The first solvent
It refers to a solvent that is known to cause cancer and strongly suspected to be harmful to people and the environment. If possible, the use of this solvent should be avoided. If this kind of solvent is inevitably used to produce drugs with great therapeutic value, unless its rationality can be proved, the residual amount must be controlled within the specified range, such as:
Benzene (2ppm), carbon tetrachloride (4ppm), 1, 2- dichloroethane (5ppm), 1, 1- dichloroethane (8ppm), 1, 1- trichloroethane.
The second solvent
It refers to a solvent that is not genotoxic to animals but carcinogenic. According to the daily dose 10g, the daily allowable exposure is as follows:
2-methoxyethanol (50ppm), chloroform (60ppm), 1, 1, 2- trichloroethylene (80ppm), 1, 2- dimethoxyethane (100ppm), 1, 2,2. 4- tetralin (100ppm), 2- ethoxyethanol (160ppm), sulfolane (168 dichloromethane (600ppm), ethylene glycol (620ppm), n, n-dimethylformamide (880ppm). 2- dichloroethylene (1870ppm), xylene (2 170ppm), methanol (3000ppm), cyclohexane (3880ppm), n-methylpyrrolidone (4840ppm), etc.
The third solvent
Refers to the solvent with low toxicity to human body. Acute or short-term studies show that these solvents have low toxicity and the results of genotoxicity studies are negative, but there are no data on the long-term toxicity or carcinogenicity of these solvents. The amount of residual solvent is not higher than 0.5%, which is acceptable and indisputable, but it must be proved to be reasonable if it is higher than this value. These solvents include:
Pentane, formic acid, acetic acid, ether, acetone, anisole, 1- propanol, 2- propanol, 1- butanol, 2- butanol, amyl alcohol, butyl acetate, tributyl ether, isopropyl acetate, methyl ethyl ketone, dimethyl sulfoxide, cumene, ethyl acetate, ethyl formate, isopropyl acetate.
In addition to the above three solvents, other solvents are commonly used in the production of drugs, excipients and drugs, such as 1, 1- diethoxypropane, 1-dimethoxymethane, 2,2-dimethoxypropane, isooctane, isopropyl ether and methyl isobutyl ketone. There are no toxicological data based on daily allowable doses of these solvents. If these solvents need to be used in production, their rationality must be proved.
Source/Data /2006/083 1/ Article _ 770.htm
Boiling point, solubility and toxicity of common solvents
Boiling point, solubility and toxicity of common solvents
Solvent name boiling point (10 1.3kPa) solubility toxicity
Special solubility of liquid ammonia at -33.35℃: it can dissolve alkali metals and alkaline earth metals with high toxicity and corrosiveness.
Liquid sulfur dioxide-10.08 dissolves amine, ether, alcohol phenol, organic acid, aromatic hydrocarbon, bromine and carbon disulfide, and most saturated hydrocarbons are insoluble, which is highly toxic.
Methylamine -6.3 is an excellent solvent for most organic and inorganic substances. Liquid methylamine is miscible with water, ether, benzene, acetone and lower alcohol, and its hydrochloride is soluble in water but insoluble in alcohol, ether, ketone, chloroform and ethyl acetate, which is moderately toxic and flammable.
Dimethylamine 7.4 is an excellent solvent for organic and inorganic substances, and it is strongly irritating when dissolved in water, lower alcohols, ethers and low polar solvents.
Petroleum ether is insoluble in water, but miscible with higher alcohols such as acetone, ether, ethyl acetate, benzene, chloroform and methanol, similar to lower alkanes.
Ether 34.6 is slightly soluble in water, easily soluble in hydrochloric acid, and miscible with most organic solvents such as alcohol, ether, petroleum ether, benzene and chloroform.
Pentane 36. 1 is miscible with most organic solvents such as ethanol and ether, and has low toxicity.
Dichloromethane 39.75 is mixed with alcohol, ether, chloroform, benzene, carbon disulfide and other organic solvents with low toxicity and strong anesthesia.
Carbon disulfide 46.23 is slightly soluble in water and miscible with many organic solvents, which is narcotic and highly irritating.
The solvent petroleum brain is more miscible with ethanol, acetone and amyl alcohol than other petroleum solvents.
Acetone 56. 12 is mixed with water, alcohol, ether and hydrocarbon, which has lower toxicity and is similar to ethanol, but its volume is larger.
1, 1- dichloroethane 57.28 is miscible with most organic solvents such as alcohol and ether, with low toxicity and local irritation.
Chloroform 6 1. 15 is mixed with ethanol, ether, petroleum ether, halogenated hydrocarbon, carbon tetrachloride, carbon disulfide, etc. It has moderate toxicity and strong anesthesia.
Methanol 64.5 is mixed with water, ether, alcohol, ester, halogenated hydrocarbon, benzene and ketone, which is moderately toxic and anesthetic.
Tetrahydrofuran 66 is an excellent solvent, miscible with water, easily soluble in ethanol, ether, aliphatic hydrocarbons, aromatic hydrocarbons and chlorinated hydrocarbons, slightly toxic when inhaled and low toxic when taken orally.
Hexane 68.7 is partially soluble in methanol, ethanol, ether acetone higher than ethanol, and chloroform, which is less toxic. Anesthetic, irritating
Trifluoroacetic acid 7 1.78 is miscible with water, ethanol, ether, acetone, benzene, carbon tetrachloride and hexane, and dissolves various aliphatic and aromatic compounds.
1, 1, 1- trichloroethane 74.0 is miscible with organic solvents such as acetone, methanol, ether, benzene and carbon tetrachloride.
Carbon tetrachloride 76.75 is mixed with alcohol, ether, petroleum ether, petroleum brain, glacial acetic acid, carbon disulfide and chlorinated hydrocarbons to dissolve methyl chloride, which is the most toxic.
Ethyl acetate 77. 1 12 can be dissolved in most organic solvents such as ethanol, ether, chloroform, acetone, benzene, etc. And can dissolve some metal salts with low toxicity and anesthesia.
Ethanol 78.3 is miscible with organic solvents such as water, ether, chloroform, esters and hydrocarbon derivatives, and it is narcotic.
Butanone 79.64 is similar to acetone, miscible with most organic solvents such as alcohol, ether and benzene, and has lower toxicity and stronger toxicity than acetone.
Benzene 80. 10 is insoluble in water, but miscible with most organic substances such as glycerol, ethylene glycol, ethanol, chloroform, ether, carbon tetrachloride, carbon disulfide, acetone, toluene, xylene, glacial acetic acid and aliphatic hydrocarbons.
Cyclohexane 80.72 is miscible with ethanol, higher alcohols, ethers, acetone, hydrocarbons, chlorinated hydrocarbons, higher fatty acids and amines, with low toxicity and central inhibition.
Acetone 8 1.60 is miscible with water, methanol, methyl acetate, ethyl acetate, acetone, ether, chloroform, carbon tetrachloride, vinyl chloride and various unsaturated hydrocarbons, but it is moderately toxic when it is immiscible with saturated hydrocarbons, and a large amount of vapor is inhaled, causing acute poisoning.
Isopropanol 82.40 is slightly toxic when mixed with ethanol, ether, chloroform and water, similar to ethanol.
1, 2- dichloroethane 83.48 is mixed with various organic solvents such as ethanol, ether, chloroform and carbon tetrachloride, which is highly toxic and carcinogenic.
Ethylene glycol dimethyl ether 85.2 is soluble in water and can be mixed with many organic solvents such as alcohol, ether, ketone, ester, hydrocarbon and chlorinated hydrocarbon. It can dissolve various resins, and has excellent solvent inhalation and low toxicity to gases such as sulfur dioxide, methyl chloride and ethylene.
Trichloroethylene 87. 19 is insoluble in water, but miscible with ethanol, ether, acetone, benzene, ethyl acetate, aliphatic chlorinated hydrocarbons and gasoline.
Triethylamine 89.6 water: 18.7 or less miscible, slightly soluble above. Soluble in chloroform and acetone, soluble in ethanol and ether, explosive, strongly irritating to skin and mucosa.
Alanine 97.35 dissolves organic substances such as ethanol, ether, DMF and ethylenediamine, and forms addition organic substances with various metal salts, which is very toxic and similar to hydrocyanic acid.
Heptane 98.4 is similar to hexane in low toxicity, low irritation and low anesthesia.
Water 100 omitted
Nitromethane 10 1.2 mixed with alcohol, ether, carbon tetrachloride, DMF, etc. is anesthetic and irritating.
1, 4- dioxane 10 1.32 is miscible with water and most organic solvents, and its solubility is still very strong, slightly toxic, 2-3 times stronger than that of ether.
Toluene 1 10.63 is insoluble in water, but miscible with organic solvents such as methanol, ethanol, chloroform, acetone, ether, glacial acetic acid and benzene. It has an anesthetic effect.
Nitroethane 1 14.0 is miscible with alcohol, ether and chloroform, and has strong local irritation when dissolved in various resins and cellulose derivatives.
Pyridine 1 15.3 is miscible with water, alcohol, ether, petroleum ether, benzene and oil. Soluble in a variety of organic and inorganic substances, with low toxicity and no irritation to skin and mucosa.
4- methyl -2- pentanone 1 15.9 can be miscible with most organic solvents such as ethanol, ether, benzene, animal and vegetable oils, etc., with strong toxicity and local irritation.
Ethylenediamine 1 17.26 is soluble in water, ethanol, benzene and ether, and slightly soluble in heptane, which is irritating to skin and eyes.
Butanol 1 17.7 mixed with alcohol, ether and benzene has low toxicity, which is three times higher than that of ethanol.
Acetic acid 1 18. 1 is soluble in water, ethanol, ether and carbon tetrachloride, but insoluble in carbon disulfide and higher aliphatic hydrocarbons with C 12, with low toxicity and strong toxicity in concentrated solution.
Ethylene glycol monomethyl ether 124.6 is miscible with water, aldehyde, ether, benzene, ethylene glycol, acetone, carbon tetrachloride, DMF and other low toxic substances.
Octane 125.67 is almost insoluble in water, slightly soluble in ethanol, and miscible with ether, acetone, petroleum ether, benzene, chloroform and gasoline, with low toxicity and anesthetic effect.
Butyl acetate 126. 1 1 is an excellent organic solvent, which is widely used in pharmaceutical industry and can also be used as an extractant with little toxicity under general conditions.
The solubility of morpholine 128.94 is stronger than dioxane, benzene and pyridine. Mix with water, dissolve acetone, benzene, ether, methanol, ethanol, ethylene glycol, 2- hexanone, castor oil, turpentine and turpentine to corrode skin, irritate eyes and conjunctiva, and steam can cause liver and kidney diseases.
Chlorobenzene 13 1.69 can be mixed with many organic solvents such as alcohol, ether, aliphatic hydrocarbon, aromatic hydrocarbon and organic chloride, which is lower than benzene and damages the central system.
Ethylene glycol monoethyl ether 135.6 is similar to ethylene glycol monoethyl ether, but less polar, miscible with water, ethanol, ether, carbon tetrachloride and acetone, and it is a low-toxic secondary flammable liquid.
Para-xylene 138.35 is insoluble in water, but can be mixed with organic solvents such as alcohol and ether.
Xylene138.5 ~141.5 is insoluble in water, but miscible with organic solvents such as ethanol, ether, benzene and hydrocarbons, while polar solvents such as ethylene glycol, methanol and chloroethanol partially dissolve a kind of flammable liquid, which is low in toxicity.
M-xylene 139. 10 is insoluble in water, miscible with alcohol, ether and chloroform, and soluble in first-class flammable liquids such as ethyl acetate and DMF at room temperature.
Acetic anhydride 140.0
O-xylene 144.4438+0 is insoluble in water and miscible with first-class flammable liquids such as ethanol, ether and chloroform.
N, N- dimethylformamide 153.0 is miscible with water, alcohol, ether, ketone, unsaturated hydrocarbon and aromatic hydrocarbon. Strong solubility and low toxicity.
Cyclohexanone 155.65 is mixed with organic solvents such as methanol, ethanol, benzene, acetone, hexane, ether, nitrobenzene, petroleum brain, xylene, ethylene glycol, isoamyl acetate, diethylamine, etc., which is anesthetic and has a relatively small poisoning probability.
Cyclohexanol 16 1 is miscible with alcohol, ether, carbon disulfide, acetone, chloroform, benzene, aliphatic hydrocarbon, aromatic hydrocarbon and halogenated hydrocarbon, with low toxicity and no blood toxicity and irritation.
N, N- dimethylacetamide 166. 1 dissolves unsaturated aliphatic hydrocarbons and is miscible with water, ether, ester, ketone and aromatic compounds.
Furfural 16 1.8 is miscible with alcohol, ether, chloroform, acetone and benzene. Partially dissolve low-boiling aliphatic hydrocarbons, and inorganic substances are generally insoluble in drugs, which irritates eyes and tears.
N- methylformamide 180~ 185 is miscible with benzene, soluble in water and alcohol, and insoluble in ether first-class flammable liquids.
Phenol (carbolic acid) 18 1.2 is soluble in ethanol, ether, acetic acid, glycerol, chloroform, carbon disulfide and benzene, but insoluble in hydrocarbon solvents. It is miscible with water above 65.3℃, highly toxic by layering below 65.3℃, highly corrosive to skin and mucosa, and toxic by percutaneous absorption.
1, 2- propanediol 187.3 is miscible with water, ethanol, ether, chloroform, acetone and other organic solvents with low toxicity and easy moisture absorption, so it is not suitable for intravenous injection.
Dimethyl sulfoxide 189.0 mixed with water, methanol, ethanol, ethylene glycol, glycerol, acetaldehyde, acetone, ethyl acetate, pyridine and aromatic hydrocarbon is slightly toxic and irritating to eyes.
O-cresol 190.95 is slightly soluble in water and can be mixed with reference cresols such as ethanol, ether, benzene, chloroform, ethylene glycol and glycerol.
N, N- dimethylaniline 193 is slightly soluble in water, can volatilize with water vapor, and is miscible with alcohol, ether, chloroform and benzene. , and can dissolve a variety of organic substances to inhibit the central and circulatory system, and be poisoned by skin absorption.
Ethylene glycol 197.85 is miscible with water, ethanol, acetone, acetic acid, glycerol and pyridine, soluble in chloroform, ether, benzene and carbon disulfide, insoluble in hydrocarbons and halogenated hydrocarbons, soluble in inorganic substances such as salt and zinc chloride, and has low toxicity, and can be poisoned by skin absorption.
P-cresol 20 1.88 reference cresol reference cresol
N- methylpyrrolidone 202 is miscible with water, except for low-grade aliphatic hydrocarbons, which can dissolve most inorganic, organic and polar gases. Polymer compounds have low toxicity and cannot be taken orally.
M-cresol 202.7 Reference cresol is similar to cresol, reference cresol.
Benzyl alcohol 205.45 is miscible with ethanol, ether and chloroform, and 3.8%(wt) is soluble in water at 20℃, which has low toxicity and little irritation to mucosa.
Cresol 2 10 is slightly soluble in water, but it can be mixed with low toxic substances such as ethanol, ether, benzene, chloroform, ethylene glycol and glycerol, which is corrosive and similar to phenol.
Formamide 2 10.5 is miscible with water, ethanol, ethylene glycol, acetone, acetic acid, dioxane, glycerol and phenol, but hardly soluble in aliphatic hydrocarbons, aromatic hydrocarbons, ethers, halogenated hydrocarbons, chlorobenzene and nitrobenzene, which can stimulate and shock skin absorption.
Nitrobenzene 2 10.9 is almost insoluble in water, but miscible with organic substances such as alcohol, ether and benzene. It is highly toxic to organic matter and can be absorbed through the skin.
Acetamide 22 1. 15 is soluble in water, ethanol, pyridine, chloroform, glycerol, hot benzene, butanone, butanol and benzyl alcohol, and slightly soluble in ether, with low toxicity.
Hexamethyl phosphate triamide 233(HMTA) is soluble in water, complexed with chloroform, and soluble in alcohol, ether, ester, benzene, ketone, hydrocarbon, halogenated hydrocarbon and other toxic substances.
Quinoline 237. 10 is soluble in hot water, dilute acid, ethanol, ether, acetone, benzene, chloroform, carbon disulfide, etc. , moderately toxic, irritating to skin and eyes.
Ethylene glycol carbonate 238 is miscible with hot water, alcohol, benzene, ether, ethyl acetate and acetic acid, and its insoluble toxicity in dry ether, carbon tetrachloride, petroleum ether and CCl4 is low.
Diethylene glycol 244.8 is miscible with water, ethanol, ethylene glycol, acetone, chloroform and furfural, but immiscible with ether and carbon tetrachloride. , slightly toxic, absorbed through the skin, less irritating.
Nitrogen mustard butyrate 267 is soluble in water, easily soluble in ethanol and ether, slightly soluble in carbon disulfide and hexane, and has moderate toxicity.
Sulfolane 287.3 is miscible with almost all organic solvents and can dissolve most organic compounds except aliphatic hydrocarbons.
Glycerol 290.0 is soluble in water and ethanol, but insoluble in ether, chloroform, carbon disulfide, benzene, carbon tetrachloride and petroleum ether, which is harmless to human body.
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