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EC number: 701-133-3 | 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 23 Aug - 7 Sept 2000
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP-guideline study with acceptable restrictions. Dosing was performed on gestation day 6-17, 10 rats per dose group, no justification for the selected dose groups, analytical purity of the test substance was not specified.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- dosing performed on gestation day 6-17, 10 rats per dose group, no justification for the selected dose groups
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Details on test material:
- - Name of test material (as cited in study report): isononyl isononanoate
- Physical state: colourless liquid
- Analytical purity: no data
- Storage condition of test material: at room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley Crl CD(SD) IGS BR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River France, Saint Aubin-lès-Elbeuf, France
- Age at study initiation: approximately 11 weeks
- Weight at study initiation: 272 g (mean)
- Housing: the animals were housed individually in suspended wire-mesh cages (43.0 cm x 21.5 cm x 18.0 cm). A metal tray containing autoclaved sawdust (SICSA, Alfortville, France) was placed under each cage.
- Diet: A04 C pelleted diet, batch No. 90528 (U.A.R., Villemoisson-sur-Orge, France), ad libitum
- Water: tap water filtered using a 0.22 micron filter, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): approximately 12
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 17 Aug 2000 To: 7 Sept 2000
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: the solutions were prepared daily prior to dosing and homogenised using a magnetic stirrer. The solutions were stirred continously during the dosing procedure. The doses were adjusted according to the most recently recorded body weight.
VEHICLE
- Concentration in vehicle: 10, 33.33 and 100 mg/mL
- Amount of vehicle (if gavage): 3 mL/kg bw
- Lot/batch no. (if required): 107H1649 (Sigma, France) - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Day 6-17 of gestation
- Frequency of treatment:
- Daily, 7 days/week
- Duration of test:
- 12 days, Day 6-20 of gestation
- No. of animals per sex per dose:
- 10 P females
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily for mortality and signs of morbidity, at least once daily for clinical signs
- Cage side observations included: evidence of absorption/resorption, signs of toxicity
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 2 (prior to administration), 6, 9, 12, 15, 18 and 20 (prior to sacrifice). The net body weight change was calculated as (body weight on day 20 minus body weight on day 2)minus weight of gravid uterus.
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
WATER CONSUMPTION: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: ovaries, uterus, placenta, thoracic organs, abdominal organs - 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
- Other: number and distribution of dead and live foetuses - Fetal examinations:
- - External examinations: Yes: all per litter (sex, body weight, anomalities, malformations)
- Soft tissue examinations: Yes: half per litter (stored in Bouin's fluid)
- Skeletal examinations: Yes: half per litter (eviscerated, skeletons stained with alizarin red S)
- Head examinations: No - Statistics:
- Mean values were compared by one-way analysis of variance and Dunnett's test. Percentage values were compared by Fisher's exact probability test.
- Indices:
- Preimplantation loss:
((Number of corpora lutea - Number of implantation sites) / Number of corpora lutea) x 100
Post-implantation loss:
((Number of implantation sites - Number of live fetuses) / Number of implantation sites) x 100
Fetal findings:
(Number of fetuses with a particular finding/ total number of fetuses examined) x 100
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: 300 mg/kg bw/day: reduced body weight gain
Details on maternal toxic effects:
Systemic effects:
1/10 females in the control group died on gestation day 7. No clinical signs were observed prior to death, but during the histopathological examination the lungs were reddish and dilated. This may have been caused by mis-dosing, although the cause was not established. In 1/10 rats in the high-dose group, piloerection, abdominal breathing and chromorhinorrea were observed on gestation day 8 to 11, indicating a poor health condition. This animal also had a body weight loss of approximately 10% from gestation day 6 to 12. The body weight in females in the high-dose group was significantly reduced on day 15 and 18 (see Table 1). The body weight gain was significantly reduced over the periods gestation day 2-20, 6 to 18 and 6 to 12, indicating an effect during the entire dosing period (see Table 2). The food consumption was reduced in the high-dose group on gestation day 6-18, compared with the control group, although not statistically significant. The female exhibiting clinical signs had brownish content of the uterus and dilatation of the cervix. The effects may be toxicologically relevant. No other treatment-related effects were noted.
Fertility effects:
There was no effect on the fertility index, corpora lutea, resorptions, pre-implantation loss, post-implantation loss, fetal viability (in utero), gravid uterus weight and number of fetuses.
The slight, but not significant, increase in resorptions, pre-implantation loss and post-implantation loss observed in the high-dose group is attributable to a single female in poor health. The female in the high-dose group that exhibited clincial signs and body weight loss, and with histopatholocical findings, had several resorptions and dead fetuses. This is considered to be a consequence of the poor maternal health condition and is not a reproductive effect. All results were within the historical data range (see Table 6).
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
There were no statistically significant difference in embryo survival, sex ratio, body weight, malformations and abnormalities beween the control group and the treatment groups (see Table 4 and 5).
Effect levels (fetuses)
- Remarks on result:
- other: There were no statistically significant difference in embryo survival, sex ratio, body weight, malformations and abnormalities beween the control group and the treatment groups (see Table 4 and 5)
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1: Body weights, g (mean ± SD)
Dose group |
Control |
30 mg/kg bw/day |
100 mg/kg bw/day |
300 mg/kg bw/day |
Gestation day 2 |
250 ± 14 |
248 ± 13 |
248 ± 12 |
247 ± 15 |
Gestation day 6 |
272 ± 15 |
272 ± 13 |
272 ± 12 |
271 ± 14 |
Gestation day 9 |
287 ± 18 |
284 ± 17 |
280 ± 17 |
273 ± 26 |
Gestation day 12 |
311 ± 21 |
305 ± 16 |
295 ± 28 |
285 ± 31 |
Gestation day 15 |
330 ± 24 |
324 ± 19 |
315 ± 22 |
303 ± 19* |
Gestation day 18 |
370 ± 28 |
365 ± 22 |
348 ± 28 |
332 ± 25** |
Gestation day 20 |
400 ± 31 |
400 ± 26 |
385 ± 26 |
370 ± 25 |
*d-ANOVA + Dunnett-test, p < 0.05
**d-ANOVA + Dunnett-test, p < 0.01
Table 2: Body weight gain, g (mean % change)
Dose group |
Control |
30 mg/kg bw/day |
100 mg/kg bw/day |
300 mg/kg bw/day |
Day 2 to 6 |
9.1 |
9.6 |
9.8 |
9.9 |
Day 6 to 9 |
5.0 |
4.2 |
3.1 |
0.6 |
Day 9 to 12 |
8.3 |
7.5 |
5.3 |
4.7 |
Day 12 to 15 |
6.3 |
6.3 |
7.0 |
6.8 |
Day 15 to 18 |
12.0 |
12.5 |
10.5 |
9.6 |
Day 18 to 20 |
8.2 |
9.7 |
10.8 |
11.6 |
Day 2 to 20 |
60.2 |
61.0 |
55.7 |
50.2* |
Day 6 to 18 |
35.4 |
34.0 |
28.1 |
22.7** |
Day 6 to 12 |
13.7 |
12.0 |
8.6 |
5.2* |
*d-ANOVA + Dunnett-test, p < 0.05 (based on absolute mean body weight)
**d-ANOVA + Dunnett-test, p < 0.01 (based on absolute mean body weight)
Table 3: Reproduction parameters for dams with live foetuses
Dose group
|
Control |
30 mg/kg bw/day |
100 mg/kg bw/day |
300 mg/kg bw/day |
Number of dams at term |
9 |
10 |
10 |
10 |
Number of pregnant dams at term |
9 |
10 |
10 |
10 |
Corpora lutea (total) |
144 |
166 |
156 |
173 |
Corpora lutea per dam (mean ± SD)a |
16.0 ± 1.6 |
16.6 ± 3.0 |
15.6 ± 3.4 |
17.3 ± 2.5 |
Implantation sites (total) |
124 |
141 |
131 |
136 |
Implantation sitesa (mean ± SD) |
13.8 ± 1.6 |
14.1 ± 1.9 |
13.1 ± 2.8 |
13.6 ± 2.1 |
Pre-implantation loss (total)b |
20 |
25 |
25 |
37 |
Pre-Implantation loss (%) |
13.9 |
15.1 |
16.0 |
21.4 |
Resorptions + scars (total)b |
6 |
1 |
9 |
11 |
Resorptions + scars (% of implantation sites)b |
4.5 |
0.7 |
6.9 |
8.1 |
Resorptions + scars (mean ± SD)a |
0.7 ± 1.1 |
0.1 ± 0.3 |
0.9 ± 1.5 |
1.1 ± 2.1 |
Implant scars (total) |
0 |
0 |
0 |
0 |
Early resorptions (total)b |
3 |
1 |
8 |
11 |
Early resorptions as No. per dam (mean ± SD)a |
0.3 ± 0.7 |
0.1 ± 0.3 |
0.8 ± 1.5 |
1.1 ± 2.1 |
Late resorptions (total)b |
3 |
0 |
1 |
0 |
Late resorptions as No. per dam (mean ± SD)a |
0.3 ± 1.0 |
0.0 ± 0.0 |
0.1 ± 0.3 |
0.0 ± 0.0 |
Fetuses (total) |
118 |
140* |
122 |
125 |
Fetuses per dam (mean ± SD)a |
13.1 ± 2.3 |
14.0 ± 2.1 |
12.2 ± 4.2 |
12.5 ± 3.7 |
Live foetuses (%) |
98.3 |
100.0 |
100.0 |
99.2 |
Dead foetuses (%) |
1.7 |
0.0 |
0.0 |
0.8 |
Uterus weight(mean ± SD)a |
79.3 ± 11.2 |
84.1 ± 12.8 |
72.1 ± 23.8 |
69.7 ± 21.2 |
ad-ANOVA +Dunnett-test based on pooled variance
bFishers exact test
*p < 0.05
Table 4: Developmental parameters for offspring
Dose group
|
Control |
100 mg/kg bw/day |
300 mg/kg bw/day |
1000 mg/kg bw/day |
Number of live foetusesb(m/f) |
116 (62/56) |
140*(74/66) |
122 (58/64) |
124 (63/62) |
Sex ratio (m/f) |
0.53/0.47 |
0.53/0.47 |
0.47/0.53 |
0.50/0.50 |
Weights of live foetuses, g (mean ± SD)a |
3.79 ± 0.32 |
4.01 ± 0.24 |
3.91 ± 0.47 |
3.46 ± 0.54 |
ad-ANOVA +Dunnett-test based on pooled variance
bFishers exact test
*p < 0.05
Table 5: Results of skeletal examination of offspring
Dose group
|
Control |
100 mg/kg bw/day |
300 mg/kg bw/day |
1000 mg/kg bw/day |
External malformations, number (% of total)b |
1 (0.8%) |
0 (0%) |
0 (0%) |
0 (0%) |
External anomalies, number (% of total)b |
0 (0%) |
0 (0%) |
0 (0%) |
0 (0%) |
ad-ANOVA +Dunnett-test based on pooled variance
bFishers exact test
*p < 0.05
Table 6: Historical data
|
Mean value (range) |
Number of pregnant dams at term |
829 |
Corpora lutea per dam |
17.0 (14.6-21.5) |
Implantation sites |
14.0 (12.0-16.0) |
Pre-implantation loss as % of corpora lutea |
17.1 (5.0-30.0) |
Post-implantation loss as % of corpora lutea |
4.6 (0.0-16.6) |
Resorptions |
0.5 (0.0-2.3) |
Live foetuses, % of implantation sites |
95.4 (83.4-100) |
Applicant's summary and conclusion
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.
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