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EC number: 233-054-0 | CAS number: 10026-04-7
- 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:
- weight of evidence
- Study period:
- No data
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 112926-00-8
- Test material form:
- solid: particulate/powder
- Remarks:
- powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Germany GmbH
- Age at study initiation: 12-15 weeks
- Weight at study initiation: 195.3- 271g
- Fasting period before study: Not relevant
- Housing: Individually in Macrolon type III cages, with a bedding of dust-free wood shavings and wooden gnawing blocks as environmental enrichment.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30-70%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: No data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: highly deionised water containing 10% foetal bovine serum
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Dosing formulations of synthetic amorphous silica were pre-pared with highly deionized water containing 10% foetal bovine serum in order to avoid agglomeration.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The formulations were analysed by scanning electron microscopy after shock freezing and in situ analytical ultracentrifugation.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1-2 untreated females with 1 untreated male
- Length of cohabitation: Not stated but mating occurred between 15:30 and 7.30 on the day after cohousing started.
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Gestation day 6-19
- Frequency of treatment:
- One dose per day
- Duration of test:
- Approximately 21 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- No. of animals per sex per dose:
- 25 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Highest dose was chosen as the limit dose according to the test guideline.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: described as 'regular'
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: described as 'regular'
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (described as 'regular')
WATER CONSUMPTION: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus and ovaries - Ovaries and uterine content:
- The ovaries and uterine content were 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, but no data on number examined - Statistics:
- The data for food consumption, maternal, litter weight and body weight change, carcass and gravid uterus weight, number of corpora lutea and implantations, number of resorptions, number of live foetuses, percent pre- and post- implantation loss, percent live foetuses per litter, number of pups per litter, post- implantation loss, and mean placental weights were analysed by the two-sided Dunnett’s test for the hypothesis of equal means. The female mortality, number of pregnant females, and number of litters with foetal proportions. Proportions of foetuses per litter with findings were analysed by pairwise comparison of each dose group with the control group by a one-sided Wilcoxon test for the hypothesis of equal medians.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related clinical signs occurred throughout the study.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- No treatment-related mortality occurred throughout the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No difference in the body weight or body weight gain occurred throughout the study.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No difference in the food consumption occurred throughout the study.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The average carcass weight was not affected by the treatment throughout the study.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related findings were observed at necropsy.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- A slightly higher pre-implantation loss occurred in the groups treated with SAS when compared to the control group. However, this was not considered as treatment-related as treatment started after implantation. No other differences occurred throughout the study.
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not examined
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Three rats of the control group, four rats of the low dose group and two animals of the high dose group were not pregnant. Since there was no dose-relationship occurring, the findings were not considered as treatment-related.
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The mean number of corpora lutea was not affected.
The blood coagulum around the placenta or fused placenta were observed for 1-2 littermates of the control, the mid and the high dose group. This was considered as spontaneous and therefore, not considered as treatment-related.
Some isolated cartilage findings without impact on the respective bony structures occurred in all groups including the controls. The observed cartilage findings were related to the skull and the sternum. Although, the incidence of notched manubrium was statistically significantly higher in the high-dose group which was within the historical control range. Therefore, these changes were not considered as treatment-related.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- Maternal
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: No adverse effects observed in maternal animals.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- The mean foetal weights did not show any biologically relevant differences between the test substance-treated groups and the control.
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- No differences in the sex distribution occurred throughout the study.
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One foetus in the low and one in the high dose group had multiple malformations. Mandibular micrognathia mirrored the severely malformed skull bones found during skeletal examination in one foetus. The changes were considered to be related to each other. The cleft palate observed in the other foetus is present in the historical control data at a comparable incidence. Both findings were considered to be spontaneous in nature and without a relation to dosing. The total incidence of external malformations in treated animals did not differ significantly from that of the control group.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Skeletal malformations were noted in single foetuses at dose levels of 0, 100 and 1000 mg/kg bw/day which affected individual foetuses. However, there were no statistically significant differences between the test groups and not a dose-response relationship. Additionally, the overall incidences of skeletal malformations were comparable to those found in the historical control data.
Skeletal variations of different bone structures were observed with or without effects on corresponding cartilage. The observed skeletal variations were related to several parts of foetal skeletons and appeared without a relation to dosing. The overall incidences of skeletal variations were comparable to the historic control data. There were no dosing-related statistical significance and the incidences were within historical control ranges and consequently, not considered as treatment-related. - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the control group, one soft tissue malformation, supernumerary unilateral liver lobes were observed in the control group. Three soft tissue variations i.e. short innominate, enlarged atrial chamber of the heart and uni- or bilateral dilation of renal pelvis were detected. However, no dose response occurred. The observable differences between the groups reflect the usual fluctuation for this parameter and were clearly withing the range of the historical control data.
- Other effects:
- no effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: There were no adverse effects on developmental parameters.
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1- Summary of reproductive and developmental results
Dose (mg/kg bw/d) | 0 (vehicle control) | 100 | 300 | 1000 | |
Females mated | N | 25 | 25 | 25 | 25 |
Pregnant | N | 22 | 21 | 25 | 23 |
Conception rate | % | 88 | 84 | 100 | 92 |
Aborted | N | 0 | 0 | 0 | 0 |
Premature births | N | 0 | 0 | 0 | 0 |
Dams with viable foetuses | N | 22 | 21 | 25 | 23 |
Dams with total litter loss | N | 0 | 0 | 0 | 0 |
Female mortality | N | 0 | 0 | 0 | 0 |
Pregnant at terminal sacrifice | N | 22 | 21 | 25 | 23 |
% | 88 | 84 | 100 | 92 | |
Corpora luteaD | mean ± SD | 14.2 ± 2.4 | 13.9 ± 2.08 | 14.0 ± 1.99 | 14.7 ± 2.03 |
Implantation sitesD | mean ± SD | 13.5 ± 2.56 | 12.5 ± 2.8 | 12.8 ± 1.62 | 13.4 ± 2.27 |
Pre-implantation loss (%)D | mean ± SD | 4.9 ± 7.31 | 9.4 ± 17.69 | 7.7 ± 11.81 | 8.4 ± 12.31 |
Post-implantation loss (%)D | mean ± SD | 8.3 ± 9.96 | 5.2 ± 5.22 | 9.9 ± 16.2 | 6.0 ± 3.56 |
Early resorptions (%)D | 7.6 ± 9.27 | 5.2 ± 5.22 | 9.9 ± 16.2 | 5.6 ± 3.75 | |
Late resorptions (%)D | 0.7 ± 2.26 | 0 | 0 | 0.3 ± 1.49 | |
Dead foetuses | 0 | 0 | 0 | 0 | |
Dams with viable foetuses | N | 22 | 21 | 25 | 23 |
Live foetusesD | mean ± SD | 12.4 ± 2.59 | 11.8 ± 2.71 | 11.5 ± 2.47 | 12.7 ± 2.23 |
Live foetuses (% implantation)D | mean ± SD | 91.7 ± 9.96 | 94.8 ± 5.22 | 90.1 ± 16.2 | 94.0 ± 3.56 |
MalesD | mean ± SD | 5.9 ± 1.7 | 5.5 ± 1.91 | 6.5 ± 1.85 | 5.7 ± 1.79 |
Males (%)D | mean ± SD | 43.7 ± 10.64 | 46.5 ± 18.79 | 50.9 ± 14.23 | 43.2 ± 13.09 |
FemalesD | mean ± SD | 6.5 ± 1.95 | 6.3 ± 2.76 | 5.0 ± 2.34 | 6.9 ± 2.21 |
Females (%)D | mean ± SD | 48.0 ± 11.17 | 48.3 ± 18.55 | 39.2 ± 15.98 | 50.9 ± 11.85 |
Sex ratio (% males) | 47.4 | 46.8 | 56.3 | 45.4 | |
Placental weightsD | mean ± SD | 0.47 ± 0.040 | 0.47 ± 0.042 | 0.46 ± 0.038 | 0.47 ± 0.038 |
N | 22 | 21 | 25 | 23 | |
Of male foetusesD | mean ± SD | 0.49 ± 0.038 | 0.48 ± 0.036 | 0.47 ± 0.043 | 0.48 ± 0.037 |
N | 22 | 21 | 25 | 23 | |
Of female foetusesD | mean ± SD | 0.46 ± 0.042 | 0.46 ± 0.052 | 0.46 ± 0.044 | 0.46 ± 0.041 |
N | 22 | 20 | 25 | 23 | |
Foetal weightsD | mean SD | 3.4 ± 0.26 | 3.4 ± 0.15 | 3.4 ± 0.24 | 3.4 ± 0.14 |
N | 22 | 21 | 25 | 23 | |
MalesD | mean SD | 3.5 ± 0.27 | 3.4 ± 0.18 | 3.5 ± 0.24 | 3.5 ± 0.14 |
N | 22 | 21 | 25 | 23 | |
FemalesD | mean SD | 3.3 ± 0.25 | 3.3 ± 0.17 | 3.4 ± 0.28 | 3.3 ± 0.15 |
N | 22 | 20 | 25 | 23 |
*p<0.05; **p<0.01 (D, two-sided Dunnett's test)
Table 2 - Summary of foetal malformations
Dose (mg/kg bw/d) | 0 (vehicle control) | 100 | 300 | 1000 | |
Litters evaluated | N | 22 | 21 | 25 | 23 |
Foetuses evaluated | N | 272 | 248 | 288 | 291 |
Total Malformations | |||||
Foetal incidence | N | 3 | 1 | 0 | 1 |
% | 1.1 | 0.4 | 0.0 | 0.3 | |
Litter incidenceF | N | 2 | 1 | 0 | 1 |
% | 9.1 | 4.8 | 0.0 | 4.3 | |
Affected foetuses per litterW | mean% ± SD | 1.3 ± 4.07 | 0.4 ± 1.98 | 0.0 ± 0.00 | 0.3 ± 1.60 |
*<0.05; **p<0.01 (F, one-sided Fisher's exact test; W, one-sided Wilcoxon)
Applicant's summary and conclusion
- Conclusions:
- In a developmental toxicity study, conducted according to OECD Test Guideline 414 and in compliance with GLP, the NOAEL for general systemic and developmental toxicity was concluded to be ≥1000 mg/kg bw/day based on no adverse effects observed.
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