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EC number: 201-083-8 | CAS number: 78-10-4
- 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)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No data
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Reliability 1
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 112926-00-8
- Test material form:
- solid - liquid: suspension
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Orient Bio, Korea
- Age at study initiation: 6 weeks old at purchase
- Weight at study initiation: 187.9-205.3 grams for males and 143.3-167.1 grams for females
- Fasting period before study: No
- Housing: Two animals per cage were housed in stainless steel wire cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-23.3°C
- Humidity (%): 42.0-51.4 %
- Air changes (per hr): 10-15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
IN-LIFE DATES: No data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Distilled water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Colloidal silica NPs with 20 nm and 100 nm diameters were diluted in distilled water and each of the tested doses were formulated by dilution of the highest dose with distilled water. Working samples of each dose formulation were prepared daily during the study. The formulated test particles were homogenised by vortexing just prior to administration.
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Remarks:
- 20 nm synthetic amorphous silica particles
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- 20 nm synthetic amorphous silica particles
- Dose / conc.:
- 2 000 mg/kg bw/day (actual dose received)
- Remarks:
- 20 nm synthetic amorphous silica particles
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Remarks:
- 100 nm synthetic amorphous silica particles
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- 100 nm synthetic amorphous silica particles
- Dose / conc.:
- 2 000 mg/kg bw/day (actual dose received)
- Remarks:
- 100 nm synthetic amorphous silica particles
- No. of animals per sex per dose:
- Control and 2000 mg/kg bw/day: 15 (includes 5 animals for the recovery group);
500 and 1000 mg/kg bw/day: 10 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A 14-day dose range-finding study was conducted where 5 male and 5 female rats were randomly distributed to each dose groups so the final mean body weight was approximately equal. The highest dose was selected to 2000 mg/kg bw/day, middle dose to 1000 mg/kg bw/day and the low dose to 500 mg/kg bw/day. A negative control group was included where the animals received distilled water. Clinical signs and body weight were monitored throughout the study whereas gross pathology was examined on the scheduled necropsy day. No toxicity was observed at the highest dose tested, therefore, the main study used the same highest dose of 2000 mg/kg bw/day.
- Post-exposure recovery period in satellite groups: Control and highest dose group had 5 extra animals each, which were observed for a recovery period of two weeks following the 90-day treatment period.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed once daily after treatment for well-being, mortality and clinical signs of toxicity (no further detail).
DETAILED CLINICAL OBSERVATIONS: It is not clear how detailed the observations were as it was not described in the publication.
BODY WEIGHT: Yes
- Time schedule for examinations: Prior to the administration of the test substance and thereafter, once a week.
FOOD CONSUMPTION: Yes
g food per rat was calculated.
FOOD EFFICIENCY: No
WATER CONSUMPTION: Yes
- Time schedule for examinations: Daily, calculated by difference between supplied amounts and remaining amounts measured the next day.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Last week of 90-day treatment period
- Dose groups that were examined: Control and highest dose groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: The night before scheduled necropsy
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: The night before scheduled necropsy
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: For five animals per group of each sex during the last week of the 90-day treatment period. Total urine volume was calculated from the urine collected over a 24-h period.
- Metabolism cages used for collection of urine: Yes, for five animals from the control and highest dose group over a 3-h sampling period.
- Animals fasted: No data
- Parameters checked in Table 1 were examined.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see Table 2), on moribund or dead animals, and on all animals at the end of the 90-day exposure period.
HISTOPATHOLOGY: Yes (see Table 2), tissues from the control and highest dose group were examined histopathologically. - Statistics:
- Body weight values, feed and water consumption data, haematological data, blood biochemistry data, and organ weight values were analysed for homogeneity of variance using Levene’s test. One-way analysis of variance was performed to evaluate the significance of differences. If the variance was homogeneous and a significant difference was identified, Scheffe’s multiple comparison test was performed as a post hoc test. If the variance was not homogeneous, the data were analysed using Dunnett’s T3 test. Analysis of data from the recovery groups was performed using the Student’s t-test. All analyses were performed using Statistical Package for the Social Sciences version 19.0 software (SPSS Inc, Chicago, IL, USA).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Irrespective of particle size, no treatment-related clinical signs occurred during the experimental period for rats of either sex. A few occurrences of salivation, loss of fur and wound scratching were observed in the 2000 mg/kg bw/day group for 20 nm silica. However, due to the sporadic nature and no dose-dependency, the study authors concluded that these observations were not related to treatment.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred in any dose groups.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Regardless of SiO2 particle size, there were no statistically significant differences in body weight between treated rats and their respective control groups for either males or females.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were sporadic increases in food consumption for 20 nm silica and sporadic increases in food consumption for 100 nm silica. However, these differences were not considered as treatment-related.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were sporadic decreases in water consumption for 20 nm and 100 nm silica, however, these were not considered to be treatment-related.
- Ophthalmological findings:
- not specified
- Description (incidence and severity):
- The results were not reported although ophthalmoscopic examination was performed.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the high dose recovery group for 20 nm silica, a statistically significant increase in lymphocyte counts was observed compared to the control recovery group. There were no findings for the groups treated with 100 nm silica and therefore, the findings were not considered as treatment-related.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No differences between treated and control animals were observed for 20 nm silica. For females of the high dose recovery group treated with 100 nm silica, aspartate aminotransferase and creatine kinase concentrations were statistically significantly decreased compared with the controls.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences in urinalysis parameters in any treated group compared with the respective control groups for either 20 nm or 100 nm silica.
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Relative liver weight was statistically significantly decreased whereas the absolute and relative lung weights were statistically significantly increased in males of the 2000 mg/kg bw/day dose group exposed to 20 nm silica compared to the control group. A statistically significantly increase in absolute weights of kidney, lung and submandibular glands and a statistically significant increase in the relative weights of kidneys and lungs were observed in the male 2000 mg/kg bw/day recovery group exposed to 100 nm silica. Females in the high dose recovery group had statistically significantly decreased absolute and relative ovary weights. The study authors concluded that due to the sporadic nature of the organ weight findings, the observations were not treatment related. No further details are available.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pale yellowish discoloration on the posterior surface of the left lateral lobe of the liver was observed in one male animal from the 20 nm silica 500 mg/kg bw/day group. With regard to 100 nm silica, a small-sized right testis and epididymis were observed in one male from the 500 mg/kg group. A light yellow discoloration of the left lateral lobe of the liver (about 1 mm diameter), and a light yellow-coloured cyst with adjacent fat near the right kidney were also observed in another male in the 1000 mg/kg group. In addition, a small-sized left ovary was observed in one female from the 2000 mg/kg recovery group. However, no dose-dependency occurred and the effects were not considered to be related to treatment.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Granulomatous inflammation was observed in one male rat from the 1000 mg/kg bw/day group and two from the 2000 mg/kg bw/day group treated with 20 nm silica. Chronic bronchioalveolar inflammation was observed in one male rat from the 2000 mg/kg bw/day group treated with 20 nm silica. There were no adverse findings from the groups treated with 100nm silica. These lesions were observed in four cases in total and were minimal to mild in severity.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 2 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse observed effects were observed
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1 - Organ weights and organ weight to body weight ratios of male rats in the 90-day gavage study (main group) of 20 nm SiO2 nanoparticles*
0 (vehicle control) | 500 mg/kg bw/day | 1000 mg/kg bw/day | 2000 mg/kg bw/day | |
Number of animals | 10 | 10 | 10 | 10 |
Male | ||||
Necropsy body weight | 565.9±43.4 |
553.7±45.1 |
529.1±48.4 |
526.6±48.9 |
Liver | ||||
Absolute (g) | 14.70±1.90 |
13.65±1.26 |
13.11±1.94 |
12.59±1.71 |
Relative (%) | 2.59±0.18 |
2.47±0.14 |
2.47±0.16 |
2.38±0.11a |
*Organ (absolute) weights and body weights are given in grams: organ weight to body (relative) weights are given as mg organ weight/g body weight (mean ± standard deviation); aP<0.05 significantly different from control, by Scheffe’s test.
Table 2 - Organ weights and organ weight to body weight ratios for the recovery group in the 90-day gavage study of SiO2 nanoparticles*
0 (vehicle control) | 2000 mg/kg bw/day | |
Number of animals | 5 | 5 |
SiO2 (20 nm) | ||
Male | ||
Necropsy body weight | 569.8±38.4 |
545.9±35.0 |
Lung | ||
Absolute (g) | 1.61±0.07 |
1.81±0.12a |
Relative (%) | 0.28±0.02 |
0.33±0.02a |
SiO2 (100 nm) | ||
Male | ||
Necropsy body weight | 577.4±60.5 |
603.3±22.0 |
Kidney | ||
Absolute (g) | 3.27±0.21 |
3.69±0.21a |
Relative (%) | 0.57±0.03 |
0.61±0.02a |
Lung | ||
Absolute (g) | 1.62±0.09 |
1.93±0.08a |
Relative (%) | 0.28±0.02 |
0.32±0.02a |
Submaxillary gland | ||
Absolute (g) | 0.78±0.04 |
0.96±0.12a |
Relative (%) | 0.14±0.01 |
0.16±0.02 |
Female | ||
Necropsy body weight | 303.9±47.8 |
304.9±16.9 |
Ovary | ||
Absolute | 0.094±0.009 |
0.066±0.022a |
Relative | 0.0314±0.0040 |
0.0217±0.0069a |
*Organ (absolute) weights and body weights are given in grams: organ weight to body (relative) weights are given as mg organ weights/g body weight (mean ± standard deviation); aP<0.05, significantly different from control by Scheffe’s test.
Applicant's summary and conclusion
- Conclusions:
- In a 90-day oral repeated dose toxicity study, conducted according to OECD Test Guideline 408 and in compliance with GLP (reliability score 1), the NOAELs for 20 nm and 100 nm colloidal silica particles) were ≥2000 mg/kg bw/day in Sprague-Dawley rats based on the authors' conclusion of no adverse effects observed. Condensed polysilicic acid (equivalent to synthetic amorphous silica) is the primary hydrolysis product of tetraethyl orthosilicate.
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