Diglyme

134.17

134.17

1736101

203-924-4

M4BH3X0MVZ

1357

59726

2252|1993

DTXSID1024621

Colorless liquid

2909199090

27.7

-0.36

≤10(APHA) Liquid

0.9451 g/cm³ @ Temp: 20 °C

-68 °C

162 °C @ Press: 760 Torr

134.6 °F

1.394

Solubility in water: miscible

Flammables area

3 mm Hg ( 20 °C)

4.6 (vs air)

Flammable liquid; burning produces irritating fumes

1.4-17.4%(V)

Mild odor

1.75e-11 cm3/molecule*sec

Henry's Law constant = 5.23X10-7 atm-cu m/mol at 25 °C (est)

Diethylene glycol dimethyl ether dissolves vinyl chloride copolymers, postchlorinated poly (vinyl chloride), polymethacrylate, polystyrene, polychloroprene, and cellulose acetate. It does not dissolve rubber and polyethylene, and swells poly(vinyl chloride). It also dissolves sodium borohydride, other covalent inroganic metal compounds, and sodium.|Hydroxyl radical reaction rate constant = 1.75X10-11 cu cm/molec-sec at 25 °C

Oxidizes readily in air to form unstable peroxides that may explode spontaneously [Bretherick, 1979 p.151-154, 164]. A mixture of liquid air and diethyl ether exploded spontaneously, [MCA Case History 616(1960)]. Water soluble.

Ethers

Peroxidizable Compound

A violent explosion occurred when lithium aluminum hydride was being used to dry diethylene glycol dimethyl ether. The ignition may have occurred due to the presence of large amounts of water or perhaps peroxide formed in the ether. About 75% of the ether had been removed when the explosion occurred, [MCA Case History 1494 (1968)].

Bis(2-methoxyethyl) ether (Diglyme)|B: Compounds that form peroxides on concentration (distillation/evaporation)|2 samples had 1 ppm peroxide; age 1-10+ yrs|Kelly|An explosion occured while an attempt to dry diglyme with LiAlH. Could have been due to a reaction with water or perhaps peroxides. See Cameo.|https://cameochemicals.noaa.gov/chemical/8538

190 °C

III

3

UN 3271 3/PG 3

1

60-61-10-19

53-45

KN3339000

T

Warehouse ventilated, low temperature and dry

Stable. Combustible. Incompatible with strong oxidizing agents. May be air or light sensitive.

P201-P210-P280-P308 + P313-P370 + P378

H226-H360

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Glycol ethers, glycols, ketones, and alcohols undergo violent decomposition in contact with 68-72% perchloric acid|Light, heat and oxygen (air) promote formation of potentially explosive peroxides. These may be removed by stirring with a suspension of iron oxide in aqueous alkali.|Presence of carbon dioxide in solutions of the hydride in dimethyl or bis(2-methoxyethyl) ether can cause a violent decomposition on warming the residue from evaporation. Presence of aluminium chloride tends to increase the vigour of decomposition to explosion. Lithium tetrahydroaluminate may behave similarly, but is generally more stable.|The peroxide-free ether, being dried by distillation at 162 °C under inert atmosphere at ambient pressure, exploded violently when the heating bath temperature had been raised to 200 °C towards the end of distillation. This was attributed to local overheating of an insulating crust of hydride in contact with oxygen-containing organic material.

Hardin BD, Lyon JP; Environmental Health Perspectives 57: 273-5 (1984). Proceedings from a NIOSH symposium on the toxic effects of glycol ethers are reviewed.|European Chemicals Bureau; IUCLID Dataset, bis (2-methoxyethyl) ether (CAS # 111-96-6) p.28-9. Available from the Database Query page at: http://ecb.jrc.it/esis/esis.php as of February 7, 2007.|EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from the Database Query page at: http://www.epa.gov/hpv/pubs/hpvrstp.htm on Diglyme as of February 7, 2007|International Programme on Chemical Safety; Concise International Chemical Assessment Document Number 41: Diethylene Glycol Dimethyl Ether (2002). Available from the Database Query page at: http://www.inchem.org/pages/cicads.html as of February 20, 2007.

This chemical is combustible. (NTP, 1992)|Flammable. Above 51 °C explosive vapour/air mixtures may be formed.

|Danger|H226: Flammable liquid and vapor [Warning Flammable liquids]|P201, P202, P210, P233, P240, P241, P242, P243, P280, P281, P303+P361+P353, P308+P313, P370+P378, P403+P235, P405, and P501|H226 (100%): Flammable liquid and vapor [Warning Flammable liquids]|Aggregated GHS information provided by 796 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|P201, P202, P210, P233, P240, P241, P242, P243, P264, P280, P281, P303+P361+P353, P305+P351+P338, P308+P313, P337+P313, P370+P378, P403+P235, P405, and P501|H303: May be harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P264, P271, P281, P304+P340, P305+P351+P338, P308+P313, P312, P314, P332+P313, P337+P313, P403+P233, P405, and P501

Fire Extinguishing Agents: Dry chemical, foam, carbon dioxide (USCG, 1999)|Use water spray, powder, foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Excerpt from ERG Guide 127 [Flammable Liquids (Water-Miscible)]: As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. LARGE SPILL: Consider initial downwind evacuation for at least 300 meters (1000 feet). FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this material from exposure to light and air, and store it under refrigerated temperatures. (NTP, 1992)

Vinyl (not rubber) gloves; safety goggles. (USCG, 1999)

Combustible

Presence of carbon dioxide in solutions of the hydride in dimethyl or bis(2-methoxyethyl)ether can cause a violent decomposition on warming the residue from evaporation. Presence of aluminum chloride tends to increase the vigour of decomposition to explosion.|Explosive limits , vol% in air: 1.5-17.4

NIOSH recommends reducing exposure to lowest feasible concn & preventing contact with the skin. /Glycol ethers/

Personal protection: filter respirator for organic gases and vapours adapted to the airborne concentration of the substance. Remove all ignition sources. Ventilation. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

Fireproof. Separated from strong oxidants.

A harmful contamination of the air can be reached rather quickly on evaporation of this substance at 20 °C.

The substance is mildly irritating to the eyes, skin and respiratory tract.

Animal tests show that this substance possibly causes toxicity to human reproduction or development.

NO open flames, NO sparks and NO smoking. Above 51 °C use a closed system and ventilation.

AVOID ALL CONTACT!

Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety spectacles.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Diethylene glycol dimethyl ether is produced, as an intermediate or final product, by process units covered under this subpart.

| 1 - Materials that, under emergency conditions, can cause significant irritation.| 2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.| 1 - Materials that in themselves are normally stable but that can become unstable at elevated temperatures and pressures.

Diethylene glycol dimethyl ether was found at concentrations of 400 mg/L in activated sludge from the waste treatment facility of the industry producing the chemical(1).|Diethylene glycol dimethyl ether in diluted vehicle exhaust from a light-duty truck using different fuel types(1). [Table#203]

LD50 Mouse oral 2978 mg/kg bw|LD50 Rat oral 4760 mg/kg bw|LC50 Rat inhalation >11 mg/L/7 hr

... Diethylene glycol dimethyl ether (0, 62.5, 125, 250 or 500 mg/kg/day) was administered to CD-1® mice by gavage (by mouth) on gestational days (gd) 6-15. Mice were monitored daily during treatment for evidence of maternal toxicity and were sacrificed on gd 17 (20-24 confirmed pregnancies per group). ... Diethylene glycol dimethyl ether-treated dams failed to exhibit treatment-related clinical signs, death, or differences from control in corrected maternal body weight gain (i.e., gestational weight gain minus gravid uterine weight) or relative maternal liver weight. However, intact maternal body weight (i.e., including gravid uterine weight) was reduced at 250 and 500 mg diethylene glycol dimethyl ether/kg/day on gd 15 and 17, as were maternal weight gain during treatment and gestation. Gravid uterine weight in diethylene glycol dimethyl ether-treated groups was significantly reduced at all doses in a dose-related manner. There were dose-related and significant increases at 250 and 500 mg/kg/day in the percentage of nonlive implants per litter (4.88%, 8.41%, 7.05%, 12.02% and 50.41% in the vehicle control through high-dose groups, respectively), as well as the percentage of adversely affected implants per litter (5.25%, 8.41%, 9.35%, 32.29% and 96.93% nonlive or malformed in the vehicle control through high-dose groups, respectively). The mean live litter size was significantly less than control at 500 mg/kg/day and was marginally reduced at all lower dose levels. The average fetal body weight per litter was significantly reduced at and above 125 mg diethylene glycol dimethyl ether/kg/day. Examination of fetuses for anatomical malformations revealed a dose-dependent trend toward an increased percentage of malformed live fetuses per litter, and the difference from control was statistically significant in the 250 and 500 mg diethylene glycol dimethyl ether/kg/day groups. The mean percent malformed live fetuses per litter was 0.37%, 0.00%, 2.47%, 23.86% and 95.82% in the vehicle through high-dose groups, respectively. The proportion of litters with gross, visceral or skeletal malformations was increased at the high dose, and the proportion of litters with gross or skeletal malformations was increased in the 250 mg/kg/day group. The types of malformations observed in the present study were quite diverse. Major malformations affected primarily the development of the neural tube, limbs and digits, craniofacial structures, abdominal wall, cardiovascular system, urogenital organs, and both the axial and appendicular skeleton. The two most frequently observed malformations were fused ribs in 74% of high dose fetuses and exencephaly in 54% of high dose fetuses. In summary, exposure of timed-pregnant CD-1® mice to diethylene glycol dimethyl ether throughout major organogenesis produced no notable evidence of maternal toxicity. The lowest dose level, 62.5 mg/kg/day, appeared to be a no observed effect level for indices of fetal development. At higher doses, diethylene glycol dimethyl ether produced profound adverse effects upon fetal growth ( greater than or equal to 125 mg/kg/day), fetal viability (greater than or equal to 250 mg/kg/day), and fetal morphological development (greater than or equal to 250 mg/kg/day). At the highest dose, all 23 litters contained at least one malformed fetus compared to 1 of 21 control litters, and 94% of the high-dose fetuses were malformed compared to 0.35% of the fetuses in the control group. Thus, diethylene glycol dimethyl ether posed an extreme degree of risk to the embryo or fetus at dose levels which did not cause observable toxicity to the maternal organism.|In the present study, diethylene glycol dimethyl ether (0, 25, 50, 100 or 175 mg/kg/day ) was administered by gavage in distilled water to timed-pregnant New Zealand White (NZW) rabbits (15-22 dams/group) during major organogenesis (gestational days (gd) 6-19) based on preliminary rangefinding studies. Treated females were sacrificed on gd 30, uterine contents were examined, and live fetuses examined for malformations. Evidence of maternal toxicity, per se, was observed only at 175 mg/kg/day . At this high dose, the mortality among treated females was 15.4% as compared to 4% among controls. No significant maternal toxicity was observed in the 25 mg/kg/day group, and only minimal maternal toxicity (maternal weight gain during treatment) was observed at 50 mg/kg/day as compared to the vehicle control group. However, even these lower doses appeared to contribute to significant dose-related trends for indices of maternal body weight, weight gain, and gravid uterine weight maternal. The lowest dose of diethylene glycol dimethyl ether (25 mg/kg/day ) appeared to be a no-observed-effect level (NOEL) for developmental toxicity in New Zealand White rabbits. At 50 mg/kg/day , apparent adverse effects on prenatal growth, viability and morphological development were in accord with significant dose-response relationships observed across all groups. At 100 and 175 mg/kg/day , adverse effects upon fetal weight were in accord with significant dose-response relationships, but individual treatment groups did not differ significantly from controls. The incidence of resorptions and malformed live fetuses, as well as other cumulative indices which included these endpoints, were significantly above controls at 100 and 175 mg/kg/day . Major malformations affected the development of the digits, craniofacial structures, abdominal wall, cardiovascular system, urogenital organs and axial skeleton. The most frequently observed individual defects were fusion of ribs to each other (19%), hydronephrosis (23%), and clubbing of the limbs (19%) without underlying bone deformities (i.e., of presumed neuromuscular origin). In conclusion, exposure of New Zealand White rabbits to diethylene glycol dimethyl ether at 25 mg/kg/day during major organogenesis produced no adverse maternal or developmental effects. Doses of 50 and 100 mg/kg/day were associated with adverse developmental effects, but did not produce distinctive evidence of maternal toxicity. The incidence of adverse developmental effects was further increased at a dose associated with increased maternal mortality (e.g., 175 mg/kg/day). The principal manifestations of developmental toxicity were increased resorptions and a higher incidence of major malformations among surviving fetuses.

Diethylene glycol dimethyl ether's production and use as a solvent and an anhydrous reaction medium for organo-metallic synthesis(1) or as a solubilizer(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 15(SRC), determined from a log Kow of -0.36(2) and a regression-derived equation(3), indicates that diethylene glycol dimethyl ether is expected to have very high mobility in soil(SRC). Volatilization of diethylene glycol dimethyl ether from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.2X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 2.96 mm Hg(4), and assigned value for water solubility of 1X10+6 mg/L (miscible)(5). Diethylene glycol dimethyl ether is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Diethylene glycol dimethyl ether was degraded 33% after 25 days and a 7 day lag period using an activated sludge from an industry producing the chemical(6), indicating that biodegradation may be an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 15(SRC), determined from a log Kow of -0.36(2) and a regression-derived equation(3), indicates that diethylene glycol dimethyl ether is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.2X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 2.96 mm Hg(4), and assigned value for water solubility of 1X10+6 mg/L (miscible)(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Diethylene glycol dimethyl ether was biodegraded 33% after 25 days and a 7 day lag period using an activated sludge from an industry producing the chemical(8), indicating that biodegradation may be an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethylene glycol dimethyl ether, which has a vapor pressure of 2.96 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase diethylene glycol dimethyl ether is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 22 hours(SRC), calculated from its rate constant of 1.75X10-11 cu cm/molecule-sec at 25 °C(3). Diethylene glycol dimethyl ether does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

The rate constant for the vapor-phase reaction of diethylene glycol dimethyl ether with photochemically-produced hydroxyl radicals has been measured as 1.75X10-11 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 22 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Diethylene glycol dimethyl ether is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Diethylene glycol dimethyl ether does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(3).

An estimated BCF of 3 was calculated in fish for diethylene glycol dimethyl ether(SRC), using a log Kow of -0.36(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of diethylene glycol dimethyl ether is estimated as 15(SRC), using a log Kow of -0.36(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that diethylene glycol dimethyl ether is expected to have very high mobility in soil.

The Henry's Law constant for diethylene glycol dimethyl ether is estimated as 5.2X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 2.96 mm Hg(1), and assigned value for water solubility of 1X10+6 mg/L (miscible)(2). This Henry's Law constant indicates that diethylene glycol dimethyl ether is expected to be essentially nonvolatile from water surfaces(3). Diethylene glycol dimethyl ether's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). The potential for volatilization of diethylene glycol dimethyl ether from dry soil surfaces may exist(SRC) based upon its vapor pressure(1).

DRINKING WATER: Diethylene glycol dimethyl ether was listed as a contaminant found in drinking water(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 207 workers (52 of these are female) are potentially exposed to diethylene glycol dimethyl ether in the US(1). Occupational exposure to diethylene glycol dimethyl ether may occur through inhalation and dermal contact with this compound at workplaces where diethylene glycol dimethyl ether is produced or used(SRC). Monitoring data indicate that the general population may be exposed to diethylene glycol dimethyl ether via inhalation of vehicle exhaust and ingestion of contaminated drinking water(SRC).

The major route of elimination is through the urine. Ninety-six hours after oral application of 6.84 mg diglyme/kg body weight to male Sprague-Dawley rats, 90% of the dose was excreted via urine, 3.6% as carbon dioxide, and 2.9% in the feces. Only 1.7% of the dose remained in the carcass.|Although the main metabolite in rat urine is 2-methoxyethoxyacetic acid, numerous studies indicate that 2-methoxyacetic acid is the metabolite responsible for the toxicity of diglyme for the male reproductive organs. 2-methoxyacetic acid was transferred to the fetus and found as the sole metabolite in the fetus (no parent compound was detected in the fetus either) after dosing diglyme to mice at day 11 or 12 of pregnancy. The highest levels for the average embryo (whole embryos analysed) were detected at 6 hr after dosing. Significantly lower amounts were detected in blood taken from the dam at that time point.|... The skin absorption rates of a group of glycol ethers /were evaluated/ in vitro ... using the Franz cell method with human skin. ... A permeation profile was obtained and steady state, lag time and permeation constant flux was calculated for ... ethylene glycol diethyl ether (EGDEE) and diethylene glycol dimethyl ether (DEGDME). ... solvents were tested in their pure form and with 70% acetone. ... For all solvents tested the lag time was less than 2 hr, and for the majority of them was about 60 min ... Flux at steady state ranged between 0.017 +/- 0.005 and 3.435 +/- 1.897 mg/cm(2)/hr and permeation rate was from 0.0192 to 1.02 x 10(-3) cm/hr ...

The effect of enzyme induction on the metabolism of bis(2-methoxyethyl)ether (diglyme) was studied in rats. Male Sprague-Dawley rats were administered 5.1 mmol/kg diglyme or 0.1% phenobarbital in their drinking water for 22 days. Other rats were pretreated with 5.1 mmol/kg diglyme or 0.1% phenobarbital administered in their drinking water for 22 days, and then given a single oral dose of 5.1 mmol/kg (14)C labeled diglyme. Urine samples were collected at 6 to 96 hours post dosing and analyzed for diglyme metabolites. Phenobarbital and diglyme caused significant decreases in hexobarbital sleeping time, phenobarbital showing the greater effect. Pretreatment with phenobarbital or diglyme did not significantly affect cumulative excretion of (14)C activity. Cumulative excretion of methoxyacetic acid, a minor metabolite, was significantly increased by both phenobarbital and diglyme, phenobarbital showing the greater effect. /It was concluded/ that pretreating rats with diglyme or phenobarbital increases the extent of cleavage of the ether bond in diglyme, forming 2-methoxyethanol, a precursor of methoxyacetic acid, a putative reproductive toxicant.|The testicular toxicity of bis(2-methoxyethyl)ether (diglyme) was studied in rats. Male Sprague-Dawley-rats were given 0.051, or 5.1 mmol/kg (14)C labeled diglyme orally. Approximately 86 to 90% of each dose was excreted in the urine over 96 hours. Less than 5% of the doses was excreted in the feces. Only trace amounts of radiolabel were found in the expired air as volatile organic compounds. The principal urinary metabolites were (2-methoxyethoxy)acetic acid and methoxyacetic acid which accounted for around 70 and 6% of the doses, respectively. Smaller amounts of N-(methoxyacetyl)glycine, diglycolic acid, 2-methoxyethanol, and 2-(2-methoxyethoxy)ethanol were found. Only unchanged diglyme was found in the volatile organic fraction of the expired air. ... Diglyme metabolism proceeds primarily through an O-demethylation pathway, followed by oxidation to (2-methoxyethoxy)acetic acid. The lack of toxicity of 2-(2-methoxyethoxy)ethanol and (2-methoxyethoxy)acetic acid suggests that the testicular toxicity of diglyme may be due to methoxyacetic acid, a minor metabolite.|The metabolism of ... bis(2-methoxyethyl)ether (diglyme) was studied in isolated rat hepatocytes and in the intact rat. Male Sprague-Dawley rats (190-220 g) were used in both studies. Hepatocytes, isolated by a two-step in situ collagenase perfusion of the liver, were cultured as monolayers and incubated with [14C]diglyme at 1, 10, 30, and 50 uM for up to 48 hr. For the in vivo study, rats were given single oral doses of [14C]diglyme at 5.1 mmol/kg bw, and urine was collected for up to 96 hr. Radioactive compounds in the culture medium or in the urine were separated by high performance liquid chromatography and quantified with an in-line radioactivity monitor. Metabolites were identified by comparison of their chromatographic retention times and their mass spectra with those of authentic compounds. The principal metabolite from hepatocytes and in the urine was (2-methoxyethoxy)acetic acid (MEAA). This metabolite accounted for approximately 36% of the radioactivity in the 48-hr culture medium and about 67% of the administered dose in the 48-hr urine. Other prominent metabolites common to both systems included 2-(2-methoxyethoxy)ethanol, methoxyacetic acid (MAA), 2-methoxyethanol, and diglycolic acid. The diglyme metabolite profiles from urine and from hepatocytes were qualitatively similar, demonstrating that, in the rat, hepatocytes serve as a good model system for predicting the urinary metabolites of diglyme. Moreover, MEAA was shown to be the metabolite best suited for use as a short-term biological marker of exposure to diglyme.|An embryotoxic oral dose of bis(2-methoxyethyl) ether (DGDME), 3.73 mmol/kg bw (500 mg/kg), administered on the 11th day of gestation to pregnant CD-1 mice was metabolized predominantly by O-demethylation to 2-(2-methoxyethoxy)ethanol with subsequent oxidation to (2-methoxyethoxy)acetic acid. Urinary excretion of this metabolite over 48 hr amounted to 63 +/- 2% of the dose. A smaller percentage of the administered dose was metabolized at the central ether linkage to produce 2-methoxyethanol, which was further metabolized by alcohol dehydrogenase to methoxyacetic acid. Urinary excretion of methoxyacetic acid, a potent developmental toxicant, amounted to 28 +/- 1% of the administered dose by 48 hr and was the second most prominent urinary metabolite. Unchanged DGDME and methoxyacetic acid were detected in the embryonic tissues from these animals, and embryos harvested after the initial 6-hr period showed detectable amounts of only methoxyacetic acid. The average amount of methoxyacetic acid per embryo was calculated to be 1.5 +/- 1.0 umol (5.9 mmol/kg bw) at the 6-hr termination time. This finding suggests that the reported teratogenic effects of DGDME are due to methoxyacetic acid formed, either in the fetus or by hepatic metabolism in the dam with subsequent distribution to the embryonic tissue. ...|For more Metabolism/Metabolites (Complete) data for DIETHYLENE GLYCOL DIMETHYL ETHER (6 total), please visit the HSDB record page.

The /diglyme/ metabolite 2-methoxyacetic acid has shown evidence of accumulation in animals and humans. In humans, its half-life was calculated as 77.1 hr.

INGESTION (severe cases): nausea, vomiting, abdominal cramps, weakness progressing to coma. (USCG, 1999)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Fresh air, rest.

Remove contaminated clothes. Rinse skin with plenty of water or shower.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

/GENOTOXICITY/ 2-Methoxyethanol and bis(2-methoxyethyl)ether were subjected to the ... unscheduled DNA synthesis (UDS) assay in human embryo fibroblasts ... UDS in fibroblasts were not increased by either compound.|/OTHER TOXICITY INFORMATION/ The ethers of diethylene glycol are lower in toxicity than the ethers of ethylene glycol, but they have many similar characteristics. /Diethylene glycol ethers/|/EPIDEMIOLOGY STUDIES/ Ethylene glycol ethers (EGEs) including diglyme are used in the manufacture of semiconductors. Epidemiological studies of semiconductor populations evaluated potential adverse reproductive outcomes. ... In each of these studies, workers were exposed to mixtures including diglyme but not to diglyme alone. ... Exposure to EGEs was determined using questionnaires from subjects about the work performed and an assessment of the work environment by industrial hygienists, but no measurements of personal or area exposures were made. Workers in the fabrication area were considered exposed to EGEs. For the retrospective study, information on pregnancy outcomes and potential confounders (age, smoking, ethnicity, education, income, year of pregnancy, and stress) was obtained through a comprehensive interviewer-administered interview of female employees. The prospective study of early fetal loss and fecundity (probability of conception per menstrual cycle) was conducted in a subset of female employees from five plants. Daily diaries and measurements of daily urinary human chorionic gonadotrophin (hCG) levels for 6 months were collected in addition to the comprehensive interview. Of the 891 medically verified pregnancies identified for the retrospective study, 774 (86.9%) were live births, 113 (12.7%) were spontaneous abortions, and 4 (0.4%) were stillbirths. The overall unadjusted relative risk (RR) for spontaneous abortions was 1.45 (95% confidence interval [CI] = 1.02-2.05) and changed little after adjusting for confounders (adjusted RR =1.43; 95% CI = 0.95-2.09). When stratified by work group, the risk of spontaneous abortion was statistically significantly increased for female workers in the photolithography group (RR = 1.67; 95% CI = 1.04-2.55) and in the etching group (RR = 2.08; 95% CI = 1.27-3.19). For women working with higher levels of EGE only in masking, the risk for spontaneous abortion was increased 3-fold (RR = 3.38; 95% CI = 1.61-5.73). In the prospective study, no statistically significant differences were detected in the overall rate of spontaneous abortions between fabrication and non-fabrication workers or when pregnancy outcomes were examined by work group. However, the ability to conceive was lower among female workers exposed to EGEs (fertility rate [FR] = 0.37; 95% CI = 0.11-1.19). /Ethylene glycol ethers/|/EPIDEMIOLOGY STUDIES/ Painters exposed to the solvent 2-methoxyethanol, which is also a metabolite of diglyme, were found to have an increased prevalence of oligospermia and azoospermia. ... Semen samples from 73 painters and 40 controls from a shipyard were analysed. The painters were exposed by inhalation to 0-17.7 mg 2-methoxyethanol/ cu m (mean 2.6 mg/cu m) and to 0-80.5 mg 2-ethoxyethanol (= ethylene glycol monoethyl ether)/cu m (mean 9.9 mg/cu m). Skin contact with 2-methoxyethanol and 2-ethoxyethanol was also considered possible. Exposure to numerous other substances, including organic solvents and metals, was also known to occur. While no effects were seen in hormone levels or in sperm viability, motility, and morphology, the prevalence of those with oligospermia differed between the groups. The proportion of men with a sperm density 100 million/cm3 was higher in the exposed group than in the unexposed group (33% vs. 20%; P = 0.20). The proportion of those with oligospermia among painters who did not smoke compared with controls was 36% vs. 16% (P = 0.05). The proportion of those with oligospermia was similar between painters and controls who smoked (30% vs. 38%; P = 0.49). The proportion of painters with azoospermia was 5% compared with 0% in the controls. /2-Methoxyethanol/

bis(2-methoxyethyl)ether

The substance can be absorbed into the body by inhalation of its vapour, by ingestion and through the skin.

Cough. Shortness of breath.

MAY BE ABSORBED! Redness.

Redness. Pain.

Grade: Technical

All other chemical product and preparation manufacturing|Ethane, 1,1'-oxybis[2-methoxy-: ACTIVE|S - indicates a substance that is identified in a final Significant New Use Rule.|Diglyme can be effectively used as an odor-attractant solvent without reducing the attractiveness of the chemical additive, eg, decanoic acid, trimethylammonium decanoate, and trimethylamine. Odorants dissolved in diglyme can be added to aqueous solutions, such as coyote urine. Also, diglyme has a low freezing point so its use as an odor solvent increases the temperature range in which an odor can be effectively used.

Gas chromatography is likely to be the analytical method for final analysis. Infrared absorption is sometimes used. /Glycol ethers/