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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 271-880-3 | CAS number: 68610-90-2
- 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:
- other: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 15 Sep - 16 Oct 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
- Reference Type:
- secondary source
- Title:
- Diesters Category of the Aliphatic Esters Chemicals (Test Plan and Robust Summaries for Substances in the HPV Test Plan)
- Author:
- US-EPA (American Chemistry Council's Aliphatic Esters Panel)
- Year:
- 2 010
- Bibliographic source:
- High Production Volume (HPV) Chemical Challenge Program (201-16837A and 201-16837B)
- Reference Type:
- secondary source
- Title:
- Bis(2-ethylhexyl)adipate (DEHA) CAS N°: 103-23-1
- Author:
- OECD
- Year:
- 2 000
- Bibliographic source:
- SIDS Initial Assessment Report for SIAM 10; Tokyo, Japan, 15-17 March 2000
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Bis(2-ethylhexyl) adipate
- EC Number:
- 203-090-1
- EC Name:
- Bis(2-ethylhexyl) adipate
- Cas Number:
- 103-23-1
- Molecular formula:
- C22H42O4
- IUPAC Name:
- bis(2-ethylhexyl) adipate
- Details on test material:
- - Name of test material (as cited in study report): Di(2-Ethylhexyl) Adipate
- Supplier: ICI France, Department Baleycourt
- Physical state: colourless liquid
- Batch: Y02259/003/003-4
- Analytical purity: 99.2 % w/w
- Impurities (identity and concentrations): Phthalate (as DOP) 0.08 % w/w
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Alpk:APfSD (Wistar derived)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF colony maintained at the Animal Breeding Unit, ICI Pharmaceuticals, Alderley Park, Cheshire, UK.
- Age at study initiation: 12 weeks.
- Weight at study initiation: 218-278 g.
- Housing: individually in stainless steel cages with absorbent paper over collecting trays.
- Diet: CTI diet, Special Diets Services Ltd., Essex, UK.
- Water: ad libitum.
ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 24 °C.
- Humidity: 44 - 70 %.
- Air changes: 12 per hr.
- Photoperiod: 12 hrs dark /12 hrs light
IN-LIFE DATES: 15 Sept - 16 Oct 1987.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: the experimental diets were prepared in 30 kg batches from premixes.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chemical stability was observed at 300 ppm up to at least 32 days. This interval was in excess of the maximum period of use of the first batch of diet (21 days from preparation). The achieved concentration was within 8 % of target and the doses received by the test groups were approximately 28, 170 and 1080 mg/kg bw/day.
- Details on mating procedure:
- - Impregnation procedure: cohoused.
- Length of cohabitation: overnight.
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy.
Successfully mated females were delivered to the experimental unit.
A total of 96 mated females was supplied over a two week period. - Duration of treatment / exposure:
- days 1 - 22 of gestation.
- Frequency of treatment:
- Continuous feeding
- Duration of test:
- 22 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 28 mg/kg bw/day
- Remarks:
- approximately received doses (as given in study report)
- Dose / conc.:
- 170 mg/kg bw/day
- Remarks:
- approximately received doses (as given in study report)
- Dose / conc.:
- 1 080 mg/kg bw/day
- Remarks:
- approximately received doses (as given in study report)
- Dose / conc.:
- 300 ppm (nominal)
- Remarks:
- nominal in diet
- Dose / conc.:
- 1 800 ppm (nominal)
- Remarks:
- nominal in diet
- Dose / conc.:
- 12 000 ppm (nominal)
- Remarks:
- nominal in diet
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, plain diet
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: yes
- Time schedule: on arrival and daily
BODY WEIGHT: yes
- Time schedule for examinations: daily during days 1 - 22 of gestation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: yes.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: yes.
POST-MORTEM EXAMINATIONS: yes
- Sacrifice on gestation day 22
- Organs examined: uterus, ovaries, liver, spleen, kidney, stomach, rectum, abdominal cavity, pelvic cavity, - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: yes.
- Number of corpora lutea: yes, in each ovary.
- Number of implantations: yes.
- Number of early resorptions: yes (early intra-uterine deaths).
- Number of late resorptions: yes (late intra-uterine deaths). - Fetal examinations:
- - External examinations and cleft palate: yes, each foetus.
- Soft tissue examinations: yes, all.
- Skeletal examinations: yes, all.
- Head examinations: yes, the head of each foetus was cut along the fronto-parietal suture line and the brain was examined for macroscopic abnormalities.
- Other: each foetus was weighed and individually identified within the litter by means of a cardboard tag. After weighing the foetuses were killed with an intra-cardiac injection of pentobarbitone. - Statistics:
- Analysis of variance, Student's t-test, Fisher's Exact Test
- Indices:
- - Pre-implantation loss (No. of corpora lutea / No. of implantations)
- Post implantation loss (No. of implantations / No. of live foetuses) - Historical control data:
- Yes, data on variants and frequency of occurence in rats of this strain were given.
Defects like bipartite 5th sternebrae, slightly dilated ureters and kinked ureters were seen in historical controls of this strain.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- MATERNAL TOXIC EFFECTS: yes
DETAILS ON MATERNAL TOXIC EFFECTS
At 12000 ppm a small but statistically significant reduction in maternal bodyweight gain was observed.
There was also a small but statistically significant reduction in food consumption at this dose level from days 2-18 inclusive of gestation.
There was no evidence of maternal toxicity at 300 or 1800 ppm.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 170 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- equivalent to 1800 ppm in diet.
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 1 080 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- equivalent to 12000 ppm in diet.
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- EMBRYOTOXIC / TERATOGENIC EFFECTS: yes. (non-adverse)
DETAILS ON EMBRYOTOXIC / TERATOGENIC EFFECTS:
There was no effect at any dose on fetal weight, litter weight, gravid uterus weight, numbers of intra-uterine deaths or numbers of external abnormalities. At 12000 ppm there was a minimal increase of pre-implantation loss with an associated decrease in litter size.
Six major abnormalities (in five fetuses) were seen in the treated groups and eight in the control group (of which seven consisted of multiple minor skull defects in one litter). There was no evidence that the type or distribution of these abnormalities was related to treatment with the test substance.
Overall, minor skeletal defects were increased in a dose-related manner at 1800 and 12000 ppm of the test substance, while skeletal variants (as a percentage of foetuses affected) were increased at the top dose only. These findings indicated slightly poorer ossification at dose levels of 1800 and 12000 ppm, which were considered to be the result of slight fetotoxicity. However, the slightly poorer ossification is not considered as adverse effect.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 080 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- equivalent to 12000 ppm in diet.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Dose descriptor:
- LOEL
- Effect level:
- ca. 170 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- equivalent to 1800 ppm in diet.
- Sex:
- male/female
- Basis for effect level:
- other: delayed ossification
- Dose descriptor:
- NOEL
- Effect level:
- ca. 28 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- equivalent to 300 ppm in diet.
- Sex:
- male/female
- Basis for effect level:
- other: delayed ossification
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table: Foetal defects and variants - Intergroup comparison of foetal defects and variants
|
Dietary conc. of DEHA (ppm) |
|||
0 |
300 |
1800 |
12000 |
|
No. of litters examined |
24 |
23 |
24 |
23 |
External and visceral defects |
||||
No. of foetuses examined |
282 |
263 |
278 |
243 |
No. of foetuses showing major defects |
1 |
2 |
0 |
2 |
No. of foetuses showing minor defects only |
7 |
8 |
9 |
3 |
Variants |
||||
No. of foetuses showing variants |
69 |
69 |
81 |
78* |
Skeletal defects |
||||
No. of foetuses examined |
282 |
263 |
278 |
243 |
No. of foetuses showing major defects |
7 |
0 |
1 |
1 |
No. of foetuses showing minor defects only |
70 |
78 |
97** |
120** |
Variants |
||||
No. of foetuses showing variants |
270 |
257 |
268 |
243** |
Table: Summary of the type and incidence of major defects
|
Dietary conc. of DEHA (ppm) |
|||
0 |
300 |
1800 |
12000 |
|
External/Visceral |
||||
Situs inversus totalis |
0 |
0 |
0 |
1 |
Left adrenal, kidney and ureter absent |
1 |
0 |
0 |
0 |
Cysts attached to liver |
0 |
1 |
0 |
0 |
Small right kidney |
0 |
1 |
0 |
0 |
Umbilical hernia |
0 |
0 |
0 |
1 |
Skeletal |
||||
Skull: Multiple minor defects |
7 |
0 |
0 |
0 |
3rd and 7th ribs (left) not ossified |
0 |
0 |
0 |
1 |
1st rib (right) partially ossified |
0 |
0 |
1 |
0 |
There was no evidence that the test substance is teratogenic to the rat at any of the dose levels tested (up to 12000 ppm -approximately 1000 mg/kg/day). Administration of 12000 ppm DEHA resulted in slight maternal toxicity and slight foetotoxicity.
At 1800 ppm, there was no evidence of maternal toxicity although minimal foetotoxicity was observed. A dietary level of 300 ppm DEHA was a clear no-effect level for embryonic development.
Applicant's summary and conclusion
- Conclusions:
- NOAEL (maternal toxicity) = 170 mg/kg bw/day
LOAEL (maternal toxicity) = 1080 mg/kg bw/day
NOAEL (developmental toxicity) ≥ 1080 mg/kg bw/day
NOEL (developmental toxicity) = 28 mg/kg bw/day
LOEL (developmental toxicity) = 170 mg/lkg bw/day - Executive summary:
The effects of the analogue substance on mated female Alpk:APfSD (Wistar derived) rats were investigated during Days 1 to 22 of gestation in a prenatal developmental toxicity study according to OECD guideline 414. Groups of 24 females received the test substance at dietary concentrations of 300, 1800 and 12000 ppm, which approximately corresponded to dose levels of 28, 170 and 1080 mg/kg bw/day. A further group of 24 mated females received the plain diet and served as controls. On Day 22 of gestation, dams were sacrificed and maternal as well as foetal examinations were performed.
Maternal toxicity occurred at 12000 ppm and involved a small, but statistically significant decrease in body weight gain compared to controls. This effect was accompanied by slight, statistically significant reduction in food consumption between Days 2 to 18 of gestation. No treatment-related clinical signs were observed during the study and no adverse findings were noted at macroscopic examination of dams.
There was no effect at any dose level on fetal weight, litter weight, gravid uterus weight, numbers of intra-uterine deaths or numbers of external abnormalities. At 12000 ppm, a minimal increase of pre-implantation loss associated with a decrease in litter size was observed. Six major abnormalities (in five fetuses) were seen in the treated groups and eight in the control group (of which seven consisted of multiple minor skull defects in one litter). There was no evidence that the type or distribution of these abnormalities was related to test substance treatment. Overall, minor skeletal defects were increased in a dose-related manner at 1800 and 12000 ppm, while skeletal variants (as a percentage of fetuses affected) were increased at 12000 ppm only. These findings indicated slightly poorer ossification at dose levels of 1800 and 12000 ppm. However, the slightly poorer ossification is not considered as an adverse effect. There was no evidence at any dose level, that the test substance was teratogenic in rats.
Based on the results of the study, the NOEL for developmental toxicity in Alpk:APfSD (Wistar derived) rats was set at 300 ppm, which corresponded to approximately 28 mg/kg bw/day. The NOAEL for developmental toxicity in Alpk:APfSD (Wistar derived) rats was ≥ 12000 ppm, which is equivalent to ca. ≥ 1080 mg/kg bw/day. The NOAEL for maternal toxicity in Alpk:APfSD (Wistar derived) rats was 1800 ppm, which is equivalent to ca. 170 mg/kg bw/day
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.