Glycol Ethers: Ethers of Propylene, Butylene Glycols, and Other Glycol Derivatives

There are five U.S. manufacturers of propylene glycol ether derivatives shown in Table 1. This table also lists the trade names for these materials. The ethers of mono-, di-, tri-, and polypropylene glycol are prepared commercially by reacting propylene oxide with the alcohol of choice in the presence of a catalyst. They may also be prepared by direct alkylation of the selected glycol with an appropriate alkylating agent such as a dialkyl sulfate in the presence of an alkali. The monoalkyl ethers of propylene glycol occur in two isomeric forms, the alpha or beta isomer. The alpha isomer is a secondary alcohol (on the middle carbon of the propane backbone) that forms the ether linkage at the terminal alcohol of propylyene glycol. This alpha isomer is predominant during synthesis. The beta isomer is a primary alcohol with the ether linkage formed at the secondary alcohol. The toxicological significance of the alpha and beta isomers of propylene glycol is discussed later in this narrative. The monoalkyl ethers of dipropylene glycol occur in four isomeric forms. The commercial product Dowanol® DPM Glycol Ether is believed to be a mixture of these but to consist to a very large extent of the isomer in which the alkyl group has replaced the hydrogen of the primary hydroxyl group of the dipropylene glycol, which is a secondary alcohol. The internal ether linkage is between the 2 position of the alkyl-etherized propylene unit and the primary carbon of the other propylene unit, thus leaving the remaining secondary hydroxyl group unsubstituted. In the case of dipropylene glycol monomethyl ether, the primary isomer is 1-(2-methoxy-1-methylethoxy)-2-propanol. The monoalkyl ethers of tripropylene glycol can appear in eight isomeric forms. The commercial product Dowanol® TPM Glycol Ether, however, is believed to be a mixture of isomers consisting largely of the one in which the alkyl group displaces the hydrogen of the primary hydroxyl group of the tripropylene glycol and the internal ether linkages are between secondary and primary carbons. The known physical properties of the most common ethers are given in Tables 5 and 8. The methyl and ethyl ethers of these propylene glycols are miscible with both water and a great variety of organic solvents. The butyl ethers have limited water solubility but are miscible with most organic solvents. This mutual solvency makes them valuable as coupling, coalescing, and dispersing agents. These glycol ethers have found applications as solvents for surface coatings, inks, lacquers, paints, resins, dyes, agricultural chemicals, and other oils and greases. The di- and tripropylene series also are used as ingredients in hydraulic brake fluids. Occupational exposure would normally be limited to dermal and/or inhalation exposure. The toxicological activity of the propylene glycol-based ethers generally indicates a low order of toxicity. Under typical conditions of exposure and use, propylene glycol ethers pose little hazard. As with many other solvents, appropriate precautions should be employed to minimize dermal and eye contact and to avoid prolonged or repeated exposures to high vapor concentrations. The propylene glycol ethers (PGEs), even at much higher exposure levels, do not cause the types of toxicity produced by certain of the lower molecular weight ethylene glycol ethers (EGEs). Specifically, they do not cause damage to the thymus, testes, kidneys, blood, and blood-forming tissues as seen with ethylene glycol methyl and ethyl ethers. In addition, the propylene glycol ethers induce neither the development effects of certain of the methyl- and ethyl-substituted ethylene glycol-based ethers nor the hemolysis and associated secondary effects seen in laboratory animals with EGEs. Other propylene glycol ethers also exhibit a similar lack of toxicity. For example, propylene glycol ethyl ether (PGEE) and its acetate do not cause the critical toxicities of testicular, thymic, or blood injury and do not produce birth defects. Propylene glycol tertiary-butyl ether (PGTBE) also has been tested and fails to elicit these toxicities or birth defects in rats exposed by inhalation to substantial concentrations. The methyl, ethyl, and n-butyl ethers of butylene glycol considered herein are prepared by reacting the appropriate alcohol with the so-called straight-chain butylene oxide, consisting of about 80% 1,2 isomer and about 20% 2,3 isomer in the presence of a catalyst. They are colorless liquids with slight, pleasant odors. The methyl and ethyl ethers are miscible with water, but the butyl ether has limited solubility. All are miscible with many organic solvents and oils; thus, they are useful as mutual solvents, dispersing agents, and solvents for inks, resins, lacquers, oils, and greases. Industrial exposure may occur by any of the common routes. The common esters and diesters of the polyols are prepared commercially by esterifying the particular polyol with the acid, acid anhydride, or acid chloride of choice in the presence of a catalyst. Mono- or diesters result, depending on the proportions of each reactant employed. The ether esters are prepared by esterifying the glycol ether in a similar manner. Other methods can also be used. The acetic acid esters have remarkable solvent properties for oils, greases, inks, adhesives, and resins. They are widely used in lacquers, enamels, dopes, adhesives, and in fluids to dissolve plastics or resins as applied by lacquer, paint, and varnish removers. Generally speaking, the fatty acid esters of the glycols and glycol ethers, in either the liquid or vapor state, are more irritating to the mucous membranes than those of the parent glycol or glycol ethers. However, once absorbed into the body, the esters are hydrolyzed and the systemic effect is quite typical of the parent glycol or glycol ethers. It should be noted that the nitric acid esters of glycols are highly toxic and exert a physiological action quite different from that of the parent polyols. The nitric acid esters of glycols are not typical of the esters or ether esters of organic acids and are considered separately in this chapter. They are used as explosives, usually in combination with nitroglycerin, to reduce the freezing point. Industrial exposures of consequence are most likely to occur through the inhalation of vapors, but may also occur through contact with the eyes and skin. With the dinitrate, a serious hazard exists from absorption through the skin. Keywords: propylene glycol ethers; butylene glycols; glycol esters; glycol diesters; glycol ether esters; ethylene glycol nitrate esters; propylene glycol nitrate esters