Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Endpoint summary
Administrative data
Description of key information
Several repeated dose studies with diethylen glycol dimethylether as well as read-across approaches with respective metabolites have been performed.
All obtained effect concentrations or levels are liste:
Oral (read across to 2-Methoxyethanol, a metabolite of Diethylene glycol dimethyl ether):
NOAEL (14 days, drinking water study, male mouse): 200 mg/kg bw/d
NOAEL (14 days, drinking water study, female mouse): 600 mg/kg bw/d
NOAEL (13 weeks, drinking water study, male/female mouse): < 2000 ppm
LOAEL (14 days, drinking water study, male rat): 200 mg/kg bw/d
LOAEL (14 days, drinking water study, female rat): 200 mg/kg bw/d
NOAEL (13 weeks, drinking water study, male rat): < 750 ppm
Inhalation:
NOAEC (2 weeks, 6h/d, nose only, male rat): 30 ppm (key study)
NOAEC (3 weeks, 5 d/w, 6h/d, whole body, male/female rat): 200 ppm (corresponding 318.4 mg/kg bw/d)
NOAEC (2 weeks, 5 d/w, 6h/d, nose only, female rat): 370 ppm (corresponding to 589 mg/kg bw/d)
LOAEC (2 weeks, 5 d/w, 6h/d, nose only, male rat): 110 ppm (corresponding to 175.1 mg/kg bw/d)
NOAEC (5 days, 7h/d, whole body, male mouse): 250 ppm
NOAEC (2 weeks, 6h/d, nose only, male rat): < 110 ppm (corresponding to 175.1 mg/kg bw/d)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- subacute
- Quality of whole database:
- No repeated dose toxicity study with oral application have been performed with diethylene glycol dimethyl ether, but sufficient information after inhalation is available.
Additionally, data of the main toxic metabolite, 2-methoxyethanol, is available after oral dose administration. Here, a NOAEL of 200 mg/kg bw was observed.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEC
- 110 ppm
- Study duration:
- subacute
- Species:
- rat
- System:
- male reproductive system
- Organ:
- testes
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A 15 day (3 weeks) inhalation toxicity study was performed in rats. The animals were exposed to a Diethylene glycol dimethyl ether atmosphere of 200 ppm and 600 ppm. All animals survived and no clinical signs were noted at any dose level. Body weight gain of the rats at 200 ppm exposure (corresponding 318.4 mg/kg bw/d) was unaffected. The body weight of the rats of the 600 ppm dose group was irregular. There were no changes in haematology and urinalysis noted at any dose level.At 600 ppm the thymus was atrophied.
To assess the inhalation toxicity of Diglyme, groups of 20 male and 10 female rats were exposed by nose-only inhalation 6 hours/day, 5 days/week for 2 weeks to either 0 (control), 110, 370 or 1100 ppm Diglyme. 2-Methoxyethanol was applied as positive control. Rats were sacrificed immediately following exposure, after a 14-day recovery period, or after 42 and 84 days of recovery (males only). Parameters investigated included in-life observations and body weights, clinical pathology, and histopathology with organ weights. Exposure to Diglyme produced a variety of concentration-related changes. The most striking effect produced in all test groups was cellular injury involving the testes, seminal vesicles, epididymides and prostate. Although these effects were more severe at the higher concentrations tested, partial or complete recovery was seen by 84 days post-exposure. Changes in the haematopoetic system occurred in both sexes and involved the bone marrow, spleen, thymus, leucocytes and erythrocytes. The testicular effects of Diglyme were somewhat less pronounced than those seen with 2-Methoxyethanol. The NOEC for repeated inhalation exposure to Diglyme in female rats is 370 ppm (corresponding to 589 mg/kg bw/d). For males, the NOAEC was derived at 110 ppm (corresponding to 175.1 mg/kg bw/d).
A sperm abnormality test was performed with male mice. The animals were exposed to 0, 250 and 1000 ppm Diglyme for 7 h/d on 5 consecutive days. Sperm head abnormalites were increased in the high dose group leading to a NOEC of 250 ppm.
Male rats were exposed to 0, 110, 370, or 1100 ppm Bis(2-methoxyethyl)ether (Diglyme) 6 h/d, 5 d/week for 2 weeks. Rats were killed after 10 days of exposure and 14, 42, or 84 days post-exposure (PE), respectively. At 110 ppm, spermatocytes in pachytene and meiotic division at spermatogenic stages XII-XIV were mainly affected. At 370 ppm, affected germ cells were similar to those seen at 110 ppm, but round spermatids at spermatogenic stage I-VIII were also affected. The testes regained normal spermatogenesis by 84 days PE. At 1100 ppm, marked testicular atrophy was found affecting all spermatogenic stages. Damaged seminiferous tubules were lined with regenerating pachytene spermatocytes at 14 days PE and with spermatocytes and round spermatids after 42 days PE. Most but not all testes in rats exposed to 1100 ppm Diglyme had normal morphology after 84 days PE.
Since there is a strong evidence in literature that to 2-Methoxyethanol is a metabolite of Diethylene glycol dimethyl ether a read across to the 2 and 13-week drinking water study with 2-Methoxyethanol in rats and mice might be justified to estimate possible systemic effects of the glycol ether via oral route.
In summary, the major target organs for toxicity of 2-Methoxyethanol were testes in males (decrease in testicular and epididymal weight) and the haematopoetic system (lymphoid depletion) in both species. These effects were also observed via the inhalatory route.
Repeated dose toxicity: inhalation - systemic effects (target organ) urogenital: testes
Justification for classification or non-classification
Since no severe changes in pathology and histopathology of organs occurred in inhalation studies in rats and mice exposed to the test substance at a concentration up to 370 ppm (corresponding to 589 mg/kg bw/d; changes in male reproductive organs) and thymus atrophy was observed at dose levels of 600 ppm (corresponding to 955 mg/kg bw/d), Diethylene glycol dimethyl ether does not have to be classified regarding systemic and target organ toxicity after repeated exposure according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). However, adverse effects were observed in testes at doses of 110 ppm.
It can reasonably be deduced that the only severe effects caused by Diethylene glycol dimethyl ether are restricted to the male reproductive system (reduced testes weight, changes in seminiferous epithelium and spermatogenesis etc.) and the fetal development/viability. The substance is already classified accordingly (Cat 1B, H360FD – May damage fertility or the unborn child). No other severe systemic effects were observed after repeated applications to test animals. Furthermore the substance is found to be not irritating and it is unlikely that higher amounts than tested in the repeated dose toxicity study will be systemically available via the skin barrier. Therefore, toxicity testing via dermal route is not scientifically necessary.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.