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EC number: 203-419-9 | CAS number: 106-65-0
- 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:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 995
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Dibasic esters (DBE)
- IUPAC Name:
- Dibasic esters (DBE)
- Details on test material:
- - Name of test material: Dibasic esters
- Physical state: Liquid
- Analytical purity: >99.5%
- Composition of test material, percentage of components: Dimethyl glutarate - 65.12%; dimethyl succinate- 17.75%; dimethyl adipate - 16.83%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc, Kingston, NY, USA
- Age on arrival: 63 days
- Weight on arrival: 146-198 g
- Fasting period before study: None
- Housing: Individually housed in stainless steel wire mesh cages
- Diet (e.g. ad libitum): Ad libitum except during exposure
- Water (e.g. ad libitum): Ad libitum except during exposure
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25 deg C
- Humidity (%): 40 - 60%
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Mass median aerodynamic diameter (MMAD):
- >= 5.3 - <= 5.4 µm
- Remarks on MMAD:
- Particle size of 72 - 74% of generated aerosol < 10 micron
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: NYU style inhalation chamber
- Method of holding animals in test chamber: stainless steel "modules"
- Source and rate of air: Ambient air, rate not reported
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: nebuliser
- Temperature, humidity, pressure in air chamber: Measured but not reported
- Air flow rate: Not reported
- Air change rate: Not reported
- Method of particle size determination: Cascade impactor
- Treatment of exhaust air: Not reported
TEST ATMOSPHERE
- Brief description of analytical method used: Mass concentration determined gravimetrically following trapping on glass fibre filters. Identity by GC analysis of solvent traps collecting both aerosol and vapour
- Samples taken from breathing zone: yes
VEHICLE (if applicable)
- Justification for use and choice of vehicle: None used - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples were analysed by gas chromatography (GC/FID). Isothermal separation at 1500 deg C on glass column packed with 10% SP-1000 on Chromosorb W-AW 100/120 mesh. The GC response of the samples was compared with that obtained from standard samples prepared by quantitative dilution of DBE in acetone to determine chamber concentration. The method permitted separation / identification of the 3 components to determine changes in composition
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: Overnight
- Further matings after two unsuccessful attempts: Not reported
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy
- Any other deviations from standard protocol: No - Duration of treatment / exposure:
- Daily during gestation days 7 - 16, 6 hours / day
- Frequency of treatment:
- Daily during gestation days 7 - 16, 6 hours / day
- Duration of test:
- 21 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/L air
- Remarks:
- control
- Dose / conc.:
- 0.16 mg/L air
- Dose / conc.:
- 0.4 mg/L air
- Dose / conc.:
- 1 mg/L air
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Pilot study
- Rationale for animal assignment (if not random): Random following mating
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:Daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Gestation days 1, 7, 9, 11, 13, 15, 17 and 21
FOOD CONSUMPTION: Yes - Feed was weighed on Gestation Days 1, 3, 9, 11, 13, 15, 17, 19 and 21.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: Liver, ovaries (count of corpora lutea), uterus, pups - 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
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: half per litter - Statistics:
- Incidence of pregnancy, clinical observations, maternal mortality – Cochran-Armitage test for linear trend, Fisher’s exact test
Maternal weight, maternal weight change, food consumption – ANOVA, Dunnet’s test
Live fetuses, dead fetuses, resorptions, nidations, corpora lutea, foetal weight, incidence of foetal alterations - Jonckheere’s test, Mann-Whitney U test.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Perinasal staining and wet fur were seen in a number of animals of the 1.0 mg/L group (15 and 20 animals, respectively).
Perinasal staining was seen in 1 rat from the 0.16 mg/L group and in 4 rats from the 0.4 m/L group. Wet fur was seen in 1 rat from the 0.4 mg/L group.
Other observed clinical findings included alopecia, sores, periocular and facial staining, and swollen extremities. These were noted infrequently and with no suggestion of a dose-relationship. - Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes in body weight were reduced in rats exposed to either 0.4 or 1.0 m/L were reduced, This finding was not apparent in the mid-dose group (0.16 mg/L).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced in the 0.4 and 1.0 mg/L group rats during the first 6 days of exposures.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Reduced food consumption and reduced body weight gain noted in mid and high dose groups (treated at 0.4 and 1.0 mg/L) during exposure period.
Reduced liver weight noted in mid and high dose groups (treated at 0.4 and 1.0 mg/L) on termination
Effect levels (maternal animals)
- Dose descriptor:
- NOAEC
- Effect level:
- 1 mg/L air
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Reduction in number of live offspring:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects: no effects
Effect levels (fetuses)
- Dose descriptor:
- NOAEC
- Effect level:
- 1 mg/L air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: Lack of treatment-related effects in examined parameters
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Daily Dose (mg/L) |
0 |
0.16 |
0.4 |
1.0 |
Dams/Does: No. Pregnant No. Corpora Lutea/dam No. Implantations/dam |
24 17.8 14.7 |
21 17.2 13.8 |
20 18.1 14.3 |
24 17.7 13.7 |
Litters: No. Litters Evaluated No. Live Foetuses Mean Foetal Body Weight (g) Foetal malformations (% / litter): Gross External Visceral Anomalies Skeletal Anomalies Foetal variations (% / litter): Gross External Visceral Anomalies Skeletal Anomalies Foetal variations due to retarded development (% / litter): Gross External Visceral Anomalies Skeletal Anomalies |
24 326 3.36
0.0 1.1 0.6
7.4 4.5 15.9
0.0 0.0 30.5 |
21 265 3.55
0.3 3.1 1.7
4.3 1.3 8.0
0.0 0.0 27.7 |
20 263 3.32
0.0 0.7 0.4
14.9 2.0 19.0
0.0 0.0 25.2 |
24 300 3.35
0.3 5.1 3.4
11.7 4.2 21.4
0.0 0.0 31.7 |
Applicant's summary and conclusion
- Conclusions:
- The mixture, at the concentrations examined, does not cause developmental toxicity in the rat following inhalation exposure.
- Executive summary:
The potential developmental toxicity arising from inhalation exposure to bibasic esters, a mixture of dimethyl succinate, dimethyl glutarate and dimethyl adipate has been investigated. Groups of pregnant rats were exposed to concentrations of the mixture of 0.16, 0.4 or 1.0 mg/L by inhalation daily for 6 hours/day from Day 7 through to Day 16 of gestation (Day 1 was designated as the day in which evidence of mating was detected). A control group of pregnant rats was exposed to air only. All animals were killed on gestation Day 21 and the foetuses examined.
Both food consumption and the rate of body weight gain was slightly reduced in the 2 higher exposure groups (0.4and 1.0 mg/L) during the first week of exposure. Necropsy examination revealed a reduction in liver weight in the 2 higher exposure groups. None of the parameters examined as markers of reproductive toxicity were affected by treatment and no foetal effects were apparent.
The mixture is regarded as not causing developmental toxicity in the rat following inhalation exposures at concentrations as high as 1.0 mg/L during the period of organogenesis.
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