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EC number: - | 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
Endpoint summary
Administrative data
Description of key information
The key oral repeated dose toxicity study, conducted according to OECD Test Guideline 407 and in compliance with GLP, concludes a systemic NOAEL to be >=750 mg/kg bw/day in CD rats (Dow Corning Corporation, 1999).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 Days
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- No urinalysis was conducted
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CD (SD)IGS BR VAF/Plus
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Removed from study report
- Age at study initiation: 34-38 days
- Weight at study initiation: 122-152 g
- Fasting period before study: No
- Housing: Housed singly in stainless steel cages, with a mesh lid and floor. The cages were suspended above absorbent paper.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Eight days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22
- Humidity (%): 39-66
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Test substance was prepared for administration by adding the required amount of corn oil to a pre-weighed amount of test substance to give the required concentration for each group. The formulations were homogenised using a Silverson Laboratory Mixer.
VEHICLE
- Justification for use and choice of vehicle: Not stated
- Concentration in vehicle: Not stated
- Amount of vehicle: Total volume of the dosage was 5 ml/kg bw/day
- Lot/batch no.: Five batches were used: U8112, A8246, H8247, X8246 and A8153.
- Purity: Not stated - Analytical verification of doses or concentrations:
- yes
- Remarks:
- The homogeneity and concentration of the test substance in the vehicle was assessed using an atomic absorption spectrometry method.
- Details on analytical verification of doses or concentrations:
- The homogeneity of the test substance in the vehicle was previously assessed analytically in a trial preparation at concentrations of 20 and 200 mg/mL. Homogeneity was also assessed at the lowest concentration in this study (10 mg/mL) by analysing samples taken from the formulation prepared for administration on Day 1 of treatment. Samples were taken from the three positions in the mix initially and following restirring after 2 hours storage at 21°C. The concentrations of the test substance were also determined for formulations prepared for administration on Day 1 and 21 of treatment. The method of analysis was an adaption of an atomic absorption spectrophotometry method (no further details given).
The results of the analysis showed acceptable homogeneity of the formulation initially and after resuspension. The achieved concentrations on days 1 and 21 of treatment were satisfactory except for Group 2 on day 1, which was slightly low (88% of intended concentration). The Group 1 control for day 21 was found to contain a minor interference, however, as the method of analysis is not compound specific this could have come from any silicon containing substance. - Duration of treatment / exposure:
- 29 Days
- Frequency of treatment:
- Daily, seven days per week.
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 750 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Five
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on range-finding study.
- Rationale for animal assignment: Random
- Rationale for selecting satellite groups: No satellite groups
- Post-exposure recovery period in satellite groups: No post-exposure recovery group - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily during the first week of treatment and twice weekly during weeks 2 and 4.
- Cage side observations checked in table No.1 were included.
BODY WEIGHT: Yes
- Time schedule for examinations: Each animal was weighed on day 4 after arrival, on the day that treatment commenced, at weekly intervals throughout the treatment period and before necropsy.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION: Yes
- Time schedule for examinations: Daily visual inspection
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 30
- Anaesthetic used for blood collection: Yes (isoflurane/nitrous oxide)
- Animals fasted: Yes, overnight
- How many animals: All
- Parameters checked in table 2 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 30
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table 2 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Pretreatment, weeks 2 and 3, and during week 4 (over two days).
- Dose groups that were examined: All
- Battery of functions tested: In the hand observations (pretreatment and each week of treatment: exophthalmos, fur appearance, lacrimation, piloerection, reactivity to handling, removal from cage, salivation, vocalisation on handling, standard arena observations (pretreatment and each week of treatment: activity counts, arousal, convulsion, defaecation count, gait, grooming, palpebral closure, posture, rearing count, tremor, twitches, urination), manipulations (pretreatment and week 4: approach response, auditory startle reflex, body temperature, body weight, grip strength, landing footsplay, tail pinch response, pupil closure reflex, righting reflex, touch response), and motor activity (pretreatment and week 4). - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 3)
HISTOPATHOLOGY: Yes (see table 3) - Statistics:
- For numerical data recorded in the FOB, the following statistical analysis was performed: Where 75% of the data had the same value, a frequency analysis was performed based on the Mantel trend test. Where this test was considered unsuitable, Fisher's exact test of control group versus each treated group was performed. Where less than 75% of the data had the same value, Bartlett's test to evaluate homogeneity of variances was performed. If the result of this was not significant at the 1% level, a parametric analysis was performed, otherwise, unless a stabilising transformation (e.g. Log transformation) could be applied, a non-parametric analysis was performed. The parametric analysis consisted of a one-way analysis of variance (ANOVA). If significant, the ANOVA was followed by Williams' test for trend with increasing dose. Where Williams' test was considered unsuitable, multiple comparisons based on the t-test were performed. The non-parametric analysis performed was a Kruskal-Wallis one-way analysis of ranks. If significant, this was followed by Shirley's test for trend with increasing dose. Where Shirley's test was considered unsuitable, the treatment group mean ranks were compared against the control group, followed by a set of multiple comparisons. All of these comparisons were based on the Wilcoxon rank-sum test.
The significance of inter-group differences in haematology and blood chemistry was assessed by Student's t-test using a pooled error variance. For organ weights and body weight changes, homogeneity of variance was tested using Bartlett's test. Whenever this was found to be statistically significant a Brehrens-Fisher test was used to perform pairwise comparison, otherwise a Dunnett's test was used. Intergroup differences in macroscopic pathology and histopathology were assessed using Fisher's Exact test. - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Salivation was frequently observed shortly after dosing for the majority of the animals that received 250 or 750 mg/kg bw/day and on one occasion (day 20) for one female that received 50 mg/kg bw/day. Salivation had ceased by 1-2 hours after dosing. There were no other signs related to treatment.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no deaths.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Overall body weight gains for males that received the highest dose were slightly low when compared with those of the controls (91% of the control values). There was no similar effect for females at this dose. Overall body weight gains for females that received 50 or 250 mg/kg bw/day were low compared with the controls (76 and 87% of control values, respectively). However, in the absence of any dose relationship or effect at the highest dose, these differences were no considered to be related to treatment.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Food consumption for males that received the highest dose was marginally lower than that of the controls (95% of the control values). There was no similar effect for the females that received this dose. Food consumption for females that received 50 or 250 mg/kg bw/day was slightly lower than that of the controls (87 and 96% of the control values). However, in the absence of a dose-response or effect in the high dose group, the difference was not considered to be related to treatment.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- No difference between the treated or control groups.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Activated partial thromboplastin time was shorter for males that received 750 mg/kg bw/day. This single change was observed only in one sex and is not considered as treatment related. Other inter-group differences that attained statistical significance were minor and within normal background ranges at the laboratory and therefore, not considered to be related to treatment. The cellularity and composition of the bone marrow was not affected by treatment.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the hand observations: Compared with controls, males and females that received 750 mg/kg bw/day showed an increased incidence of piloerection during weeks 3 and 4 of treatment. Three females that received the highest dose showed coat staining during week 4 of treatment. However, this observation occurred in all treatment groups including the controls throughout the study and was considered to be of no toxicological significance.
Arena observations: A few treated animals showed a flattened gait during every week of treatment. This observation was also recorded in control females and in both sexes before treatment started, and therefore, was not considered to be related to treatment. Females that received the highest dose showed group mean arena activity and rearing scores slightly by consistently lower than those of the controls during all four weeks of treatment. These decreased mean scores were generally due to two or three individuals showing atypically low levels of activity, often preventing gait assessment due to insufficient locomotion, rather than a general decrease in activity.
There were no treatment-related effects on manipulation observations.
Animals of the high dose group showed lower forelimb grip strength values during week 4 of treatment compared with controls, although hind limb values were unaffected. However, the forelimb grip strength of these animals was also lower than controls before the start of treatment and all group means were within the background control range. Therefore, the difference was not attributed to treatment.
Motor activity scores within week 4 of treatment showed considerable intra- and inter- group variation, with high beam (rearing activity) scores for females in all treated groups tending to be lower than those of controls during the first half of the 60-minute recording period. However, no indication of a dose-related trend was observed. Additionally, low beam (general locomotor activity) scores were unaffected and high and low beam scores for males were similar in all groups. - Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- A thickened stomach wall was observed in one high dose female and one mid dose male. There was also a dark area in the glandular mucosa of the stomach in one high dose male, and a distended jejunum and abnormal contents in the gastrointestinal tract for one high dose male.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The only change considered to be related to treatment was acute inflammation in the glandular region of the stomach. This was observed in three males and two females that received the highest dose and in a single male that received 250 mg/kg bw/day. The change was considered likely to depend on a slight irritant effect of the test substance that resulted in the migration of acute inflammatory cells, predominantly neutrophils, to the affected area. No other inflammatory or degenerative changes or evidence of local cytotoxicity were observed.
There was a slight increase in the incidence of cortico-medullary mineralisation in the kidneys of females that received the highest dose, but this change is commonly observed in female rats and the difference was considered to be due to sampling variation. - Histopathological findings: neoplastic:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 50 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- gross pathology
- haematology
- histopathology: non-neoplastic
- other: Based on local effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 750 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Critical effects observed:
- no
- Conclusions:
- In a repeated 28-day oral toxicity study, conducted to a protocol similar to OECD Test Guideline 407 and in compliance with GLP, the systemic NOAEL for reaction mass of 3-(2,3-epoxypropoxy)propyltrimethoxysilane and triacetoxyvinylsilane was concluded to be ≥ 750 mg/kg bw/day in CD rats based on no adverse effects observed.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 750 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Klimish score of 2.
- System:
- gastrointestinal tract
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The key oral repeated dose toxicity study, conducted according to OECD
Test Guideline 407 and in compliance with GLP, concludes the systemic
NOEL to be 250 mg/kg bw/day (Dow Corning Corporation, 2000e). Oral
gavage administration of the test material at 50, 250 and 750 mg/kg
bw/day in corn oil to CD rats for four weeks was associated with signs
of low-level toxicity at 750 mg/kg bw/day and acute inflammation in the
glandular region of the stomach for animals given 750 mg/kg bw/day and a
single male given 250 mg/kg bw/day. Slightly low body weight gain and
food consumption observed for male animals that received the highest
dose, were considered to be non-specific indicators of toxicity.
Functional Observation Battery findings did not reveal any clear
evidence of neurotoxicity. Some animals that received the highest dose
showed signs of low-level toxicity including piloerection (males and
females) or reduced activity and rearing in the arena (females only).
Acute inflammation observed in the stomach and the salivation observed
for treated animals was considered to be the result of a slight local
irritant effect of the test substance, which is consistent with the
findings in skin and eye irritation studies. There were no other
inflammatory or degenerative changes, or any evidence of local
cytotoxicity. The toxicological significance of the shorter activated
partial thromboplastin time for males that received 750 mg/kg bw/day was
unclear. The systemic NOAEL is considered to be 750 mg/kg bw/day for
both sexes.
Justification for classification or non-classification
The overall LOAEL (based on local irritation of the stomach) is 250 mg/kg bw, indicating that classification with STOT RE 2, H373:May cause damage to organs (stomach) through prolonged or repeated exposure (oral route) is appropriate for the repeated dose toxicity endpoint in accordance with Regulation (EC) No. 1272/2008.
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