Chloroform

CHLOROFORM, Chloroformium (ФУИ), trichloromethane, CHCl₃, a colorless transparent liquid with a characteristic sweetish odor and burning taste. Sp. gr. 1.502 (at 15°), boiling point 61-62°. Chloroform mixes in all proportions with alcohol, ether, fatty and essential oils and is a good solvent for many organic substances (paraffin, resin, rubber, most alkaloids, lecithin, etc.) and some inorganic substances (iodine, sulfur, phosphorus, etc.). Solubility in water is about ¹/₂%. The main methods of preparation: 1) by the action of caustic alkalis on chloral (Liebig): CCl₃CHO+NaOH→CHCl₃+HCOONa; 2) by the action of bleaching powder on ethyl alcohol (Soubeyran); 3) by the electrolysis of alkali chlorides in the presence of alcohol, acetone, etc. Purification of chloroform is carried out by crystallization during freezing (Pictet) or by forming a compound with salicylide, which releases CHCl₃ upon heating (chloroform Anschiitz'a). Due to the importance of purity of the preparation intended for inhalation anesthesia, pharmacopoeias require mandatory tests for the presence of chlorine, hydrochloric acid, and organic impurities. To protect chloroform from decomposition, it should be stored in orange glass bottles. For the same purpose, alcohol is added to it, and sometimes hexamethylenetetramine. The addition of alcohol (up to 0.6-1%) slightly lowers the specific gravity and raises the boiling point of chloroform. Chemically, chloroform is rather unstable. In light, it is oxidized by atmospheric oxygen, forming chlorine, hydrochloric acid, and especially the poisonous phosgene (which is why it is important to avoid chloroform administration in the presence of an open flame, for example, kerosene lighting). Chloroform belongs to the group of narcotic substances (see) of the fatty series, causing a reversible paralysis of all vital functions. This effect is observed in all organisms (bacteria, protozoa, plants, higher animals). The presence of a halogen in the chloroform molecule increases its narcotic properties and at the same time makes it more toxic, and in the toxic effect, the decomposition products of the molecule (chlorine, etc.) probably participate. The local action of chloroform is expressed as irritation of both sensitive nerve endings and other tissue elements. On the skin, liquid chloroform first causes a sensation of cold, associated with its evaporation, then burning and redness, and when protected from evaporation—inflammation with blister formation. On mucous membranes, the irritating effect is even more pronounced, and swallowing chloroform can lead to severe damage to the stomach, bloody vomiting, and diarrhea. Chloroform vapors irritate less but, when inhaled, lead to various reflexes that disrupt respiratory movements, cardiac activity, and other functions. Absorption of chloroform occurs especially easily with its inhalation, which has the greatest practical significance. When chloroform is absorbed by the blood, the largest amount is found in red blood cells (according to recent research, chloroform is mainly captured by hemoglobin). The distribution of chloroform in the body, studied by Nicloux and others, is related to the fat and lipid content of organs. Thus, particularly large amounts of chloroform are found in the central nervous system (if we do not count low-activity tissues, such as the omentum and perirenal adipose tissue). Excretion of chloroform during inhalation anesthesia occurs mainly through the lungs (partially, chloroform is also excreted by the gastric mucosa and in traces by the kidneys). Excretion occurs mainly in the first few hours after anesthesia, with up to 90% of the administered amount being detected. The presence of chloroform breakdown in the body is indicated by increased excretion of chlorides by the kidneys, as well as changes in parenchymal organs (protein and fatty degeneration of the heart, liver, kidneys), albuminuria, etc. Chloroform is used mainly for inhalation anesthesia. (For the theoretical and practical aspects of this use, see the articles General Anesthesia and Narcotic Substances.) The main feature of chloroform anesthesia is the possibility of achieving a deeper anesthesia compared to many other inhalation anesthetic agents, but at the same time, the greater toxicity of the preparation, complicating anesthesia with a number of undesirable phenomena. During anesthesia itself, the greatest importance is the harmful effect of chloroform on cardiac activity, while in the aftermath of anesthesia—more prolonged disturbance of metabolism and degeneration of the heart muscle and parenchymal organs. Inhalation administration of chloroform is used: a) to achieve deep anesthesia during surgical intervention; b) for more superficial anesthesia in various convulsive conditions (tetanus, eclampsia, strychnine poisoning, etc.); c) to suppress painful sensations in the upper respiratory tract, for example, when poisoned by irritating fumes (see Chemical Warfare Agents), in a mixture with menthol, alcohol, etc. Internally, chloroform is prescribed: a) in the form of 0.5% chloroform water (Aqua Chloroformii) for gastralgia, intractable vomiting of pregnancy, etc. (a tablespoon at a time); the dose of pure chloroform for adults is 0.25-0.5 per dose, up to 1.0-3.0 per day; b) in the form of mixtures with syrup of sugar as an anthelmintic (rarely): up to 4.0 within an hour, followed by the prescription of a laxative. Externally: a) in the form of drops with creosote, etc. for toothache (on cotton in a carious tooth); b) in the form of liniments for rheumatic pains. Chloroform is also used to prevent fermentation of urine when sending it for examination (a few drops per 1 liter). First aid for chloroform poisoning—see General Anesthesia and Narcotic Substances. Preparations of chloroform: 1. Chloroformium (Ph. VII), chloroform. Used for various medical purposes, except anesthesia. 2. Chloroformium pro narcosi (Ph. VII), chloroform for anesthesia. Anesthetic chloroform, in addition to the purity tests performed when testing the first preparation, must also withstand additional tests, and its supplies should be subjected to such research every 3 months. In the USSR, chloroform is produced in three grades: pure, anesthetic, and for analysis.

v. Karasik. In histological technique, chloroform is used mainly for hardening pieces embedded in celloidin. This is done as follows. Pieces, previously passed through an alcohol series, are removed from the celloidin, placed on dry wooden blocks boiled several times in soda, and left to stand in the air for about 3 minutes. Then they are either immersed in 95% alcohol with an admixture of chloroform or it is better to use chloroform vapors. In the latter case, the blocks are placed under a glass bell jar in which stands a vessel with evaporating chloroform; an even simpler method is to place the blocks with celloidin objects on the bottom of a wide-mouthed jar with a ground stopper, into which a little chloroform is poured at the bottom. In chloroform vapors, blocks should be kept no more than 3-5 hours, during which time the celloidin hardens and the objects acquire the consistency of cartilage, which makes it possible to section them. It is not recommended to leave pieces in chloroform for too long to avoid the brittleness of celloidin that occurs. The hardened pieces are transferred to 70% alcohol, from which they are taken for sectioning and where they are stored further. In combined celloidin-paraffin embedding, pieces from celloidin are transferred to chloroform, then to oil, where they are cleared until transparent, and then to xylene and embedded in paraffin in the usual way. When embedding in paraffin with chloroform, it is used in the same way as with xylene, benzene, carbon disulfide, and other hydrocarbons as a medium that, on the one hand, mixes with water, and on the other, dissolves paraffin. For sections prepared by the freezing method, chloroform can be recommended as an actively de-fating medium, especially for sections very rich in fat (such as lipoma, adipose tissue, etc.). In this case, treatment with absolute alcohol is performed before and after chloroform. Due to its hardening effect on celloidin, chloroform can be used for dehydrating celloidin sections with absolute alcohol to avoid the undesirable dissolution of celloidin in absolute alcohol. For this purpose, a mixture of equal volumes of absolute alcohol and chloroform is taken. Such a mixture dehydrates well and does not dissolve celloidin at all, even when sections are left in it for a long time. In recent years, chloroform has been used to extract camphor from used cinematographic film, which successfully replace celloidin. For this purpose, the film (after preliminary washing in hot water and drying) is placed in a jar with chloroform, which is then replaced several times with fresh chloroform. See also Histological Technique, Dehydration in Histological Technique, De-fatting.

A. Keetner. Methods for determining chloroform in urine. The urine is acidified with tartaric acid and, after adding several cm³ of ethyl alcohol, the chloroform is distilled into a well-cooled receiver. To a portion of the distillate, a few drops of aniline and 2-3 cm³ of concentrated alcoholic solution of caustic soda are added. Upon heating, an unpleasant-smelling isonitrile is formed if chloroform is present. The sensitivity of the reaction is 1:60,000. 0.1 g of ?-naphthol is dissolved in 10% NaOH, heated to 50°, and a few drops are added to a portion of the distillate—a blue-green coloration indicates the presence of chloroform. For quantitative determination, from 100 cm³ of urine, acidified as described above, 50 cm³ of liquid are distilled into a receiver containing 25 cm³ of alcoholic NaOH solution. The distillation is heated for 45 minutes on a boiling water bath with a reflux condenser, after which it is diluted to 100 cm³ in a volumetric flask. In 10 cm³ of the resulting solution, the amount of chlorine is determined by Volhard's method (see). A blank test is run in parallel. The number of cubic centimeters of silver used in titrating 10 cm³, multiplied by the coefficient 0.0398, gives the amount of chloroform in percentages in 100 cm³ of the urine taken.

A. Kuzkin. Discovery in forensic chemical cases. The internal organs are distilled with steam (see Poisons, isolation). 1. To a portion of the distillate, a few crystals of resorcinol, a few drops of caustic soda solution are added and heated on a boiling water bath—a pink or red coloration. Besides chloroform, this reaction is given by chloral hydrate, formaldehyde, formic acid, and carbon tetrachloride. Therefore, only a negative result of this very sensitive reaction is decisive. 2. A few cubic centimeters of the distillate are mixed with 1-2 drops of aniline and an excess of alcoholic solution of caustic soda and heated—the characteristic smell of phenyl-isonitrile appears. Besides chloroform, this reaction is given by chloral hydrate and carbon tetrachloride. 3. A portion of the distillate is heated with sodium alcoholate (solution of sodium in alcohol). The liquid is diluted with water, acidified with nitric acid, and a solution of silver nitrate is added—a white precipitate of silver chloride, soluble in ammonia. This test is characteristic of all volatile halogen compounds and serves to exclude formaldehyde in reaction 1. To exclude carbon tetrachloride, a reduction reaction is performed. 4. A portion of the distillate is mixed with an excess of caustic soda and a few drops of copper sulfate solution and heated to boiling. If chloroform, chloral hydrate, as well as volatile aldehydes (formaldehyde, acetaldehyde) are present, a yellow or red precipitate of cuprous oxide is obtained. To distinguish chloroform from chloral hydrate, the distillate is extracted with ether. The extract is evaporated to dryness at room temperature. The residue is treated with a small amount of water and with this solution all the above-described reactions are performed. A negative result indicates chloroform, a positive result indicates CHLORAL HYDRATE.