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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 940-417-3 | CAS number: -
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Study period:
- 2011-06-06 to 2011-12-23
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Non GLP; equivalent to OECD 414 with deviation; scientifically well performed study. Rationale for grouping: structural similarity given by the presence of ”butyl-O-CH2CH2 -O-“ at terminal position; systemic exposure to 2-butoxyacetic acid and/or butoxyethoxyacetic acid as common mode of action; comparable toxicity profiles after prolonged exposure
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- 8 animals per group
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Regulation (EC) No. 440/2008, L 142, Annex Part B, May 30, 2008
- Deviations:
- yes
- Remarks:
- 8 animals per group
- Principles of method if other than guideline:
- The number of animals was 8 per group instead of 20.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Bis(2-butoxyethyl) ether
- EC Number:
- 204-001-9
- EC Name:
- Bis(2-butoxyethyl) ether
- Cas Number:
- 112-73-2
- Molecular formula:
- C12H26O3
- IUPAC Name:
- 1,1'-[oxybis(ethane-2,1-diyloxy)]dibutane
- Reference substance name:
- DEGDBE
- IUPAC Name:
- DEGDBE
- Test material form:
- gas under pressure: refrigerated liquefied gas
- Details on test material:
- Name: Diethyleneglycoldibutylether
CAS No.: 112-73-2
Chemical Name: Bis(2-butoxyethyl)ether
Active Components: 100%
Physical State: liquid
pH: 6, 5-7, 5 (25oC, 100 g/L i-propanol/ water 4:1)
Colour: Colourless
Storage: Room Temperature (RT)
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 11-12 weeks old
- Housing: Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- The animals were acclimatised for at least five days. After acclimatisation, females were paired with males as per the ratio of 1:2 (male to female). Females were paired for cohabitation in batches in order to regularize the number of animals for terminal sacrifice on particular day. The subsequent morning and the next morning onwards, the vaginal smear of female was checked to confirm the pregnancy. The day on which sperms were observed in the vaginal smear was considered as gestation day ‘0’. Mated females were assigned in an unbiased manner to the control and treatment groups ensuring that group mean body weights were comparable with each other.
- Duration of treatment / exposure:
- in females from the Gestation Day (GD) 5 to GD 19
- Frequency of treatment:
- daily
- Duration of test:
- On gestation day 20 caesarean section was performed
Doses / concentrations
- Remarks:
- Doses / Concentrations:
250, 500, 750 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 8 females per dose
- Control animals:
- yes
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once a day
- morbidity and mortality
DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:at least once a day
BODY WEIGHT:
- The sperm positive females were weighed on GD 0, 5, 8, 11, 14, 17 and 20.
- Males were not weighed in this study.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption of sperm positive females was measured on GD 5, 8, 11, 14, 17 and 20. The food consumption was presented for period 0-5, 5-8, 8-11, 11-14, 14-17, and 17-20.
- The food consumption was measured neither for males during the entire study nor for both male and females during the mating period.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- structural abnormalities or pathological changes
- uteri, gravid uterus with cervix, corpora lutea
- Males were sacrificed at any time after completion of the mating of all females without any observations - Ovaries and uterine content:
- The uterine contents were examined for embryonic or fetal deaths and the number of viable fetuses. The degree of resorption (late and early) was ascertained in order to help estimate the relative time of death of the conceptus.
The position /number of fetuses in each uterine horn were also be recorded. - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Mortality:
- no mortality
Clinical observation:
- salivation, moving the bedding, weight loss and piloerection at 500 and 750 mg/kg bw
Body weight development:
-significant body weight decrease between GD5 to 8 at 500 and 750 mg/kg bw
- significant body weight gain decrease from GD5 onwards at 500 and 750 mg/kg bw
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Prenatal data:
- inceased pre- and postimplantation loss at 500 and 750 mg/kg bw
- decreased number of live pubs at 500 and 750 mg/kg bw
- decreased mean litter weight at 750 mg/kg bw
Fetal external examination:
- no treatment related effect
Fetal visceral examination
- no treatment related effect.
Fetal skeletal examination:
- increased incidences of abnormality at 500 and 750 mg/kg bw
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Maternal toxicity: Table 1 - 3
Table 1: Summary of Clinical Observation (Number of animals affected) |
||||
Clinical Findings |
Control n=8 |
250 mg/kg bw n=8 |
500 mg/kg bw n=8 |
750 mg/kg bw n=10 |
Alopecia |
2 |
1 |
1 |
0 |
Aggressive behaviour |
1 |
0 |
0 |
0 |
Piloerection |
0 |
2 |
1 |
6 |
Injury |
0 |
1 |
0 |
0 |
Salivation |
0 |
1 |
4 |
9 |
Moving the bedding |
0 |
0 |
3 |
10 |
Increased spontaneous activity |
0 |
0 |
0 |
1 |
Weight loss |
0 |
0 |
0 |
2 |
Dehydration |
0 |
0 |
0 |
1 |
Reduced spontanoues activity |
0 |
0 |
0 |
1 |
Bloody urinigenital region |
0 |
0 |
0 |
1 |
Bloody urine |
0 |
0 |
0 |
1 |
Table 2: Summary of Gestation Body Weight [g] |
||||
Gestation Day |
Control
n=8 |
250 mg/kg bw n=8 |
500 mg/kg bw n=6 |
750 mg/kg bw n=10 |
0 |
222 ± 5 |
219 ± 12 |
215 ± 3 |
218 ± 8 |
5 |
235 ± 8 |
235 ± 17 |
233 ± 5 |
233 ± 10 |
8 |
242 ± 9 |
239 ± 17 |
231 ± 11 |
217 ± 15 |
11 |
253 ± 9 |
249 ± 14 |
243 ± 8 |
233 ± 14 |
14 |
267 ± 9 |
263 ± 16 |
254 ± 12 |
249 ± 13 |
17 |
292 ± 8 |
284 ± 16 |
274 ± 16 |
271 ± 16 |
20 |
321 ± 10 |
318 ± 18 |
300 ± 25 |
291 ± 30 |
Table 3: Summary of Gestation Body Weight Gain [g] |
||||
Gestation Day |
Control
n=8 |
250 mg/kg bw n=8 |
500 mg/kg bw n=6 |
750 mg/kg bw n=10 |
0 to 20 |
99 ± 9 |
99 ± 11 |
85 ± 25 |
73 ± 28 |
0 to 5 |
13 ± 4 |
16 ± 6 |
18 ± 4 |
16 ± 5 |
5 to 8 |
7 ± 4 |
4 ± 5 |
-2 ± 8 |
-16 ± 9 |
8 to 11 |
11 ± 2 |
10 ± 4 |
12 ± 5 |
16 ± 4 |
11 to 14 |
14 ± 4 |
14 ± 3 |
11 ± 5 |
16 ± 6 |
14 to 17 |
25 ± 5 |
21 ± 4 |
20 ± 6 |
23 ± 8 |
17 to 20 |
29 ± 7 |
35 ± 5 |
26 ± 9 |
19 ± 15 |
Prenatal Data: Table 4
Table 4: Summary of Prenatal Data |
||||
Control
n=8 |
250 mg/kg bw n=8 |
500 mg/kg bw n=6 |
750 mg/kg bw n=10 |
|
Terminal Body Weight [g] |
320 ± 10 |
318 ± 18 |
300 ± 25 |
291 ± 30 |
Uterus Weight[g] |
67 ± 7 |
64 ± 8 |
43 ± 25 |
57 ± 20 |
Adjusted Weight [g] |
254 ± 12 |
254 ± 16 |
257 ± 20 |
233 ± 16 |
Corpora Lutea |
13.88 ± 1.25 |
13.50 ± 1.07 |
14.33 ± 1.21 |
13.70 ± 0.82 |
Implantations |
12.75 ± 1.58 |
12.63 ± 1.06 |
10.33 ± 5.35 |
12.90 ± 0.99 |
Live Fetuses |
12.38 ± 1.85 |
12.13 ±1.46 |
9.17 ± 4.88 |
11.00 ± 3.94 |
Dead Fetuse |
0 |
0 |
0 |
0 |
Total Resorption |
0.38 ± 0.74 |
0.50 ± 0.76 |
1.17 ± 1.47 |
1.90 ± 3.93 |
Pre Implantation Loss [%] |
7.93 ± 9.71 |
6.13 ± 8.79 |
28.31 ± 36.62 |
5.79 ± 5.70 |
Post Implantation Loss [%] |
3.04 ± 6.13 |
4.09 ± 6.24 |
11.18 ± 11.88 |
14.51 ± 30.25 |
Litter Data: Table 5
Table 5: Summary of Litter Weight Data |
||||
Control n=8 |
250 mg/kg bw n=8 |
500 mg/kg bw n=6 |
750 mg/kg bw n=10 |
|
Litter Mean Weight [g] |
3.30 ± 0.22 |
3.22 ± 0.14 |
3.46 ± 0.38 |
2.75 ± 1.04 |
Total Litter Weight[g] |
40.59 ± 4.13 |
39.05 ± 5.00 |
30.38 ± 14.71 |
33.57 ± 12.81 |
Table 6: Findings in Skeletal Examination; findings only with clearly increased incidences given |
|||||||||||||
Control
n = 49 |
250 mg/kg bw n=49 |
500 mg/kg bw n = 29 |
750 mg/kg bw n=51 |
||||||||||
A |
B |
C |
A |
B |
C |
A |
B |
C |
A |
B |
C |
||
IO-4thmetacarpal, both |
0 |
0 |
0 |
3 |
6.1 |
2 |
6 |
20.7 |
3 |
19 |
37.3 |
8 |
|
IO-4thsternebrum |
15 |
30.6 |
1 |
19 |
38.8 |
7 |
8 |
27.6 |
4 |
39 |
76.5 |
8 |
|
IO-Frontal |
0 |
0 |
0 |
4 |
8.2 |
4 |
9 |
31.0 |
3 |
19 |
37.3 |
7 |
|
IO-Hyoid |
0 |
0 |
0 |
1 |
2.0 |
1 |
7 |
24.1 |
2 |
9 |
17.6 |
5 |
|
IO-Temporal, both |
1 |
2.0 |
1 |
1 |
2.0 |
1 |
9 |
31.0 |
3 |
14 |
27.5 |
5 |
|
IO-Xiphoid |
10 |
20.4 |
7 |
13 |
26.5 |
5 |
6 |
20.7 |
3 |
25 |
49.0 |
8 |
|
Rudimentary rib-14th, both |
3 |
6.1 |
4 |
2 |
4.1 |
2 |
6 |
20.7 |
5 |
2 |
3.9 |
2 |
|
Rudimentary rib-14th, left |
2 |
4.1 |
2 |
2 |
4.1 |
1 |
3 |
10.3 |
3 |
4 |
7.8 |
4 |
|
Rudientary rib-14th, right |
1 |
2.0 |
1 |
3 |
6.1 |
2 |
6 |
20.7 |
5 |
6 |
11.8 |
6 |
|
Waxy ribs |
1 |
2.0 |
1 |
4 |
8.2 |
4 |
3 |
10.3 |
3 |
20 |
39.2 |
8 |
|
A: Total number of incidences for particular abnormality
B: % Incidence
C: Number of litters in group having at least one fetus with the particular abnormality
Applicant's summary and conclusion
- Conclusions:
- The developmental toxicity of DEGDBE was investigated according to OECD 414 with deviations of using limited number of animals. DEGDBE induced at 500 mg/kg bw and above reduced body weight and increased pre and post implantation loss, reduced mean litter weight and abnormalities/variations upon skeletal examination. At 250 mg/kg bw no maternal toxicity and no fetal toxicity was found.
- Executive summary:
The developmental toxicity of the registration substance was assessed based on the data of the read-across supporting substance diethylenglycoldibutylether (DEGDBE).
The developmental toxicity of DEGDBE was investigated according to OECD 414 with deviations of using limited number of animals. Each eight pregnant rats were treated with DEGDBE per gavage at doses of 0. 250, 500, 750 mg/kg bw. The initial high dose level was 1000 mg/kg bw, but due to the severe sufferings of treated animals the dose level was adjusted to 750 mg/kg bw.
DEGDBE at 500 and 750 mg/kg bw induced transient body weight loss (gestation day 5 -8, ), reduced body weight gain, increased pre- and post-implantation loss, reduced live fetuses, reduced litter mean weight and increased incidences of findings upon skeletal examinations. No developmental toxicity in absence of maternal toxicity could be found. The NOAEL of 250 mg/kg bw was determined for maternal and fetal toxicity.
Based on the read-across approach, no developmental toxicity is predicted for the registration substance.
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.