When (14)C-chloroform was admin orally to mice, rats, & monkeys, radioactivity was found in expired air. Most of dose was excreted unchanged by monkeys, as (14)CO2 (carbon dioxide) by mice, & as both by rats. Three metabolites were detected in urine of rats & mice, one of which was identified as urea.
Haloforms are metabolized to carbon monoxide by hepatic microsomal mixed function oxidases & this reaction is markedly stimulated by sulfhydryl cmpd. Max stimulation occurred at 0.5 mmol glutathione. A mechanism for conversion to carbon monoxide is proposed.
Deuterium-labeled chloroform was less toxic and less readily metabolized than /normal/ chloroform, suggesting that the cleavage of the C-H bond is the rate-limiting step in the process resulting in hepatotoxicity.
Chloroform in absorbed mainly through the lungs. Once in the body it concentrates in lipid-containing organs such as the adipose tissue, the central nervous system, kidney and liver. It is eliminated unchanged in expired air or metabolized by the liver via a cytochrome P450 mechanism and excreted in the urine and faeces. (A11)
IDENTIFICATION AND USE: Chloroform is a clear, colorless liquid. It is used in the manufacture of fluorcarbon-22. Chloroform is a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, resins. It is also used as cleansing agent, as well as in fire extinguishers to lower the freezing temperature of carbon tetrachloride, and in the rubber industry. Chloroform was formerly used as an anesthetic and in pharmaceutical preparation immediately prior to World War II. However, these uses have been banned. HUMAN STUDIES: In humans, anesthesia with chloroform may result in death due to respiratory and cardiac arrhythmias and failure. Renal tubular necrosis and renal dysfunction have also been observed in humans. Chloroform is irritating to mucous membranes, producing gastroenteritis with persistent nausea and vomiting. Symptoms following ingestion of chloroform are similar to those following inhalation. Cases of severe intoxication after suicidal attempts, with the same pattern of symptoms as after anesthetic use, have been reported. There are considerable inter-individual differences in susceptibility. Some persons presented serious illness after an oral dose of 7.5 g of chloroform, whereas others survived a dose of 270 g chloroform. Long term exposure to concentrations of 100-1,000 mg/cu m (20-200 ppm) of chloroform produce mainly neurological effects, with increased incidence of symptoms such as fatigue, nausea, vomiting, lassitude, dry mouth, and anorexia. Some studies also observed effects on the liver, including jaundice, increased serum enzyme levels, and increased liver size. Exposure to concentrated chloroform vapors causes a stinging sensation in the eye. Splashing of the liquid into the eye evokes burning, pain and redness of the conjunctival tissue. Occasional injury of the corneal epithelium will recover fully within a few days. Dermal contact with chloroform causes chemical dermatitis (symptoms: irritation, reddening, blistering and burns). Chloroform with metabolic activation failed to induce chromosome breakage or sister-chromatid exchanges in human lymphocytes. ANIMAL STUDIES: The oxidative biotransformation of chloroform is catalyzed by cytochrome P-450 to produce trichloromethanol. Loss of HCl from trichloromethanol produces phosgene as a reactive intermediate. The reaction of phosgene with tissue proteins is associated with cell damage and death. The liver is the target organ for acute toxicity in rats and several strains of mice. Liver damage is characterized by early fatty infiltration and balloon cells, progressing to centrilobular necrosis and then massive necrosis. The kidney is the target organ in male mice of other more sensitive strains. The kidney damage starts with hydropic degeneration and progresses to necrosis of the proximal tubules. Mice are more sensitive to chloroform toxicity than rats. The carcinogenic effects of chloroform on the liver and kidney of rodents appear to be closely related to cytotoxic and cell replicative effects observed in the target organs. Chloroform has little, if any, capability to induce gene mutation or other types of direct damage to DNA. Two problems potentially compromise the interpretation of mutagenicity data on chloroform. First, there is a possibility that ethyl and diethylcarbonate, produced by reaction of phosgene with ethanol that is routinely added to U.S.P (US Pharmacopoeia) chloroform, could generate false positive results. Secondly, testing of chloroform must be done in a sealed system because of its volatility, and so studies that did not take this factor into account could give false negative results. There are some limited data to suggest that chloroform is toxic to the fetus but only at doses that are maternally toxic. ECOTOXICITY STUDIES: Levels of chloroform in surface waters are generally low and would not be expected to present a hazard to aquatic organisms. However, higher levels of chloroform in surface water resulting from industrial discharges or spills may be hazardous to the embryo-larval stages of some aquatic species.
Chloroform and the reactive intermediates of chloroform metabolism, especially phosgene, bind covalently and irreversibly to cellular macromolecules and cause cellular damage within the liver and kidney. While the exact mechanism is unknown, phosgene has been shown to react with molecules such as cysteine, deplete hepatic glutathione, form adducts with microsomal proteins, and elevate hepatic enzyme levels. Chloroform has also been shown to block HERG potassium channels, causing cardiac arrest. (L13, A11, A29)
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
Weight-of-Evidence Characterization: Under the 1986 U.S. EPA Guidelines for Carcinogen Risk Assessment, chloroform has been classified as Group B2, probable human carcinogen, based on "sufficient evidence" of carcinogenicity in animals (U.S. EPA, 1998). Under the Proposed Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1996; U.S. EPA, 1999), chloroform is likely to be carcinogenic to humans by all routes of exposure under high-exposure conditions that lead to cytotoxicity and regenerative hyperplasia in susceptible tissues (U.S. EPA, 1998). Chloroform is not likely to be carcinogenic to humans by any route of exposure under exposure conditions that do not cause cytotoxicity and cell regeneration.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of chloroform. There is sufficient evidence in experimental animals for the carcinogenicity of chloroform. Overall evaluation: Chloroform is possibly carcinogenic to humans (Group 2B).
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
氯仿可以通过肺部吸收，从胃肠道以及在一定程度上通过皮肤吸收。吸入途径是人体吸收的主要来源。
Chloroform can be absorbed through lung, from GI tract and to some extent through skin. Inhalation route is ... primary source of ... absorption in man.
Chloroform is rapidly absorbed & distributed to all organs, with relatively high concn in nervous tissue. After intraduodenal injection of (14)C-chloroform to rats, 70% ... was found unchanged in expired air & 4% as (14)CO2(carbon dioxide) during 24 hr. ... Liver and, to much lesser extent, kidney were main organs in which CO2 was formed.
In man, pulmonary excretions of chloroform and its CO2 (carbon dioxide) metab account substantially for single oral dose of 0.5 or 1.0 g. Amongst 9 subjects, up to 68% of dose is excreted unchanged & up to 51% of CO2; not more than 4% of dose is excreted unchanged after 8 hr.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
氯仿迅速穿过胎盘并进入胎儿循环。
... /Chloroform crosses/ placenta rapidly and enters fetal circulation.
Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
申请人：Abbott Laboratories
公开号：US20040116518A1
公开（公告）日：2004-06-17
The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases and cerebral vasospasm, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
Some Aspects of the Azide-Alkyne 1,3-Dipolar Cycloaddition Reaction
作者：N. T. Pokhodylo、M. A. Tupychak、O. Ya. Shyyka、M. D. Obushak
DOI：10.1134/s1070428019090082
日期：2019.9
Some peculiar features of two most commonly used catalytic systems (Cul and CuSOVsodium ascorbate) controlling the regioselectivity of 1,3-dipolar cycloaddition of azides to terminal alkynes have been studied. Their potentialities, main disadvantages, and limitations have been demonstrated by a number of examples, including reactions of low-molecular-weight azides and alkynes containing heterocyclic
M(OAc)2 (M = Ca(II), Sr(II) and Ba(II)). In the crystal structures, the three metal(II) atoms occupy both the N2O2 and O6 sites of the ligand (L)4− moiety. Owing to the different nature of the N2O2 and O6 sites of the ligand H4L, the introduction of two different metal(II) atoms to the site-selective moiety, when compared with complex 1, leads to the replacement of the central Co(II) atom by different
4-[(bicycle heterocyclyl)-methyl and -hetero]-piperidines
申请人：Janssen Pharmaceutica, N.V.
公开号：US04695575A1
公开（公告）日：1987-09-22
4-[(Bicyclic heterocyclyl)methyl and -hetero]-piperidines having antihistaminic and serotonin-antagonistic properties which compounds are useful agents in the treatment of allergic diseases.
Dynamic Kinetic Resolution of Alcohols by Enantioselective Silylation Enabled by Two Orthogonal Transition‐Metal Catalysts
作者：Jan Seliger、Martin Oestreich
DOI：10.1002/anie.202010484
日期：2021.1.4
A nonenzymatic dynamic kinetic resolution of acyclic and cyclic benzylic alcohols is reported. The approach merges rapid transition‐metal‐catalyzedalcoholracemization and enantioselective Cu‐H‐catalyzed dehydrogenative Si‐O coupling of alcohols and hydrosilanes. The catalytic processes are orthogonal, and the racemization catalyst does not promote any background reactions such as the racemization
