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EC number: 230-072-0 | CAS number: 6938-94-9
- 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:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from a publication.
Data source
Reference
- Reference Type:
- publication
- Title:
- Embryonic-Fetal Toxicity and Teratogenic Effects of Adipic Acid Esters in Rats
- Author:
- Singh, A .R ., Lawrence, W .H ., and Autian, J
- Year:
- 1 973
- Bibliographic source:
- Journal of Pharmaceutical Sciences. VoL 62, No. 10 October 1973:1596-1600
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Embryonic-fetal toxicity and teratogenic study of the test chemical in rats
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Diisopropyl adipate
- EC Number:
- 230-072-0
- EC Name:
- Diisopropyl adipate
- Cas Number:
- 6938-94-9
- Molecular formula:
- C12H22O4
- IUPAC Name:
- 1,6-bis(propan-2-yl) hexanedioate
- Details on test material:
- - Name of test material (as cited in study report):dipropyl adipate
- Molecular formula (if other than submission substance):C12H22O4
- Molecular weight (if other than submission substance): 230.302 g/mol
- Substance type:organic
- Physical state: liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sprague-Dawley Inc., Madison, WI
- Age at study initiation: No data available
- Weight at study initiation: 175-225 g
- Fasting period before study:No data available
- Housing: Females were housed individually after confirmed pregnancy.
- Diet (e.g. ad libitum): Purina laboratory chow, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: Female rats were selected for experimentation only after observation of at least two complete 4- or 5-day estrus cycles.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-27°C
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No Data Available
- Details on mating procedure:
- - Impregnation procedure: Cohoused
- If cohoused: Yes
- M/F ratio per cage: 1 male/5 females
- Length of cohabitation: Until confirmed pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.N/A
- Further matings after two unsuccessful attempts: N/A
- Verification of same strain and source of both sexes: [yes / no (explain)]
- Proof of pregnancy: Presence of sperm in the vaginal smear, being Day 0 of gestation.
- After successful mating each pregnant female was caged (how): Individually and was kept undisturbed except for specified injections.
- Any other deviations from standard protocol: N/A - Duration of treatment / exposure:
- Upto day 20 of gestation
- Frequency of treatment:
- On 5th, 10th, and 15th days of gestation
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 119.89, 359.67, 719.34 or 1198.805 mg/kg
Basis:
- No. of animals per sex per dose:
- Blunt needle (injection): 5 pregnant female rats
Distilled water: : 5 pregnant female rats
Normal saline: : 5 pregnant female rats
Cottonseed oil: : 5 pregnant female rats
Dipropyl adipate :
119. 89 mg/Kg: 5 pregnant female rats
359.67 mg/Kg: 5 pregnant female rats
719.34 mg/Kg: 5 pregnant female rats
1198.805 mg/Kg: 5 pregnant female rats - Control animals:
- other: Blunt end needle
- Details on study design:
- No Data Available
Examinations
- Maternal examinations:
- No Data Available
- Ovaries and uterine content:
- On the 20th day of gestation, 1 day prior to expected parturition, the rats were sacrificed by ether inhalation. The uterine horns and ovaries were surgically exposed to permit counting and recording of the numbers of corpora lutea, resorption sites, and viable and dead fetuses.
- Fetal examinations:
- Body weight : Mean fetal weights in the mid- and high-dose groups were significantly lower than in the control group.
Gross pathology: There was a significant increase of gross fetal abnormalities was noted in the mid and high dosed groups as compared to control.
Skeletal abnormalities: SSkeletal abnormalities occurred at only at higher dose i.e 5.3% .
Visceral abnormalities No changes were observed - Statistics:
- Acute LD50 values, 95% confidence limits, and slopes were calculated by Cornfield and Mantel’s modification of Karber’s method.
- Indices:
- No data available
- Historical control data:
- No data available
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only one resorption site was ohserved in the test chemical group. No other gross pathological effects were observed in the test chemical treated group.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Only one resorption site was ohserved in the test chemical group. No other gross pathological effects were observed in the test chemical treated group.
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only one resorption site was ohserved in the test chemical group. No other gross pathological effects were observed in the test chemical treated group.
- Early or late resorptions:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only one resorption site was ohserved in the test chemical group. No other gross pathological effects were observed in the test chemical treated group.
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- Only one resorption site was ohserved in the test chemical group. No other gross pathological effects were observed in the test chemical treated group.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 119.89 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- early or late resorptions
- gross pathology
- maternal abnormalities
- total litter losses by resorption
- Remarks on result:
- other: Not Specified
Maternal abnormalities
- Abnormalities:
- not specified
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- High cases of external malformations were observed at 719.34 or 1198.805 mg/kg.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- High cases of skeletal malformations were observed at 719.34 or 1198.805 mg/kg.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- High cases of Visceral malformations were observed at 719.34 or 1198.805 mg/kg.
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 119.89 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- LOAEL
- Effect level:
- 359.67 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) value of the test chemical was found to be 119.89 mg/kg bw/day.
- Executive summary:
A study was performed to evaluate and assess the effect of the test chemical on the maternal animals and on the fetus of the treated maternal animals. In this study, the test chemical was administered to the test animals via the intraperitoneal route at doses of 0, 119.89, 359.67, 719.34 or 1198.805 mg/kg/day on Day 5, 10 and 15 days of gestation with the test chemical. Female rats were selected for experimentation only after observation of at least two complete 4- or 5-day estrus cycles. Occurrence of estrus was determined by daily vaginal smears, obtained by introducing 0.2 ml. of fresh, clean tap water into the vagina with a smooth. clean. sterile medicine dropper, withdrawing a part of the liquid, and transferring it to a clean slide. The slide was examined microscopically while fresh, and the stage of estrus (proestrus, metstrus, or diestrus) was determined according to cell types found in the vaginal smear. Test animals were adult, virgin female, Sprague-Dawley rats, weighing 175-225 g. Adult, male rats of this strain were utilized as the “stud pool.” Five female rats were housed with one male in a large cage at room temperature (22-27“) with foods and fresh tap water provided ad libitum. The onset of gestation was established by the presence of sperm in the vaginal smear and was designated as Day 0. with the following day being Day 1 of the gestation period. At this time, the female rats were moved to individual cages, where they were kept undisturbed except for specified injections. There were 31 groups, each composed of five female rats. All treatments were administered by intraperitoneal injection on the 5th, 10th, and 15th days of gestation. On the 20th day of gestation, 1 day prior to expected parturition, the rats were sacrificed by ether inhalation. The uterine horns and ovaries were surgically exposed to permit counting and recording of the numbers of corpora lutea, resorption sites, and viable and dead fetuses.The parameters resorptions, number of corpora lutea, fetal survival, mean fetal weight and gross, skeletal and visceral abnormalities were analysed. No increased level of fetal deaths was noted and no effect of teratogenicity was observed. Slight increase in gross and skeletal abnormalities was observed at concentrations above 119.89 mg/kg/day of the test chemical. The no observed adverse effect level (NOAEL) value of diisopropyl adipate was found at dose level of 119.89 mg/kg/day since at this dose no effects were observed on rat fetuses.
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