic effects of 2-butoxyethanol and 2-butoxyacetic acid and also that red blood cells are more sensitive to hemolysis by 2-butoxyacetic acid than to hemolysis by 2-butoxyethanol. 2-Butoxyethanol is readily absorbed following inhalation, oral or dermal exposure. The chemical is metabolized via alcohol and aldehyde dehydrogenases, with the formation of 2-butoxyacetaldehyde and 2-butoxyacetic acid, the principal metabolite, although other metabolic pathways have also been identified. This chemical has moderate acute toxicity and it is irritating to the eyes and skin; it is not a skin sensitizer. The principal effect exerted by 2-butoxyethanol and its metabolite 2-butoxyacetic acid is hematotoxicity, with the rat being the most sensitive species. In rats, adverse effects on the central nervous system, kidneys and liver occur at higher exposure concentrations than do the hemolytic effects. In animals, adverse effects on reproduction and development have not been observed at less than toxic doses. Although the results of in vitro tests for mutagenicity of 2-butoxyethanol were inconsistent, the absence of structural alerts and the negative findings from in vivo studies indicate that 2-butoxyethanol is not mutagenic.
WEIGHT-OF-EVIDENCE CHARACTERIZATION: No reliable human epidemiological studies are available that address the potential carcinogenicity of EGBE. ... NTP /the National Toxicology Program/ reported no evidence of carcinogenic activity in male F344/N rats, and equivocal evidence of carcinogenic activity in female F344/N rats on the basis of increased combined incidences of benign and malignant pheochromocytoma (mainly benign) of the adrenal medulla. They also reported some evidence of carcinogenic activity in male B6C3F1 mice on the basis of increased incidences of hemangiosarcoma of the liver, and some evidence of carcinoma (mainly papilloma). ... because of the uncertain relevance of these tumor increases to humans, the fact that EGBE is generally negative in genotoxic tests and the lack of human data to support the findings in rodents, the human carcinogenic potential of EGBE, in accordance with the recently proposed Guidelines for Carcinogen Risk Assessment, cannot be determined at this time, but suggestive evidence exists from rodent studies. Under existing EPA guidelines, EGBE is judged to be a possible human carcinogen, Group C. There are currently no human epidemiological studies addressing the potential carcinogenicity of EGBE.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3：已确认的动物致癌物，对人类的相关性未知。
A3: Confirmed animal carcinogen with unknown relevance to humans.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of 2-butoxyethanol. There is limited evidence in experimental animals for the carcinogenicity of 2-butoxyethanol. Overall evaluation: 2-Butoxyethanol is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：2-丁氧基乙醇
IARC Carcinogenic Agent:2-Butoxyethanol
来源:International Agency for Research on Cancer (IARC)
2-Butoxyethanol (2BE) is... primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is believed to be responsible for 2BE toxicities associated with hemolysis of red blood cells. The objective of the study was to characterize the systemic disposition of 2BE and 2BAA in rats and mice during 2-yr 2BE inhalation toxicity studies. Male and female F344 rats and B6C3F1 mice (6-7 weeks old) were exposed to target 2BE concentrations of 0, 31.2, 62.5, or 125 ppm (rats), or 0, 62.5, 125, or 250 ppm (mice), by whole-body inhalation for 6 hr/day, 5 days/wk for up to 18 months. Postexposure blood samples were collected after 1 day, 2 weeks, and 3, 6, 12, and 18 months of exposure. Postexposure 16-hr urine samples were collected after 2 weeks and 3, 6, 12, and 18 months of exposure. A separate set of mice was kept in the control chamber and exposed to 2BE for 3 weeks when they were approximately 19 months old. Postexposure blood samples were collected after 1 day and 3 weeks of exposure and 16-hr urine samples were collected after 2 weeks of exposure from these aged mice. Blood samples were analyzed for both 2BE and 2BAA and urine samples were analyzed for 2BAA using GC/MS, and their kinetic parameters were estimated through the curve-fitting method using SAS. Systemically absorbed 2BE was rapidly cleared from blood (t1/2-RAT <10 min; t1/2-MOUSE <5 min after the 1-day exposure) independent of exposure concentration. Proportional increases in AUC2BE relative to increases in exposure concentration indicated linear 2BE kinetics. In contrast, the rate of 2BAA elimination from blood decreased as the exposure concentration increased. Nonproportional increases in AUC2BAA also indicated that 2BAA is eliminated following dose-dependent, nonlinear kinetics. Overall, mice eliminated both 2BE and 2BAA from blood faster than rats. Sex-related differences in 2BAA elimination were most significant with rats, in that females were less efficient in clearing 2BAA from the blood. Differences in renal excretion of 2BAA are possibly responsible for the sex-related difference in the 2BAA blood profiles in rats. As exposure continued, the rates of elimination for both 2BE and 2BAA decreased in both species, resulting in longer residence times in the blood. When 19-month-old naive mice were exposed to 125 ppm, 2BE was rapidly cleared from the systemic circulation, exhibiting clearance profiles similar to young mice. However, old mice eliminated 2BAA from blood >10 times slower than young mice after 1-day of exposure. This delayed elimination of 2BAA in old mice was less obvious after 3 weeks of exposure, suggesting that there might be other factors in addition to the age of animals that could influence the apparent difference in 2BAA kinetics between old and young mice. It was concluded that the elimination kinetics of 2BE and 2BAA following repeated 2BE exposure appear to be dependent on species, sex, age, time of exposure, as well as the exposure concentration.
Chronic inhalation studies with 2-butoxyethanol (BE) conducted by the National Toxicology Program identified the forestomach and liver of B6C3F1 mice as target organs for tumorigenicity. Previous studies have shown that the liver tumors likely resulted from chronic hemolysis-induced oxidative stress. For the forestomach lesions seen in mice, chronic contact irritation (cytotoxicity) and regenerative hyperplasia are hypothesized to result in forestomach tumor development. To test this hypothesis, several experiments were conducted to address the sensitivity of the mouse forestomach to BE administered by various routes. Oral administration of undiluted BE was shown to cause irritation and a compensatory proliferative response in the mouse forestomach, confirming that direct contact between the forestomach and BE, which can occur via grooming of BE condensed on the fur during inhalation exposures, can cause irritation. However, only small amounts of BE (<10 mg/kg) were detected on the fur of mice at the end of 6-hr, whole-body or nose-only inhalation exposures to the highest concentration used in the NTP chronic inhalation studies (250 ppm). Furthermore, no significant differences were detected in the end-exposure blood concentrations of BE and butoxyacetic acid (BAA) between these types of exposures. In addition, parenteral administration of BE (ip and sc injection) also resulted in forestomach lesions, indicating that there may be sources other than grooming for BE- or BAA-induced forestomach irritation. In the pharmacokinetic study, BE and, to a lesser extent, BAA was eliminated more slowly from the forestomach tissue of mice than from blood or other tissues, following either oral gavage or ip injection. The forestomach was the only tissue with detectable levels of BE at 24 hr. BE and BAA were both excreted in the saliva and were present in stomach contents for a prolonged period of time following these routes of exposure, which may further contribute to forestomach tissue dosimetry. Thus, there appear to be multiple mechanisms behind the increased levels of BE and BAA in the forestomach tissue of mice, which together can contribute to a prolonged contact irritation, compensatory hyperplasia, and tumorigenicity in mice. The relevance of these effects in humans, who lack a forestomach, is questionable.
A total of 16 male Sprague-Dawley rats were continuously exposed to 20 ppm or 100 ppm butoxyethanol vapor for 1, 2, 3, 4, 6, 8, 10, or 12 days. Urine was collected in 24-hr intervals and stored at -70 degrees C. At the end of the exposure the animals were euthanized by decapitation and tissue samples of blood, muscle, liver and were rapidly collected and frozen to -70 degrees C. The samples were later derivatized and analyzed for butoxyethanol and its major metabolite butoxyacetic acid by electron capture gas chromatography. Butoxyethanol and butoxyacetic acid were rapidly distributed to the tissues examined. The concentration of butoxyethanol in blood was slightly higher, and that of butoxyacetic acid markedly higher than in other tissues, indicating weak (butoxyethanol) and pronounced (butoxyacetic acid) blood protein binding, respectively. Butoxyethanol was efficiently metabolized and the blood clearance averaged 2.6 L/hr per kg, corresponding to a hepatic extraction ratio of about 0.75. The renal clearance of butoxyacetic acid (average 0.53 L/hr per kg) corresponded to approximately 15% of the renal blood flow. The kinetics of butoxyethanol and butoxyacetic acid were linear up to 100 ppm. There were no clear indications of changes in the toxicokinetics, such as metabolic induction or inhibition of metabolism or excretion, during the course of the exposure. The recovery of butoxyacetic acid in urine was 64% of the calculated inhaled amount of butoxyethanol, on an equimolar basis.
In humans exposed to 20 ppm (96.6 mg/cu m) 2-butoxyethanol for 2 hr via inhalation, the concentration of 2-butoxyethanol in the blood reached a plateau of 7.4 uM/L within 1-2 hr, and the chemical could no longer be detected in the blood 2-4 hr after exposure. The mean elimination half-time was 40 min. Less than 0.03% of the total uptake of 2-butoxyethanol was excreted in the urine, whereas urinary excretion as 2-butoxyacetic acid ranged from 17% to 55%.
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] 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.
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.
式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
DIHYDROPYRIDAZINE-3,5-DIONE DERIVATIVE AND PHARMACEUTICALS CONTAINING THE SAME
申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA
公开号：US20160002251A1
公开（公告）日：2016-01-07
The present invention provides a dihydropyridazine-3,5-dione derivative or a salt thereof, or a solvate of the compound or the salt, a pharmaceutical drug, a pharmaceutical composition, a sodium-dependent phosphate transporter inhibitor, and a preventive and/or therapeutic agent for hyperphosphatemia, secondary hyperparathyroidism, chronic renal failure, chronic kidney disease, and arteriosclerosis associated with vascular calcification comprising the compound as an active ingredient, and a method for prevention and/or treatment.
SYNTHESIS OF MORPHOLINO OLIGOMERS USING DOUBLY PROTECTED GUANINE MORPHOLINO SUBUNITS
申请人：REEVES MATTHEW DALE
公开号：US20090131624A1
公开（公告）日：2009-05-21
Morpholino compounds are provided having the structure:
where
R
1
is selected from the group consisting of lower alkyl, di(lower alkyl)amino, and phenyl;
R
2
is selected from the group consisting of lower alkyl, monocyclic arylmethyl, and monocyclic (aryloxy)methyl;
R
3
is selected from the group consisting of triarylmethyl and hydrogen; and
Y is selected from the group consisting of: a protected or unprotected hydroxyl or amino group; a chlorophosphoramidate group; and a phosphorodiamidate linkage to the ring nitrogen of a further morpholino compound or a morpholino oligomer. Such compounds include doubly protected morpholino guanine (MoG) monomers. Also described is their use in synthesis of morpholino oligomers.
TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
申请人：Arvinas, Inc.
公开号：US20180125821A1
公开（公告）日：2018-05-10
The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
