Ethylene oxide appears as a clear colorless gas with an ethereal odor with a flash point below 0°F. Liquid less dense than water. Vapors heavier than air. May polymerize exothermically if heated or contaminated. If the polymerization takes place inside a container, the container may rupture violently. Vapors very toxic. Vapors irritate the eyes, skin, and respiratory system. Prolonged skin contact may result in delayed burns. Used to make other chemicals, as a fumigant and industrial sterilant.
颜色/状态：
Colorless ... gas at ordinary room temp and pressure; liquid below 12 °C
气味：
Sweet
闪点：
-20 °F (-29 °C) (closed cup)
溶解度：
Miscible (NTP, 1992)
蒸汽密度：
1.49 (EPA, 1998) (Relative to Air)
蒸汽压力：
1,310 mm Hg at 25 °C (extrapolated)
亨利常数：
Henry's Law constant = 1.48X10-4 atm-cu m/mol at 25 °C
Liquid ethylene oxide is not detonable, but the vapor may be readily initiated into explosive decomposition.
粘度：
9.45X10-3 mPa.s (25 °C, gas) and 0.254 mPa.s (10 °C, liquid)
燃烧热：
1280.9 kJ/mol (liquid); 1306.1 kJ/mol (gas)
汽化热：
24.75 kJ/mol at 25 °C
电离电位：
10.56 eV
聚合：
Precautions designed to prevent explosive polymerization of ethylene oxide are discussed, including rigid exclusion of acids, covalent halides such as aluminium, iron (III), and tin (IV) chloride, basic materials like alkali hydroxides, ammonia, amines, metallic potassium, and catalytically active solids such as aluminium or iron oxides or rust.
Ethylene oxide reacts with glutathione to form cysteine derivatives, forms ethylene glycol by epoxide hydrolase with subsequent metabolism of the glycol, and reacts with chloride to form 2-chloroethanol. The relative importance of these pathways is undefined. Ethylene glycol glutathione conjugates are metabolites of ethylene oxide. ...
In adult male Sprague-Dawley rats, male Swiss CD-1 mice, and male rabbits, 20 or 60 mg/kg ethylene oxide as a solution in distilled water was injected into the caudal vein in rats and mice or in the marginal vein in rabbits. Some animals were exposed to 200 ppm ethylene oxide in inhalation chambers. The animals were housed in metabolism cages, and urine samples were collected at 0-6 hr and 6-24 hr. The urine samples were analyzed for 2-hydroxyethylmercapturic acid, N-acetyl-S-carboxy-methyl-L cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol. Species-related differences in the metabolic disposition of ethylene oxide were observed. Excretion product patterns did not differ significantly between injected doses. Rats (n= 5) eliminated 37% of ethylene oxide as 2-hydroxyethylmercapturic acid (31%) and ethylene glycol (6%); mice (n= 10) converted 19.3% of the ethylene oxide to 2-hydroxyethylmercapturic acid (8.3%), S-2-hydroxyethyl-L-cysteine (5.8%), S-carboxymethyl-L-cysteine (1.9%), and ethylene glycol (3.3%). The rabbits (n= 3) excreted only 2% of the ethylene oxide, primarily as ethylene glycol. In rats, larger amounts of 2-hydroxyethylmercapturic acid were excreted in the 6-24 hr period, and larger amounts of ethylene glycol were excreted in the 0-6 hr period. In mice, equal amounts of 3-hydroxyethylmercapturic acid were excreted in the two collection periods and larger amounts of ethylene glycol were excreted in the 6-24 hr period. No urine was voided by the rabbits in the 0-6 hr period. No qualitative differences in urinary metabolite excretion of ethylene oxide were observed relative to the method of exposure.
In the presence of water and chloride, ethylene oxide is hydrolyzed to 2-chloroethanol and ethylene glycol. The glycol is further metabolized to oxalate, formic acid and CO2.
Within 24 hours following iv treatment 35% of the administered doses ranging from 1 to 10 mg/kg to the rat were excreted as 2-hydroxyethyl-mercapturic acid (2-HEMA) in the urine. After inhalation exposure to different ethylene oxide concentrations, the 2-HEMA levels determined in 24 hr-urine were linearly related to ethylene oxide exposure levels.
In animals and humans, there are two routes of ethylene oxide catabolism, both of which are considered to be detoxification pathways. The first involves hydrolysis to ethylene glycol, with subsequent conversion to oxalic acid, formic acid, and carbon dioxide. The second involves conjugation with glutathione, with subsequent metabolic steps yielding S-(2-hydroxyethyl)cysteine (S-(2-carboxymethyl)cysteine) and N-acetylated derivatives (ie, N-acetyl-S-(2-hydroxyethyl)cysteine (and N-acetyl-S-(2-carboxymethyl)cysteine)) ... . The route involving conjugation with glutathione appears to predominate in rats and mice; in larger species (rabbits, dogs), the conversion of ethylene oxide is primarily via hydrolysis through ethylene glycol ... . Ethylene oxide may also be formed from the metabolism of ethylene ... . A physiologically based pharmacokinetic (PBPK) model for the dosimetry of inhaled ethylene oxide was first developed for rats and included binding of ethylene oxide to hemoglobin and DNA in addition to tissue distribution, metabolic pathways (ie, hydrolysis by epoxide hydrolase and conjugation by glutathione-S-transferase), and depletion of hepatic and extra-hepatic glutathione ... . The model was then refined and extended to mice and humans ... . Simulations indicate that in mice, rats, and humans, about 80%, 60%, and 20%, respectively, would be metabolized via glutathione conjugation ... . This is consistent with observed levels of theta-class glutathione S-transferase (GSTT1) enzyme activity in the order mice > rats > humans. In rats and mice, GSTT1 activity was highest in the liver, followed by the kidney and testes. Rat brain and rat and mouse lung contained small amounts of activity compared with other tissues (enzyme activity in mouse brain was not examined). Ethylene oxide is a substrate for the human GSTT1 enzyme ... .
IDENTIFICATION: Ethylene oxide is a colorless, high reactive gas at room temperature and pressure. It used in the manufacture of ethylene glycol and surfactants. It used in the manufacture of surfactants. Ethylene oxide is also used as a sterilant for health care materials and other heat-sensitive products. HUMAN EXPOSURE: Ethylene oxide is rapidly taken up via the lungs, distributed, and metabolized to ethylene glycol and to glutathione conjugates. Ethylene oxide can be absorbed though the skin from the gas phase or from aqueous solutions and is uniformly distributed throughout the body. Ethylene oxide is an alkylating agent and forms protein and DNA adducts. Hemoglobin adducts have been used for biomonitoring. Based on studies primarily in occupationally exposed populations, ethylene oxide is an ocular, respiratory, and dermal irritant and a sensitizing agent. Neurological effects (primarily sensorimotor polyneuropathy) have been observed in workers exposed to relatively high concentrations. The route of likely greatest exposure and focus of the human health is inhalation from air. There is some evidence of an association between exposure to ethylene oxide and the development of haematological cancers in epidemiological studies of occupationally exposed populations, limitations of the data preclude definitive conclusions. There is consistent evidence that ethylene oxide has induced clastogenic changes in exposed workers. ANIMAL/PLANT STUDIES: The acute inhalation toxicity of ethylene oxide in rodents and dogs is low. In inhalation studies, ethylene oxide has induced a wide range of tumours (e.g., leukaemia, lymohoma, brain, lung). Ethylene oxide induces gene mutations at all phylogenetic levels tested in vitro and in vivo. It also induces germ cell mutations and clastogenic effects in experimental animals. In experimental animals, ethylene oxide is fetotoxic in the presence and absence of maternal toxicity at concentrations higher than those associated with cancer and other non-cancer (i.e., neurological) effects; it is teratogenic only at very high concentrations (above about 1600 mg/m3). Evidence from epidemiological studies of reproductive effects (primarily spontaneous abortions) of ethylene oxide in humans is limited. In experimental animals, among non-neoplastic effects, reproductive effects occur at lowest concentration (>90 mg/m3). These include reductions in litter size, increased post-implantation losses, alterations in sperm morphology, and changes in sperm count and motility. Available data on the non-neoplastic effects of repeated exposure to ethylene oxide in studies are limited, with past focus being primarily on the carcinogenicity of the compound. Reported effects in studies in animals were restricted primarily to those on the hematological and nervous systems.
Ethylene oxide is an alkylating agent. The addition of alkyl groups to proteins, DNA, and RNA by binding to the sulfhydryl and hydroxyl, amino, and carboxyl groups, prevents normal cellular metabolism and ultimately kills cells. It is likely that the carcinogenicity of ethylene oxide in laboratory animals arises primarily as a result of its direct alkylation of DNA and RNA. In vivo exposure to ethylene oxide induced mutations (5- to 5.6-fold) at the Hprt locus in splenic T-lymphocytes in rats and mice.
Evaluation: There is limited evidence in humans for the carcinogenicity of ethylene oxide. There is sufficient evidence in experimental animals for the carcinogenicity of ethylene oxide. In making the overall evaluation, the Working Group took into consideration the following supporting evidence. Ethylene oxide is a directly acting alkylating agent that: (1) induces a sensitive, persistent dose-related increase in the frequency of chromosomal aberrations and sister chromatid exchange in peripheral lymphocytes and micronuclei in bone marrow cells of exposed workers; (2) has been associated with malignancies of the lymphatic and hematopoietic system in both humans and experimental animals; (3) induces a dose related increase in the frequency of hemoglobin adducts in exposed humans and dose related increases in the numbers of adducts in DNA and hemoglobin in exposed rodents; (4) induces gene mutations and heritable translocations in germ cells of exposed rodents; and (5) is a powerful mutagen and clastogen at all phylogenetic levels. Overall evaluation: Ethylene oxide is carcinogenic to humans (Group 1).
The study reported here examined the dosimetry of ethylene oxide (EO) in male B6C3F1 mice by direct determination of blood EO concentrations. Steady-state blood EO concentrations were measured during a single 4-hr nose-only inhalation exposure (0, 50, 100, 200, 300, or 400 ppm EO). In addition, glutathione (GSH) concentrations were measured in liver, lung, kidney, and testis to assess the role of the GSH depletion in the saturable metabolism previously observed in mice. Blood EO concentrations were found to increase linearly with exposure concentration up to 200 ppm. Markedly sublinear blood dosimetry was observed at exposure concentrations exceeding 200 ppm. An EO exposure concentration-dependent reduction in tissue GSH levels was observed, with both liver and lung GSH levels significantly depressed at EO exposure concentrations of 100 ppm or greater. /The/ results also indicate that depletion of GSH is likely responsible for nonlinear dosimetry of EO in mice and that GSH depletion corresponds with reports of dose-rate effects in mice exposed to EO.
... The objectives of this study were to examine the relationship between cigarette smoking and hemoglobin adducts derived from ... EO and to investigate whether null genotypes for glutathione transferase (GSTM1 and GSTT1) alter the internal dose of these agents. The hemoglobin adduct ... N-(2-hydroxyethyl)valine (HEVal), which is formed from EO, and GST genotypes were determined in blood samples obtained from 16 nonsmokers and 32 smokers (one to two packs/day). Smoking information was obtained by questionnaire, and plasma cotinine levels were determined by immunoassay. Glutathione transferase null genotypes (GSTM1 and GSTT1) were determined by PCR. ... HEVal levels increased with increased cigarette smoking dose (both self-reported and cotinine-based). ... HEVal levels were also correlated. ... GSTM1 null genotypes had no significant impact on HEVal. However, HEVal levels were significantly elevated in GSTT1-null individuals when normalized to smoking status or cotinine levels. ... The lack of a functional GSTT1 is estimated to increase the internal dose of EO derived from cigarette smoke by 50-70%.
AFTER EXPOSURE OF MICE TO MIXT OF 1,2-(3)H-ETHYLENE OXIDE VAPOR IN AIR FOR 75 MIN, 90-95% OF RADIOACTIVITY WAS ELIMINATED IN 24 HR. HIGHEST CONCN OF RESIDUAL RADIOACTIVITY WERE FOUND IN PROTEIN FRACTIONS OF SPLEEN; SMALLER AMT OCCURRED IN LIVER, KIDNEY, LUNG & TESTIS.
Iv injection of (14)C-labeled ethylene oxide indicated that (14)C concn in the testicle, epididymis and other organs were higher than those in the blood when measured 20 min to 4 hr after exposure. Radioactivity was still present in the epididymis 24 hr after exposure had ended.
The synthesis of simple alkyl substituted spiroacetals by α,α′-alkylation of metalated acetone dimethylhydrazone with appropriate electrophiles and subsequent acid catalyzed cleavage and ring closure of the products is described.
The synthesis of N-alkyl-1H-1,2,4-triazoles from N,N-dialkylhydrazones and nitriles via formal [3+2] cycloaddition including the C-chlorination/nucleophilic addition/cyclisation/dealkylation sequence was developed. This sequential reaction utilising the in situ generation of hydrazonoyl chloride based on the ambiphilic reactivity of hydrazones afforded a variety of multi-substituted N-alkyl-triazoles
The invention relates to a process for preparing alkylene glycols by hydration of alkylene oxides in the presence of polyalkylene glycol dialkyl ethers of the formula
R
1
—O—[—(CH
2
CH
2
O)
m
(CH(CH
3
)CH
2
)—O]
n
—R
2
in which m=0-100, n=0-100, where n+m is at least equal to 1,
R
1
is a C
1
- to C
6
-alkyl radical,
R
2
is a C
1
- to C
6
-alkyl radical, where R
2
may be different from R
1
, with the proviso that for at least 50 mol % of the polyalkylene glycol dialkyl ether m+n is greater than or equal to 11.
该发明涉及一种制备烷基二醇的方法，通过在多烷基乙二醚的存在下水合烷基氧化物来实现，该多烷基乙二醚的化学式为
R
1
—O—[—(CH
2
CH
2
O)
m
(CH(CH
3
)CH
2
)—O]
n
—R
2
其中m=0-100，n=0-100，其中n+m至少等于1，
R
1
是C
1
-到C
6
-烷基基团，
R
2
是C
1
-到C
6
-烷基基团，其中R
2
可能与R
1
不同，但至少对于50摩尔％的多烷基乙二醚，m+n大于或等于11。
4' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
申请人：Dunn Robert
公开号：US20080318941A1
公开（公告）日：2008-12-25
The present disclosure provides compounds having affinity for the 5-HT
6
receptor which are of the formula (I):
wherein R
1
, R
2
, R
5
, R
6
, B, D, E, G, Q, x and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
A convenient synthesis of nitro-substituted 1,2-benzisothiazol-3(2<i>H</i>)-one 1,1-dioxides (nitrosaccharins)
作者：Walfred S. Saari、John E. Schwering
DOI：10.1002/jhet.5570230456
日期：1986.7
Nitro-substituted 1,2-benzisothiazol-3(2H)-one 1,1-dioxides (nitrosaccharins) have been synthesized by amminolysis of nitro 2-chlorosulfonylbenzoate esters. This method appears to have advantages over the original procedure of oxidation of an ortho-toluenesulfonamide.
