Glycol Ether Derivatives Research Articles

Synthesis and antimalarial activity of ethylene glycol oligomeric ethers of artemisinin

The aim of this study was to synthesize a series of ethylene glycol ether derivatives of the antimalarial drug artemisinin, determine their values for selected physicochemical properties and evaluate their antimalarial activity in vitro against Plasmodium falciparum strains. The ethers were synthesized in a one-step process by coupling ethylene glycol moieties of various chain lengths to carbon C-10 of artemisinin. The aqueous solubility and log D values were determined in phosphate buffered saline (pH 7.4). The derivatives were screened for antimalarial activity alongside artemether and chloroquine against chloroquine-sensitive (D10) and moderately chloroquine-resistant (Dd2) strains of P. falciparum. The aqueous solubility within each series increased as the ethylene glycol chain lengthened. The IC50 values revealed that all the derivatives were active against both D10 and Dd2 strains. All were less potent than artemether irrespective of the strain. However, they proved to be more potent than chloroquine against the resistant strain. Compound 8, featuring three ethylene oxide units, was the most active of all the synthesized ethers. The conjugation of dihydroartemisinin to ethylene glycol units of various chain lengths through etheral linkage led to water-soluble derivatives. The strategy did not result in an increase of antimalarial activity compared with artemether. It is nevertheless a promising approach to further investigate and synthesize water-soluble derivatives of artemisinin that may be more active than artemether by increasing the ethylene glycol chain length.

New toxicity data for the propylene glycol ethers – a commitment to public health and safety

Propylene glycol ethers are a class of solvents used in a wide array of industrial, commercial and consumer applications, such as in paints, cleaners and inks. A robust toxicity database exists for the propylene glycol ethers that provide strong product safety support. Standard toxicity studies conducted under good laboratory practices indicate a lack of genotoxic, developmental and reproductive hazards. Recent testing efforts have primarily focused in two areas: (1) examination of the chronic toxicity/oncogenicity potential of propylene glycol monomethyl ether (PGME) in rats and mice and (2) expansion of the developmental toxicity database to higher molecular weight P-series glycol ether derivatives (i.e. propylene glycol n-propyl ether (PGPE), propylene glycol n-butyl ether (PGBE) and dipropylene glycol n-butyl ether (DPGBE)). In PGME chronic toxicity/oncogenicity studies no treatment-related increases in the incidence of tumors occurred in either species. Like other previously tested P-series derivatives, PGPE, PGBE and DPGBE were negative in rodent and rabbit developmental toxicity studies. Collectively, the toxicity database for P-series glycol ether products continues to support the lack of significant health effects with proper use of the commercial products.

Exposure to glycol ethers in a population of French men evaluated by measurement of urinary alkoxycarboxylic acids.

Glycol ethers are solvents that are present in a large number of products used commercially and domestically. During recent years, ethylene glycol ether derivatives, in particular ethylene glycol methyl ether and ethylene glycol ethyl ether, have been progressively replaced by propylene glycol ether derivatives, which are less toxic. The aim of this study was to estimate the level of exposure to glycol ethers in a sample population of French men employed by the Paris Municipality by measuring the amount of alkoxycarboxylic acid metabolites in their urine. Urine samples were collected at the end of two different working weeks from 109 men, 54 of whom were judged to be occupationally exposed to glycol ether-containing products. Five alkoxyacetic acids (methoxyacetic, ethoxyacetic, n-propoxyacetic, phenoxyacetic, butoxyacetic acids) from ethylene glycol derivatives, and one alkoxypropionic acid (2-methoxypropionic) from a propylene glycol derivative, were simultaneously analysed by gas chromatography coupled to electron-capture detection. 2-Methoxypropionic was the most frequently found alkoxycarboxylic acid. The concentration of this metabolite reached 5.6 mmol/mol creatinine. The second most common alkoxycarboxylic acid was phenoxyacetic (up to 2.3 mmol/mol creatinine). The concentrations of the other alkoxycarboxylic acids were less than 1 mmol/mol creatinine. Although the concentration of alkoxycarboxylic acids was higher among men occupationally exposed to glycol ether-containing products than among unexposed men, the difference was significant only for butoxyacetic acid. Our data suggest that the use and exposure levels of glycol ethers have qualitatively and quantitatively changed dramatically over recent years. Particular attention should be paid in the future to alkoxypropionic acids derived from minor isomers of propylene glycol ether derivatives.

Densities, Viscosities, Speeds of Sound, and Water Solubilities of Some Polypropylene Glycol Ether Derivatives in the Temperature Range 273.15-323.15 K

A series of end-capped polyalkylene glycol (PAG) (n-butyl, n-alkyl-substituted polypropylene glycol) and polypropylene glycols (PPG) (dialkyl-, dihalo-, bis(fluoroalkyl)-substituted polypropylene glycol) were synthesized. Optimum reaction conditions were determined with regard to time, temperature, reaction ratios, and solvents for each of the PAG and PPG derivatives. An investigation was carried out to find their suitability as potentially new sonar transducer fill fluids. The density, viscosity, and speed of sound were measured as a function of temperature, and their solubilities in water were measured for several of these derivatives. The desirable properties of some of these compounds make them potentially important transducer fill fluids

Glove Permeation by Semiconductor Processing Mixtures Containing Glycol-Ether Derivatives

Glove Permeation by Semiconductor Processing Mixtures Containing Glycol-Ether Derivatives

Glove permeation by semiconductor processing mixtures containing glycol-ether derivatives.

Results of permeation tests of several glove materials challenged with semiconductor processing formulations containing glycolether derivatives are described. Commercial glove samples of nitrile rubber (Edmont), natural rubber (Edmont and Baxter), butyl rubber (North), PVC Baxter), a natural rubber/neoprene/nitrile blend (Pioneer), and a natural rubber/neoprene blend (Playtex) were tested according to the ASTM F739-85 permeation test method (open-loop configuration). The liquid formulations examined included a positive photoresist thinner containing 2-ethoxyethyl acetate (2-EEA), n-butyl acetate, and xylene; a positive photoresist containing 2-EEA, n-butyl acetate, xylene, polymer resins, and photoactive compounds; a negative photoresist containing 2-methoxyethanol (2-ME), xylene, and cyclized poly(isoprene); and pure 2-methoxyethyl acetate (2-MEA), which is the solvent used in a commercial electron-beam resist. With the exception of the negative photoresist, butyl rubber provided the highest level of protection against the solvent mixtures tested, with no breakthrough observed after 4 hr of continuous exposure at 25 degrees C. Nitrile rubber provided the highest level of protection against the negative photoresist and reasonably good protection against initial exposure to the other solvent mixtures. Gloves consisting of natural rubber or natural rubber blends provided less protection against the mixtures than either nitrile or butyl rubber. For most of the glove samples, permeation of the glycol-ether derivatives contained in the mixtures was faster than that predicted from the permeation of the pure solvents. Increasing the exposure temperature from 25 to 37 degrees C did not significantly affect the performance of the butyl rubber glove. For the other gloves, however, exposures at 37 degrees C resulted in decreases in breakthrough times of 25-75% and increases in steady-state permeation rates of 80-457% relative to values obtained at 25 degrees C. Repeated exposure of nitrile rubber samples resulted in shorter breakthrough times for all mixture components. In fact, exposure for as little as one-half of the nominal breakthrough time followed by air drying overnight resulted in measurable quantities of one or more of the component solvents at the inner surface of the gloves at the beginning of the next exposure. This effect was not observed with the butyl rubber samples. With the exception of the negative photoresist, heating previously exposed nitrile rubber samples at 70 degrees C for 20 hr prior to retesting reduced or eliminated the effects of residual solvents, permitting reuse of the gloves. The use of thin PVC or natural rubber gloves adjacent to the nitrile gloves provided moderate increases in permeation resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene, p-nitrophenol, sodium selenite, dimethyl phthalate, ethylenethiourea, and four glycol ether derivatives.

Ethylene glycol dimethyl ether (EGdiME), diethylene glycol dimethyl ether (diEGdiME), triethylene glycol dimethyl ether (triEGdiME), diethylene glycol diethyl ether (diEGdiEE), ethylenethiourea (ETU), sodium selenite (SS), dimethyl phthalate (DMP), naphthalene (NAP), or p-nitrophenol (PNP) were administered by gavage for eight consecutive days to female CD-1 mice. Weight loss was insensitive as an index of sublethal adult toxicity and was inadequate for determining a maximum tolerated dose. LD50 values indicate that SS, NAP, and PNP were more toxic (8.4, 353.6, and 625.7 mg/kg, respectively) than the polyglycol ethers, ETU, and DMP (LD50 values ranged from 2525.8 to 6281.9 mg/kg). Each of the compounds was administered on d 7 through 14 to pregnant animals at a single dose estimated to be at or just below the threshold of adult lethality. In such a reproductive study, each of the compounds could be categorized on the basis of the pattern of maternal lethality and fetotoxicity which it produced. The number of dams with complete resorptions was significantly increased after administration of ETU, and no mice in the EGdiME-, diEGdiME-, or triEGdiME-treated groups delivered any viable offspring. Maternal lethality was significant in the EGdiME, triEGdiME, PNP, and NAP groups. There was a slight reduction in the average number of live pups per litter in the diEGdiEE- and PNP-treated groups and a significant reduction in the NAP group. The number dead per litter was increased with diEGdiEE. SS and DMP had no effect on maternal or fetal survival at the doses administered. Individual pup weight at d 1 postpartum was only significantly reduced by diEGdiEE, and no gross congenital abnormalities were detected in neonates from any treatment group. These results provide guidelines for the subsequent toxicity testing of these chemicals.