Abstract  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.

Abstract  Fischer 344 rats (10/sex/exposure concentration) and New Zealand white rabbits (7/sex/exposure concentration) were exposed to 0, 15, 50, or 200 ppm (0, 91, 303, or 1212 mg/m super(3)) of dipropylene glycol monomethyl ether (DPGME) for 6 hr/day, 5 days/week for 13 weeks. Criteria of response included general observations, body weights, clinical chemistry, hematology, urinalyses (rats only), necropsy, organ weights, and histopathology. There were no effects attributed to exposure to DPGME at any exposure concentration in either male or female rats or rabbits. Based on the low vapor pressure of DPGME, and results in this 13-week study, DPGME appears to have a low subchronic vapor inhalation toxicity hazard.

Abstract  A solid-phase microextraction (SPME) device was used as a diffusive sampler for airborne propylene glycol ethers (PGEs), including propylene glycol monomethyl ether (PGME), propylene glycol monomethyl ether acetate (PGMEA), and dipropylene glycol monomethyl ether (DPGME). Carboxen-polydimethylsiloxane (CAR/PDMS) SPME fiber was selected for this study. A polytetrafluoroethylene (PTFE) tubing was used as the holder, and the SPME fiber assembly was inserted into the tubing as a diffusive sampler. The diffusion path length and area of the sampler were 0.3 cm and 0.00086 cm(2), respectively. The theoretical sampling constants at 30°C and 1 atm for PGME, PGMEA, and DPGME were 1.50 × 10(-2), 1.23 × 10(-2) and 1.14 × 10(-2) cm(3) min(-1), respectively. For evaluations, known concentrations of PGEs around the threshold limit values/time-weighted average with specific relative humidities (10% and 80%) were generated both by the air bag method and the dynamic generation system, while 15, 30, 60, 120, and 240 min were selected as the time periods for vapor exposures. Comparisons of the SPME diffusive sampling method to Occupational Safety and Health Administration (OSHA) organic Method 99 were performed side-by-side in an exposure chamber at 30°C for PGME. A gas chromatography/flame ionization detector (GC/FID) was used for sample analysis. The experimental sampling constants of the sampler at 30°C were (6.93 ± 0.12) × 10(-1), (4.72 ± 0.03) × 10(-1), and (3.29 ± 0.20) × 10(-1) cm(3) min(-1) for PGME, PGMEA, and DPGME, respectively. The adsorption of chemicals on the stainless steel needle of the SPME fiber was suspected to be one of the reasons why significant differences between theoretical and experimental sampling rates were observed. Correlations between the results for PGME from both SPME device and OSHA organic Method 99 were linear (r = 0.9984) and consistent (slope = 0.97 ± 0.03). Face velocity (0-0.18 m/s) also proved to have no effects on the sampler. However, the effects of temperature and humidity have been observed. Therefore, adjustments of experimental sampling constants at different environmental conditions will be necessary.

Abstract  Acute toxicity and irritation data are tabulated for about 140 synthetic organic compounds, most of them tested before regular production, in a continuing program to predict potential acute hazards to health of accidental human contact with chemicals which may become commercial products.

Abstract  Desalination via forward osmosis using draw agents whose regeneration is aided via liquid-liquid phase separation has gained much attention in recent years. In the present study, mixtures of two different glycol ethers, tripropylene glycol methyl ether and tripropylene glycol n-butyl ether, have been studied as potential draw agents. Water activity, viscosity and diffusion coefficient of draw solutions have been measured at different mixture compositions, concentrations and temperatures. Osmotic pressures of these draw solutions decreases strongly with increasing temperature. Forward osmosis experiments performed with these draw solutions reveal appreciable initial loss of trans-membrane water flux, reverse solute flux and severe concentration polarization.

Abstract  The use of read-across of data within a group of structurally similar substances potentially allows one to characterise the hazards of a substance without resorting to additional animal studies. However the use of read-across is not without challenges, particularly when used to address the needs of a regulatory programme such as the EU REACH regulation. This paper presents a case study where a previously accepted read-across approach was used to address several data gaps in a REACH registration dossier but was subsequently rejected in part by the European Chemicals Agency (ECHA), resulting in the requirement to perform a developmental toxicity study in rodents. Using this case study, this paper illustrates some of the practical challenges faced when making use of read-across, particularly with respect to addressing the uncertainty associated with the use of read-across; showcasing the scientific justification and highlighting some of the potential implications/opportunities for future cases.