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EC number: 203-924-4 | CAS number: 111-96-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- received: 22 July 1986
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-guideline study following scientifically sound study design (mechanistic study) with restricted reporting.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Pregnant CD-1 mice were treated with a single dose of Diethylene glycol dimethyl ether on gestation day 11. Fetuses were collected on gestation day 18 and examined for gross external malformations.
- GLP compliance:
- not specified
- Type of method:
- in vivo
Test material
- Reference substance name:
- Bis(2-methoxyethyl) ether
- EC Number:
- 203-924-4
- EC Name:
- Bis(2-methoxyethyl) ether
- Cas Number:
- 111-96-6
- Molecular formula:
- C6H14O3
- IUPAC Name:
- 1-methoxy-2-(2-methoxyethoxy)ethane
- Reference substance name:
- Diglyme
- IUPAC Name:
- Diglyme
- Reference substance name:
- Diethylene glycol dimethyl ether
- IUPAC Name:
- Diethylene glycol dimethyl ether
- Details on test material:
- Purchased from Aldrich Chemical Company (Milwaukee, WI, USA)
Lot: 0115LE
Purity: >=99%
Constituent 1
Constituent 2
Constituent 3
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Time-mated female CD-1 mice were obtained from Charles River Laboratories (Kingston, NY, USA). Mice were shipped on gestation day 4 (day of plug = 0) and received on gestation day 5. Throughout the experiment, mice were housed in groups of five in solid-bottom cages with absorbent bedding and with free access to food and water. Light was provided on a 12 h light-dark cycle.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Treatments were administered by gavage in a standard volume of 10 mL/kg bw. On gestation day 11 control mice were dosed with distilled water as the vehicle, and experimental mice received Diethylene glycol dimethyl ether in distilled water of 4 mmol/kg bw (537 mg/kg bw). on gestation day 18 mice were killed by carbon dioxide aphyxiation. Gross maternal body weights and gravid uterus weights were recorded. Live and dead implants were counted, and live fetuses were removed, weighed and preserved in 70% Ethanol for subsequent staining with Alizarin red. Stained specimens were examined for paw malformations.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Duration of treatment / exposure:
- single exposure
- Frequency of treatment:
- single application
- Duration of test:
- 18 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
537 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- control: 13
treatment: 17 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Please refer to "Details on exposure"
- Statistics:
- Adjusted maternal body weight (body weight at termination minus gravid uterus weight), fetal body weight (average weights per litter), and numbers of live and dead implants per litter and concurrent control group were analysed by analysis of variance. The incidence of fetal malformations (the number of litters with one or more fetuses affected) was evaluated by one-sided Fisher's exact test. All analyses werecarried out by means of the Statistical Analysis System (SAS Institute Inc., NC, USA).
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- (maternal)
- Effect level:
- 537 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: no effects observed
- Dose descriptor:
- NOAEL
- Remarks:
- (developmental)
- Effect level:
- < 537 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: increased incidence of paw defects
Observed effects
Any other information on results incl. tables
Litters were collected from control and treated group in the early afternoon of gestation day 18. Two dams in the control group and one in the treatment group delivered all or part of their litters before sacrifice. Pups from those litters were examined for external malformations and paw defects. There was no evidence of cannibalization in any of these litters.
At a dose of 4 mmol/kg bw (537 mg/kg bw) Diethylene glycol dimethyl ether did not affect adjusted maternal body weight. Similarly, it was not associated with a reduced number of live fetuses or an increased number of dead implantation site.
Gross fetal malformations seen at necropsy included open eye and exencephaly, but these did not appear to be treatment related. Paw defects were rarely seen in control fetuses but occured with significantly increased frequency in litters of mice treated with the test item. Diethylene glycol dimethyl ether affected 39.7% per litter.
Polydactyly was a rare observation. Syndactyly was the most common digital defect observed, appearing with significantly increased frequency in hindpaws of the Diethylene glycol dimethyl ether treated litters. Short digit were not seen in any of the 61 control litters (637 fetuses) but occured in both fore- and hindpaws of the treated litters. The frequency was significantly increased in hindpawsof Diethylene glycol dimthyl ether treated litters. Oligodactyly was not observed in any control litter, but appeared at a significant frequency in hindpaws of dosed litters.
Table 1: Litter data at 537 mg Diethylene glycol dimethyl ether/kg bw
|
Control |
Diethylene glycol dimethyl |
|
|
|
Maternal body weight1 N= |
33.9±3.1 |
33.6±2.0 17 |
Implants per litter |
|
|
Live fetuses |
10.9±4.1 |
11.5±2.0 |
Dead + resorbed |
0.3±0.5 13 |
0.1±0.2 |
Fetal body weight2 |
1.43±0.15 |
1.40±0.20 |
|
|
|
1 Gravid uterus not weighed
2 Mean of litter means
Table 2: Paw malformations by type and location at
537 mg Diethylene glycol dimethyl ether /kg bw
|
Control |
Diethylene glycol dimethyl |
|
|
|
No. examined-litters (fetuses) |
15(164) |
18 (201) |
|
|
|
Paw defects- litters (fetuses) |
|
|
|
|
|
Polydactyly |
0
0 |
0
0 |
Syndactyly |
0
0 |
2 (3) 11.1 (1.4) 13***(62) 72.2 (30.9) |
Short Digits |
0
0 |
2 (2) 11.1 (0.8) 10***(21) 55.6 (10.4) |
Oligodaytyly |
0
0 |
3 (4) 16.7 (1.8) 7**(7) 38.9 (3.2) |
Total |
0
0 |
5*(10) 27.8 (4.4) 13***(77) 72.2 (38.0) |
|
|
|
1 % of fetuses = average % per litter
* p<0.05
** p<0.01
*** p<0.001
Applicant's summary and conclusion
- Conclusions:
- The application of 537 mg/kg bw Diethylene glycol dimethyl ether did not result in maternal effects but led to an increased incidence in paw defects in the fetuses.
- Executive summary:
Pregnant CD-1 mice were treated with a single dose of Diethylene glycol dimethyl ether on gestation day 11. Fetuses were collected on gestation day 18 and examined for gross external malformations. This application did not result in maternal effects but led to an increased incidence in paw defects in the fetuses.
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