NIOSH REL: TWA 5 ppm (30 mg/m3), STEL 10 ppm, IDLH 100 ppm;
OSHA PEL: C 15 ppm (90 mg/m3); ACGIH TLV: TWA 30 mg/m3, STEL 60 mg/m3.
介电常数：
20.789999999999999
LogP：
1.12-1.56 at 20℃
物理描述：
2,2'-dichlorodiethyl ether appears as a clear colorless liquid with a sweet pleasant or nauseating odor. Flash point 131°F. Denser than water and insoluble in water. Toxic by inhalation and skin absorption. Used in cleaning compounds, paints, textile finishing, and as a general solvent.
颜色/状态：
COLORLESS, CLEAR LIQ
气味：
PUNGENT
蒸汽密度：
4.93 (EPA, 1998) (Relative to Air)
蒸汽压力：
1.55 mm Hg @ 25 °C
自燃温度：
369 °C (696 °F)
分解：
WHEN HEATED TO DECOMP, EMITS HIGHLY TOXIC FUMES OF /HYDROGEN CHLORIDE/.
粘度：
2.0653 cP @ 25 °C
腐蚀性：
NOT VERY CORROSIVE TO IRON, MILD STEEL, OR ALUMINUM.
燃烧热：
(EST) -4180 CAL/G
汽化热：
79.5 CAL/G
表面张力：
37.9 DYNES/CM @ 19 °C
气味阈值：
Odor detection in water= 3.60x10+2 ppm, purity not specified.
MALE RATS GIVEN SINGLE ORAL DOSE OF BIS(2-CHLOROETHYL)ETHER, TWO METABOLITES WERE IDENTIFIED IN URINE SAMPLES: THIODIGLYCOLIC ACID (TDGA) & 2-CHLOROETHYL BETA-D-GLUCURONIC ACID.
MALE RATS WERE GIVEN A SINGLE ORAL DOSE OF 40 MG/KG (14)C-LABELED BIS(2-CHLOROETHYL) ETHER (BCEE). THIODIGLYCOLIC ACID ACCOUNTED FOR APPROX 75% OF THE TOTAL URINARY (14)C COLLECTED AFTER THE (1-(14)C)BIS(2-CHLOROETHYL) ETHER DOSE. LESSER METABOLITES OF BCEE WERE (2-CHLOROETHOXY)ACETIC ACID (5%), AND N-ACETYL-S-(2-(2-CHLOROETHOXY)ETHYL)-L-CYSTEINE (7%).
Either 40 umole or 160 umole DCEE was injected into male Wistar rats and the metabolites, thiodiglycolic acid (TdGA) and hydroxyethyl mercapturic acid (HEMA), were determined in the 24 hr urine specimens. ...
... In a further step, inhalation experiments were performed to determine urinary excretion of the two metabolites after an 8 hr exposure of male Wistar rats to 10, 50, 100, and 500 ppm DCEE ... .
BCEE is absorbed following inhalation exposure, oral administration, as well as contact to the skin. BCEE is distributed through the body, but highest levels are found in the liver, kidney and small intestine, while much lower levels are found in lung, spleen and muscle. BCEE is extensively metabolized to thiodiglycolic acid (TDGA), 2-chloroethoxyacetic acid (CEAA), and N-acetyl-S-[2-(2-chloroethoxy)ethyl]-L-cysteine, with TDGA being the principal endproduct. Smaller amounts of BCEE are metabolized by oxidation or substitution at a chlorine without ether cleavage. Approximately 80% of BCEE administered orally is excreted as TDGA within 48 hours. Smaller amounts are excreted in feces or expired air and only a very small fraction of the dose remains in the body. This indicates that BCEE is effectively excreted, and that it has a low tendency to accumulate in tissues. (L183, A129)
Quantitative information on the kinetics and metabolism of BCEE /bis(2-chloroethyl) ether/... in humans is not available. ... Limited data show that radioactive BCEE administered to rats by inhalation or gavage is rapidly absorbed. ... BCEE is readily metabolized in rats. The principal metabolite is thiodiglycolic acid ... BCEE is eliminated quickly in both rats and rhesus monkeys. ... BCEE is acutely toxic by the oral, inhalation or dermal routes of exposure. ... Exposure of laboratory animals by inhalation to high single concentrations ... resulted in eye irritation as well as congestion, edema, and hemorrhage in the lungs. ... In general, positive results were obtained when ... tested for mutagenicity in vitro. ... /In one study/ there was a significant increase in the incidence of hepatomas (combined benign hepatomas and malignant tumors) compared to unexposed controls. ... Other limited studies in rats and mice using oral gavage, subcutaneous or intraperitoneal injection and skin painting failed to confirm these findings. ... BCEE was found to be irritating to the eyes and nasal passages of humans ... following short term exposure. No epidemiological studies on the effects of long term exposure to BCEE have been reported. ... None of the long term studies in laboratory animals is of sufficient quality to provide quantitative information on either the potential of BCEE to cause cancer or the toxicological effects produced by long term exposure to this substance.
BCEE is extremely meabolized, with thiodiglycolic acid (TDGA) being the principal endproduct. The pathway leading to TDGA formation is uncertain, but probably involves oxidative cleavage of the ether bond to yield chloroacetaldehyde and 2-chloroethanol. (L183)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类：B2组可能的人类致癌物
Cancer Classification: Group B2 Probable Human Carcinogen
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Positive carcinogenicity results in two strains of mice and evidence of mutagenicity. HUMAN CARCINOGENICITY DATA: None.
Evaluation: There is inadequate evidence for the carcinogenicity of bis(2-chloroethyl)ether in humans. There is limited evidence in experimental animals for the carcinogenicity of bis(2-chloroethyl)ether. Overall evaluation: Bis(2-chloroethyl)ether is not classifiable as to its carcinogenicity in humans (Group 3).
MALE RATS WERE GIVEN A SINGLE ORAL DOSE OF 40 MG/KG (14)C-LABELED BIS(2-CHLOROETHYL) ETHER (BCEE). EXCRETION OF (14)CARBON DIOXIDE AND URINARY (14)C FOLLOWED FOR 48 HR. THE TIME REQUIRED TO ELIMINATE ONE HALF OF THE DOSE WAS 12 HR FOR (1-(14)C)BCEE. EXPIRED (14)CARBON DIOXIDE ACCOUNTED FOR 11.5% OF THE DOSE, URINARY (14)C ACCOUNTED FOR 64.7%, AND 2.4% WAS FOUND IN THE FECES.
Either 40 umole or 160 umole DCEE was injected into male Wistar rats and the metabolites, thiodiglycolic acid (TdGA) and hydroxyethyl mercapturic acid (HEMA), were determined in the 24 hr urine specimens. ... Analysis of the metabolites showed that hydroxymethyl mercapturic acid excretion was much lower than the excretion of thiodiglycolic acid following the uptake of DCEE ... .
Heterobicyclic compounds of Formula (I):
or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.
Formula (I)的杂环化合物：
或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
2-OXO-2- (2-PHENYL-5,6,7,8-TETRAHYDRO-INDOLIZIN-3-YL) -ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ANTIFUNGAL AGENTS
申请人：Payne Lloyd James
公开号：US20110009390A1
公开（公告）日：2011-01-13
The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof: wherein: R1, R2, R3, R4, R5, R6, R7, R8, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
