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EC number: 701-410-9 | 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
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- Nanomaterial specific surface area
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- 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)
Endpoint summary
Administrative data
Description of key information
There are no acute toxicity data for the registered substance, trimethoxy(methyl)silane and its reaction products with 3-aminopropyltriethoxysilane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (EC 701 -410 -9). Therefore, existing data for its constituents have been used for the assessment of acute oral, inhalation and dermal toxicity endpoints.
Block A
Trimethoxy(methyl)silane (CAS 1185-55-3)
In the acute oral toxicity study with trimethoxy(methyl)silane, conducted prior to OECD Test Guidelines and GLP, an LD50 value of 12.3 ml/kg (equivalent to 11685 mg/kg bw based on density of 0.95) was determined for male rats (Mellon Institute, 1963).
In the acute inhalation toxicity study with trimethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value was concluded to be >7605 ppm (equivalent to 42.1 mg/l) in rats (Dow Corning Corporation, 2006).
In the acute dermal toxicity study with trimethoxy(methyl)silane, conducted according to a protocol similar to OECD Test Guideline 402 but prior to GLP, the LD50 value was concluded to be >10 ml/kg (equivalent to 9500 mg/kg bw based on density of 0.95) in rabbits (Mellon Institute, 1963).
Triethoxy(methyl)silane (CAS 2031-67-6)
In the acute oral toxicity study with triethoxy(methyl)silane, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, there was no mortality or marked systemic effect in rats and the LD50 value was concluded to be >2007 mg/kg bw (Hazleton France, 1992a).
In the acute inhalation (aerosol) toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value was concluded to be >13.5 mg/l (Hoechst, AG., 1991).
In the acute dermal toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 402 and in compliance with GLP, the LD50 value was concluded to be >2007 mg/kg bw following 24-hour dermal exposure (Hazleton France, 1992b).
Block B
3-Aminopropyl(triethoxy)silane (CAS 919-30-2)
In the acute oral toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1175 (Acute Oral Toxicity) and in compliance with GLP, the LD50 values for female and male rats were 1.57 and 2.83 ml/kg bw, respectively (equivalent to 1492 and 2689 mg/kg bw based on density of 0.95) (Bushy Run Research Center, 1989).
In the acute inhalation toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, found no toxicity when male and female rats were exposed for 6 h to the substantially saturated vapour; the mean measured concentrations of the test material (after hydrolysis) were 5 and 16 ppm, for male and female rats, respectively. Therefore, the LC50 values were >5 and 16 ppm, for male and female rats, respectively (Bushy Run Research Center, 1982).
In the acute dermal toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1100 (Acute Dermal Toxicity) and in compliance with GLP, the LD50 value was 4.29 ml/kg bw in male and female rabbits (equivalent to 4076 mg/kg bw based on density of 0.95) (Bushy Run Research Center, 1989).
3-(Trimethoxysilyl)propylamine (CAS 13822-56-5)
In the acute oral toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 but pre-GLP compliance, the LD50 value was 2.97 ml/kg bw (equivalent to 3030 mg/kg bw based on density of 1.02) (Bushy Run Research Center, 1980).
In the acute dermal toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, the LD50 value was 11.3 ml/kg bw in male and female rabbits (equivalent to 11526 mg/kg bw based on density of 1.02) (Bushy Run Research Center, 1980).
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine (EC No. 701 -408 -8)
In the acute oral toxicity study with trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 value was concluded to be >2000 mg/kg bw (Dow Corning Corporation, 1990a).
In the acute dermal toxicity study with trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine conducted according to OECD Test Guideline 402 and in compliance with GLP, the LD50 was concluded to be > 2000 mg/kg bw (Dow Corning Corporation, 1990b).
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1963
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Method: 6 male rats were dosed at 6 and 18 ml/kg by peroral intubation of the undiluted test substance. The observation period was 14 days.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Carworth Farms-Eliss
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: The rats were reared at the Mellon Institute
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 90-120g
- Fasting period before study: no
- Diet: Rockland complete rat diet - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 1.9ml
- Doses:
- 16 and 8 ml/kg
- No. of animals per sex per dose:
- 5M
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes - Statistics:
- The method of moving average was used for calculating the median effective dose (LD50)
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 12.3 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 9.98 - < 15.3
- Remarks on result:
- other: equivalent to 11685 mg/kg bw based on density of 0.95
- Mortality:
- Most deaths occurred within the first several hours after dosing.
- Clinical signs:
- other: The animals were sluggish and unsteady in gait soon after dosing.
- Gross pathology:
- At autopsy, gross examination revealed congested lungs, mottled livers with prominent acini and some haemorrhage and congestion of the gastrointestinal tract.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute oral toxicity study with trimethoxy(methyl)silane, conducted prior to OECD Test Guidelines and GLP, an LD50 value of 12.3 ml/kg ( equivalent to 11685 mg/kg bw based on density of 0.95) was determined for male rats.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 16.09.1991 to 13.03.1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Iffa-Crédo, FRANCE
- Age at study initiation: 5-7 wk
- Weight at study initiation: 136-228 g
- Fasting period before study: 17-18 hr
- Housing: 5/cage (separate sexes), polycarbonate cages
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12 h/12 h
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- VEHICLE
none
MAXIMUM DOSE VOLUME APPLIED: 2.23 ml/kg bw - Doses:
- main study: 2007 mg/kg bw
preliminary study: 504, 1008, 2007 mg/kg bw - No. of animals per sex per dose:
- main study: 5
preliminary study: 2 - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days (changes to skin and fur, eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.)
- Frequency of observations and weighing: deaths and abnormal clinical signs were noted 15 minutes after administration, then 1, 2 and 4 h then daily for 14 days; weighed on day before treatment (day -1), immediately prior to administration of the test substance (day 1), and on Days 8 and 15.
- Necropsy of survivors performed: yes, after the 14 day observation period (Day 15), with particular attention paid to the following organs: liver, heart, kidneys and lungs. - Statistics:
- The body weights of the animals were evaluated for each sex. The mean, standard deviation and coefficient of variation were calculated. There were no deaths so an LD50 could not be calculated.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 007 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: No deaths at any dose.
- Sex:
- male/female
- Dose descriptor:
- LD0
- Effect level:
- > 2 007 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths throughout the study.
- Clinical signs:
- other: Main study (2007 mg/kg bw) Subdued behaviour in all treated animals at 1, 2 and 4 h, no overt clinical effects at Day 2.
- Gross pathology:
- No remarkable macroscopic findings.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute oral toxicity study with triethoxy(methyl)silane, conducted in according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, there was no mortality or marked systemic effect in rats and the LD50 value was concluded to be 2007 mg/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- No follow up study in females; limited detals of clinical examinations and pathology,
- GLP compliance:
- no
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no details
- Age at study initiation: 3-4 wk
- Weight at study initiation: 90-120 g
- Fasting period before study: no details
- Housing: no details
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details
ENVIRONMENTAL CONDITIONS
no details
IN-LIFE DATES: no details - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
-
MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw (neat test substance) - Doses:
- 1.25, 2.5, 5.0 ml/kg bw
- No. of animals per sex per dose:
- 5 males/dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighed at days 0 and 14; no details on frequency of observations
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Statistics:
- Moving average method.
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2.97 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1.67 - < 5.28
- Remarks on result:
- other: equivalent to 3030 mg/kg bw based on density of 1.02
- Mortality:
- See table 1.
- Clinical signs:
- other: See table 1.
- Gross pathology:
- Among the survivors at 2.5 ml/kg bw, the rat with weight loss (see table 1) had pus in the lungs. No other remarkable findings in survivors. Those that died had purple colouration in the glandular stomach.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute oral toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 but pre-GLP compliance, the concluded LD50 value was 2.97 ml/kg bw (equivalent to 3030 mg/kg bw based on density of 1.02).
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- This relatively comprehensive report does not provide all the information that would be required by current guidelines; information on the duration of acclimatization and housing conditions would also be required.
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.1175 (Acute Oral Toxicity)
- Version / remarks:
- (as stated in SIAR, 2003, not evident from study report seen by this reviewer)
- GLP compliance:
- not specified
- Remarks:
- SIAR (2003) notes that this laboratory was certified at the date of this study
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no details given
- Age at study initiation: no details given
- Weight at study initiation: 200-300 g
- Fasting period before study: overnight
- Housing: no details given
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details given
ENVIRONMENTAL CONDITIONS
no details given
IN-LIFE DATES: no details given - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- VEHICLE
n/a
MAXIMUM DOSE VOLUME APPLIED: 4 ml/kg bw - Doses:
- 4, 2, and 1 ml/kg bw in males; 2, 1.41 and 1 ml/kg bw in females
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily, weighing weekly
- Necropsy of survivors performed: yes; No microscopic exam was conducted on animals dosed at 1 ml/kg. Kidneys and urinary bladders from 5 animals (3 females, 2 males) dosed at 2 ml/kg bw, and 2 males dosed at 4 ml/kg bw were examined histologically.
- Other examinations performed: clinical signs, body weight, histopathology (kidney and urinary bladder of: 2 males at 4 ml/kg bw; 2 males and 3 females at 2 ml/kg bw. - Statistics:
- Moving Average Method (Thompson, 1974; Weil, 1983)
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2.83 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1.61 - < 4.98
- Remarks on result:
- other: equivalent to 2689 mg/kg bw based on density of 0.95
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1.57 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1.34 - < 1.85
- Remarks on result:
- other: equivalent to 1492 mg/kg bw based on density of 0.95
- Mortality:
- Deaths at 1.41 and 2 ml/kg bw in females and at 4 and 2 ml/kg bw in males. No deaths in either sex at 1 ml/kg bw. See table 1.
- Clinical signs:
- other: See table 1
- Gross pathology:
- See table 2
- Other findings:
- - Histopathology: examination of the kidneys and urinary bladders of a selected group revealed tubular necrosis in those that died and some evidence of lesser kidney damage in those that survived (see table 2).
- Potential target organs: kidney - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- In the acute oral toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1175 (Acute Oral Toxicity) and in compliance with GLP, the concluded LD50 values for female and male rats were 1.57 and 2.83 ml/kg bw, respectively.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 02 August 1990 to 22 October 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- 1987
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: The test substance was administered undiluted.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not specified
- Preliminary purification step (if any): not specified
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Michigan
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: young adults
- Weight at study initiation: 205-267 g
- Fasting period before study: 16 hours
- Housing: Housed individually in conventional design stainless steel, wire mesh bottom cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: not specified
DOSAGE PREPARATION: undiluted
CLASS METHOD
- Rationale for the selection of the starting dose: standard method used - Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed frequently on the day of dosing and twice a day thereafter. Animals were weighed prior to dosing, then at 24 hours after dosing and on days 7 and 14 thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- One female died spontaneously. No other deaths were recorded.
- Clinical signs:
- other: No clinical signs of systemic toxicity were noted in any of the animals.
- Gross pathology:
- The female that died spontaneously showed gross tissue changes consistent with acute gastritis with regurgitation and inspiration of test material. No such lesions were reported in the rest of the animals. Therefore, this change was considered to be due to gavage treatment. No gross macroscopic changes were noted in the rest of the animals.
- Other findings:
- - Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute oral toxicity study, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, an LD50 value of >2000 mg/kg bw was concluded.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: RCC Ltd., Switzerland
- Age at study initiation: males, 8 weeks, females 10 weeks
- Fasting period before study: 16-20 hours
- Housing: Groups of 3/sex, in Makrolon type-4 cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 'Under laboratory conditions, after health examination. Only animals without any visible signs were used for thhhe study.'
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 /- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 2 ml/kg bw
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 3 males, 3 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and viability were observed once daily during acclimatization period and 1, 2, 3 and 5 hours after test item administration on test day 1 and twice daily during days 2-15. Each animal was examined for changes in appearance and behaviour once daily during the acclimatization phase. 1, 2, 3 and 5 hours after test item administration on test day 1, and once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes - Statistics:
- No statistical analysis was used.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No death occurred during the study.
- Clinical signs:
- other: In one female, ruffled fur and hunched posture were noted on test day 1. No clinical signs were evident from test day 2 until the end of the observation period.
- Gross pathology:
- No macroscopic findings were observed at necropsy.
- Other findings:
- None reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral toxicity study with N-ethyl-3-trimethoxysilyl-2-methyl-propanamine, conducted according to OECD Test Guideline 423 and in compliance with GLP, the LD50 value was concluded to be >2000 mg/kg bw.
Referenceopen allclose all
Table 1: Number of animals dead and time range within which mortality occurred
Dose |
Mortality (# dead/total) |
Time range of deaths (days) |
||
Male |
Female |
Combined |
||
16.0 |
4/5 |
- |
4/5 |
0,1 |
8.0 |
0/5 |
- |
0/5 |
- |
Table 1: Number of animals dead
Dose |
Mortality (dead/total) |
||
Male |
Female |
Combined |
|
504a |
0/2 |
0/2 |
0/4 |
1008a |
0/2 |
0/2 |
0/4 |
2007a |
0/2 |
0/2 |
0/4 |
2007b |
0/5 |
0/5 |
0/10 |
a. preliminary study
b. main study
Table 1: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]
Dose |
Mortality (dead/total) |
Time range of deaths (days) |
Overt toxicity |
Weight change (g) |
Male |
||||
1.25 |
0/5 |
- |
- |
75 to 107 (mean 95) |
2.5 |
2/5 |
0,5 |
Sluggish @ 10 mins; one death @ 15 mins. |
-31 to 108 (mean 61) |
5.0 |
4/5 |
0,0,0,5 |
Sluggish and unsteady gait @ 2 mins; salivation @ 10 mins; death of 3 @ 6 min-2.5 h. |
125 |
Table 1: Number of animals that died, time range for mortality, body weight change and overt toxicity
Dose |
Mortality (dead/total) |
Time range of deaths (days) |
Mean body weights (days 0/7/14) (g) |
Overt toxicity |
||||
Male |
Female |
Combined |
Male |
Female |
Male |
Female |
||
1.00 |
0/5 |
0/5 |
0/10 |
- |
238/278/304 |
211/231/241 |
None. |
Sluggishness, recovery at 2 days. |
1.41 |
- |
1/5 |
- |
1 |
- |
212/227/234 |
- |
Sluggishness, periurogenital staining (positive for blood), red encrusted fur around nose; survivors recovered at 2 days. |
2.00 |
1/5 |
5/5 |
6/10 |
2-4 |
234/251/302 |
223/-/- |
Sluggishness, unkempt appearance, periurogenital brown staining, red encrusted fur around nose and eyes, closed eyelids, emaciation and diarrhoea. Survivors recovered at 5 to 9 days. |
Sluggishness, lacrimation, unkempt appearance, red encrusted fur around nose and eyes and diarrhoea. |
4.00 |
4/5 |
- |
- |
1-2 |
244/254/283 |
- |
Sluggishness, lacrimation, kyphosis (curvature of the thoracic spine), piloerection and red encrusted fur around nose. Survivor recovered at 3 days. |
- |
Table 2: Gross and microscopic examinations
Dose |
Gross examination |
Microscopic examination of kidneys and urinary bladder |
||
Male |
Female |
Male |
Female |
|
1.00 |
Nothing remarkable. |
Nothing remarkable. |
- |
- |
1.41 |
- |
Victim: lungs dark red; stomach (glandular) white to dark red; intestine filled with yellow liquid. Survivors: nothing remarkable. |
- |
- |
2.00 |
Victim: bright red lungs; dark red (glandular) stomachs filled with light brown liquid. Survivors: nothing remarkable. |
Victims: lungs bright pink; stomachs (glandular) dark red or mottled; stomachs and intestines filled with light brown liquid; intestines of one yellow; kidneys dark red. |
Examined 2 survivors: moderate renal tubular hyperplasia (indicative of prior necrosis) and mild tubular mineralization in 1; no urinary bladder lesions |
Examined 3 victims: moderate tubular necrosis; mild to moderate tubular mineralization; moderate kidney congestion; no urinary bladder lesions |
4.00 |
Victims: dark red, mottled lungs; dark red (glandular) stomachs; stomachs and intestines filled with yellow liquid; spleen mottled, dark red. Survivor: nothing remarkable. |
- |
Examined 2 victims: moderate tubular necrosis; marked kidney congestion; epithelial necrosis in the urinary bladder (only 1 rat examined). |
- |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, 401 S. New Hope rd., Raleigh, NC 27610
- Age at study initiation: ca. 9 weeks
- Weight at study initiation: Females: 218.2-226.2 g, Males: 311.9-351.7 g
- Housing: Individually housed in suspended wire-mesh cages during quarantine/acclimation period and during the in-life portion of the study.
- Diet: Certified Rodent Chow #5002, ad libitum, except during exposure
- Water: Municipal water, further purified by reverse osmosis, ad libitum, except during exposure
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: not applicable
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A Rochester - type, stainless steel and glass, whole body chamber.
- Exposure chamber volume: 450 litres
- Method of holding animals in test chamber: The animals were positioned in stainless steel exposure caging (two levels of 10 wire mesh cages).
- Source and rate of air: The source of air was a Nash Air Compressor (Model/size AL-574) The test article was metered from a reservoir under nitrogen head space, into the J tube using a Fluid Metering Incorporated pump. Compressed air flowed through the J-tube at a controlled rate of ca 30L/min. The carrier/vapour mixture passed from the J-tube to the inlet port at the top of the exposure chamber. Just prior to entering the exposure chamber, the carrier/vapour mixture combined with chamber supply air (dilution air) and was diluted to the target chamber concentration as it enters the exposure chamber.
- Method of conditioning air: The compressed air which acted as a carrier, was passed through a series of filters to remove contaminants prior to use in test atmosphere generation. Conditioned building air was passed through HEPA and activated charcoal filetrs before delivery to the chamber. Moisture was added as necessary to maintain relative humidity within the required range.
- System of generating particulates/aerosols: Generation of test article vapour concentration was performed using a heated stainless steel J-tube containing a column of stainless steel beads.
- Temperature, humidity, pressure in air chamber: The exposure chamber was operated under dynamic conditions with regard to airflow, temperature, relative humidity and pressure. Chamber temperature was maintained within the range of 21.9-26.4°C, humidity within 37.5-60%. Each exposure chamber contained a temperature/humidity sensor, which was monitored.
TEST ATMOSPHERE
- Brief description of analytical method used: The test article reservoir weight was determined pre- and post-exposure. These data, along with the chamber airflow rate and the vapour generation time, were used to calculate a nominal chamber concentration of test article. In the presence of moisture, methyltrimethoxysilane has the potential to hydrolyze, leading to the formation of methyl alcohol. Therefore, actual chamber concentrations of both test article and methyl alcohol were analyzed using a Varian 3400 gas chromatograph equipped with a flame ionization detector. The concentration of test article and methyl alcohol in the chamber atmosphere during the exposure period was evaluated approximately once every 30 minutes.
- Samples taken from breathing zone: yes
CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The limit test concentration was selected based on the lower explosive level of the material. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 6 h
- Concentrations:
- 8000 ppm (nominal), 7605 ppm (analytical)
- No. of animals per sex per dose:
- 5M/ 5F
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were carried out daily and body weights were recorded just prior to exposure on day 1, again on day 8 and prior to terminal sacrifice on day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Signs of toxicity including, but not limited to, changes in the skin and fur, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, motor activity and behaviour pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All animals were euthanized on day 15 and subjected to a complete gross pathology examination (no tissues were saved). - Statistics:
- The mean chamber concentration of the test substance was calculated along with the standard deviation. Additionally, chamber environmental conditions, including temperature, humidity and airflow were monitored continuously and recorded ca. every 30 min. Mean and standard deviation were calculated for each of these parameters.
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 7 605 ppm
- Based on:
- test mat.
- Exp. duration:
- 6 h
- Remarks on result:
- other: equivalent to 42.1 mg/L
- Mortality:
- No mortalities reported.
- Clinical signs:
- other: Urine staining, discoloured urine, fecal staining, head and muzzle soiling, with all females returning to normal by post exposure day 4. Four of the 5 males were reported normal by post exposure day 5, and all males were normal by post exposure day 10.
- Body weight:
- Body weights and body weight gains were within normal limits over the duration of the study for all females. Two of the five males demonstrated weight loss during the first week post-exposure, with a return to normal weight gain during the second week.
- Gross pathology:
- Necropsy findings included urinary bladder calculi and kidney foci in both sexes, an enlarged kidney in one male, and abcessed prostrate glands in two males. Urinary tract and prostate disease was attributed to urolithiasis of uncertain primary aetiology; a direct role for the test article in the formation of urinary calculi could neither be confirmed nor denied as a result of this study.
- Other findings:
- No other effects reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute inhalation toxicity study with trimethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the concluded LC50 value was >7605 ppm (equivalent to 42.1 mg/L) in rats.
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- from 3 Sept to 17 Sept 1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hoechst AG, SPF-Zucht, GERMANY
- Age at study initiation: 8-10 wk
- Weight at study initiation: males 188 (184-191) g; females 190 (185-200) g
- Housing: 1/plastic cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12h/ 12 h
IN-LIFE DATES: From: 1991-09-03 To: 1991-09-17 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
[from report in German]
- Exposure apparatus: cylindrical plastic cages housed in stainless steel inhalation chamber
- Exposure chamber volume: total volume 60 L
- Method of holding animals in test chamber: rats were fitted into test tubes with a coned end reaching into the test chamber
- Source and rate of air: 800 L/h
- Method of conditioning air: air was led at a constant pressure of 4 bar into a nozzle and through separators and filters
- System of generating particulates/aerosols: test substance was injected contineously into the air flow in the nozzle, primary aerosol built in a four-necked round-bottom flask, through a riser-pipe secondary arosol (smaller particle size) reached the test chamber
- Method of particle size determination: determination not possible
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography with FID detector
- Samples taken from breathing zone: yes
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not given
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not given
- Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 13.5 mg/L
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 2/day; weights on Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: no other examinations - Statistics:
- Single exposure concentration - no statistics presented.
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 13 500 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- 1/5 males; 0/5 females
- Clinical signs:
- other: Ataxia, irregular respiration, stupor, altered gait, prostration, tonic convulsions, trembling and reduced spontaneous activity were seen in both sexes during the 14-day observation period.
- Body weight:
- No treatment-related effect identified.
- Gross pathology:
- 1/5 males had dark red, patchy lungs. [The extent of examination is unclear.]
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute inhalation (aerosol) toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the concluded LC50 value was 13.5 mg/L.
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- [as stated in SIAR, 2003, not evident from the study report seen by this reviewer
- GLP compliance:
- not specified
- Remarks:
- SIAR (2003) notes that this laboratroy was GLP certified at the date of this study
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: "Hilltop Wistar" - no further details given
- Age at study initiation: not stated
- Weight at study initiation: 200-300 g
- Fasting period before study: no details
- Housing: no details
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details
ENVIRONMENTAL CONDITIONS
- Temperature (°C): mean chamber concentration 25
- Humidity (%): no details
- Air changes (per hr): no details
- Photoperiod (hrs dark / hrs light): no details
IN-LIFE DATES: no details - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic
- Exposure chamber volume: 9 l
- Method of holding animals in test chamber: not stated
- Source and rate of air: 2.5 l air/min passed through neat sample at 19 deg C then through test chamber
- Method of conditioning air: air passed through neat sample of test material at 19 deg C
- Temperature, humidity, pressure in air chamber: test chamber 25 deg C, no further details
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes, taken from exposure chambers
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: -
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): - - Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- gas chromatography
- Duration of exposure:
- 6 h
- Remarks on duration:
- OECD 403 recommends exposure for 4 h
- Concentrations:
- "Substantially saturated vapour", measured concentration 5 (+/-2) ppm (males) and 16 (+/-5.8) ppm (females) test material in the test chambers.
The test material concentration in vapour passing to the female test chamber was 90 ppm. Reaction with moisture in the test chambers (from exhaled air and urine) resulted in extensive hydrolysis to ethanol and unspecified other products. Ethanol concentrations of 380 and 490 ppm were reported for test chambers containing the males and females, respectively. [16 ppm would be equivalent to around 145 mg/m3.] - No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, body weights on days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Statistics:
- None
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- > 5 ppm
- Exp. duration:
- 6 h
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- > 16 ppm
- Exp. duration:
- 6 h
- Mortality:
- None (see table 1).
- Clinical signs:
- other: None (see table 1). Full data are not presented.
- Body weight:
- See table 1
- Gross pathology:
- None (see table 1). Full data are not presented.
- Other findings:
- None
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute inhalation toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, found no toxicity when male and female rats were exposed for 6 h to the substantially saturated vapour; the mean measured concentrations of the test material (after hydrolysis) were 5 and 16 ppm, for male and female rats, respectively. Therefore, the concluded LC50 values were >5 and 16 ppm, for male and female rats, respectively.
Referenceopen allclose all
.
Table 1: Concentration and mortality per animals treated
Analytical Conc. (mg/L) |
Mortality (dead/total) |
||
Males |
Females |
Combined |
|
13.5 |
1/5 |
0/5 |
1/10 |
Table 1: Concentrations, mortality or evident toxicity
Sex |
Analytical Conc. (ppm) |
Mortality (No./total) |
Mean body weight change (g) 0-7 days |
Mean body weight change (g) 0-14 days |
Number with overt toxicity |
Number with remarkable gross pathology |
males |
5 (+/- 2) |
0/5 |
51 (36-61) |
71 (62-79) |
0/5 |
0/5 |
females |
16 (+/- 5.8) |
0/5 |
10 (5-14) |
18 (9-27) |
0/5 |
0/5 |
LT50
(median lethal time)
Males: > 6.0 h
Females: > 6.0 h
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1963
- 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 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- occlusive dressings used
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: 'produced locally'
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 2.5kg
- Diet: Rockland rabbit ration - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Type of wrap if used: vinylite or polyethylene sheeting - Duration of exposure:
- 24 hours
- Doses:
- 10 ml/kg
- No. of animals per sex per dose:
- 4
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Statistics:
- None
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- > 10 mL/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: equivalent to 9500 mg/kg bw based on density of 0.95.
- Mortality:
- No animals died (0/4).
- Clinical signs:
- other: Little skin irritation was observed but some desquamation was found after 14 days.
- Gross pathology:
- None reported.
- Other findings:
- None reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 but prior to GLP, the concluded LD50 value was >10 ml/kg (equivalent to 9500 mg/kg bw based on density of 0.95) in rabbits.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 16.09.1991 to 10.03.1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Iffa-Crédo, FRANCE
- Age at study initiation: 6-8 wk
- Weight at study initiation: 212-259 g (variability within sex <20%)
- Fasting period before study: none specified
- Housing: 1/F1 polycarbonate cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1991-11-18 To: 1991-12-03 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: back and flanks
- % coverage: approx 10%
- Type of wrap if used: semi-occlusive (perforated adhesive band/elastic crepe bandage)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with Codex absorbant gauze
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2007 mg/kg bw (2.23 mL/kg bw)
- Concentration (if solution): neat liquid - Duration of exposure:
- 24 h
- Doses:
- 2007 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 0 and 15 mins, 1, 2 and 4 h, then daily until study completion at 15 days; weighting on Days 0, 8 and 15. The daily observations performed, amongst others, included changes in the fur, in the treated skin, the eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarhoea, lethargy, sleeping and coma were noted with particular attention.
- Necropsy of survivors performed: yes, on Day 15 all rats were killed and necropsied. Particular attention was paid to liver, heart, kidneys, lungs and skin of application site.
- Other: Cutaneous lesions were evaluated daily for each rat from Days 2 to 15, according to a scale equivalent to that of Draize. - Statistics:
- The body weights of the animals were evaluated for each sex, calculating the mean of the values obtained, the standard deviation, the coefficient of variation which indicates the homogeneity of the data.
As no deaths were observed an LD50 could not be calculated. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 007 mg/kg bw
- Based on:
- test mat.
- Mortality:
- 0/10
- Clinical signs:
- other: No effects reported.
- Gross pathology:
- No abnormal observations.
- Other findings:
- No local effects (erythema or oedema).
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 402 and in compliance with GLP, the concluded LD50 value was >2007 mg/kg bw following 24-hour dermal exposure.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- Ony 4 males tested at each dose; no follow-up assessment in females. Occlusive covering. Limited detail of clinical examinations and pathology.
- GLP compliance:
- no
- Test type:
- standard acute method
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no details
- Age at study initiation: 3-5 months
- Weight at study initiation: no details
- Fasting period before study: no details
- Housing: no details
- Diet (e.g. ad libitum): no details
- Water (e.g. ad libitum): no details
- Acclimation period: no details
ENVIRONMENTAL CONDITIONS
no details
IN-LIFE DATES: no details - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: no details
- % coverage: no details
- Type of wrap if used: polyethylene
REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance 'removed' after exposure
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4, 8 and 16 ml/kg bw (no further details).
- Concentration (if solution): neat - Duration of exposure:
- 24 h
- Doses:
- 4, 8 and 16 ml/kg bw
- No. of animals per sex per dose:
- 4 males/dose
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no details
- Necropsy of survivors performed: apparently yes - very limited details given
- Other examinations performed: body weight - very limited details given - Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 11.3 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 5.19 - < 24.7
- Remarks on result:
- other: equivalent to 11526 mg/kg bw based on density of 1.02
- Mortality:
- See table 1.
- Clinical signs:
- other: None reported.
- Gross pathology:
- See table 1; no further details given.
- Other findings:
- - Organ weights: not measured
- Histopathology: see table 1
- Potential target organs: insufficient detail available - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, the concluded LD50 value was 11.3 ml/kg bw in male and female rabbits (equivalent to 11526 mg/kg bw based on density of 1.02).
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.1100 (Acute Dermal Toxicity)
- Version / remarks:
- [as stated in SIAR, 2003; not evident from study report seen by this reviewer]
- GLP compliance:
- not specified
- Remarks:
- SIAR (2003) notes that this laboratory was GLP certified at the date of this study
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no details given
- Age at study initiation: no details given
- Weight at study initiation: 2-3 kg
- Fasting period before study: no
- Housing: no details given
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated
ENVIRONMENTAL CONDITIONS
no details given
IN-LIFE DATES: no details given - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: no details
- Type of wrap if used: impervious wrap covered by Vetrap bandage tape
REMOVAL OF TEST SUBSTANCE
excess liquid removed - no further details
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied: 1, 2, 4 or 8 ml/kg bw
- Concentration: neat
- Constant volume: no - Duration of exposure:
- 24 h
- Doses:
- 8, 4, 2, and 1 ml/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily for 14 days; body weights on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, microscopic examination of limited range of tissues - Statistics:
- Moving average method (Thompson, 1947; Weil, 1983)
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 4.29 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 2.9 - < 6.34
- Remarks on result:
- other: equivalent to 4076 mg/kg bw based on density of 0.95
- Mortality:
- Among groups of males and groups of females, 5/5 and 2/5 died at 8 and 4 ml/kg bw, respectively. There were no deaths at the lower doses of 1 and 2 ml/kg bw. See table 1.
- Clinical signs:
- other: General signs of toxicity included sluggishness, prostration and diarrhoea. Blood loss around the rectal and urogenital areas were also widespread. See table 1.
- Gross pathology:
- Treatment-related chages were detected in the following organs: kidney, lungs, liver, stomach, urinary bladder and urethra (see table 2). The kidney was identified as the target organ.
- Other findings:
- Microscopic examinations (on 2 rabbits/sex for the upper dose groups, 1/sex for the lower dose groups) identified acute renal necrosis in those that died (at 8 and 4 ml/kg bw) with accompanying tubular proteinosis and necrosis or other changes to gastric mucosa. Only mild kidney changes were reported in those of the 4 ml/kg bw groups that survived. No clear treatment-related effects were identified in the urinary bladder. Skin changes were seen in all treated groups, from acute necrotic changes in those that died to inflammation and vascular changes in survivors.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1100 (Acute Dermal Toxicity) and in compliance with GLP, the concluded LD50 value was 4.29 ml/kg bw in male and female rabbits (equivalent to 4076 mg/kg bw based on density of 0.95).
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 14 August 1990 to 28 August 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- 1987
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: The test substance was administered undiluted.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not specified
- Preliminary purification step (if any): not specified
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable - Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Langshaw Farms, Augusta, Michigan
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: young, no further information given
- Weight at study initiation: 2.2 - 2.6 kg
- Fasting period before study: none
- Housing: Housed individually in clean, stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: dorsal area
- % coverage: 10%
- Type of wrap if used: porous gauze dressing
REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with tap water
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw, volume not specified
- Constant volume or concentration used: yes
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg kg/bw
- No. of animals per sex per dose:
- 5
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently after dosing, then twice daily thereafter. All rabbits were weighed at 1, 7 and 14 days after the application of the test material.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Statistics:
- Not used.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths occurred during the study period.
- Clinical signs:
- other: No clinical signs of toxicity occurred during the study period.
- Gross pathology:
- All animals had changes in skin and changes were not uniformly distributed in the dermal test site. The distribution of skin changes strongly suggest causation by mechanical trauma of handling and/or restrained of the animals.
- Other findings:
- - Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined
: - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study, conducted according to OECD Test Guideline 402 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg bw was concluded.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: RCC Ltd., Switzerland
- Age at study initiation: males 9 weeks, females 12 weeks
- Fasting period before study: not reported
- Housing: During acclimation, in groups of 5/sex in Makrolon type 4 cages. Individually in Makrolon type-3 cages during treatment and observation.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 'Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for htis study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: the back
- % coverage: 10
- Type of wrap if used: Semi-occlusive dressing was wrapped around the abdomen, and fixed with an elastic adhesive bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg bw - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 males, 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and viability were observed once daily during acclimatization period and 1, 2, 3 and 5 hours after test item administration on test day 1 and twice daily during days 2-15. Each animal was examined for changes in appearance and behaviour once daily during the acclimatization phase. 1, 2, 3 and 5 hours after test item administration on test day 1, and once daily during days 2-15. All abnormalities were recorded. Body weights were recorded on days 1, 8 and 15.
- Necropsy of survivors performed: yes - Statistics:
- No statistical analysis was used.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths occurred during the study.
- Clinical signs:
- other: Reversible slight to moderate reddening (maculated), scaling, and scabbing were noted at the application in 6, 2 and 3 animals respectively. All dermal reactions subsided by day 10. No other clinical signs were observed during the observation period.
- Gross pathology:
- No macroscopic findings were observed at necropsy.
- Other findings:
- None reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the acute dermal toxicity study, conducted according to OECD Test Guideline 402 and in compliance with GLP, the concluded LD50 value was >2000 in male and female rats.
Referenceopen allclose all
10 ml/kg is calculated to be 9500 mg/kg using the formula
mg/kg = ml/kg*density*1000, where density = 0.95
Table1. Number of animals dead and with evident toxicity
Dose (mg/kg bw) |
Mortality dead/total) |
Number with evident toxicity (/total) |
||||
Male |
Female |
Combined |
Male |
Female |
Combined |
|
2007 |
0/5 |
0/5 |
0/10 |
0/5 |
0/5 |
0/10 |
Table 1: Number of animals dead and with evident toxicity, and time range within which mortality occurred
Dose |
Mortality (# dead/total) |
Time range of deaths (days) |
Local skin effects |
Pathology |
Body weight change (g) [as reported – initial body weight not given] |
4 |
0/2 |
- |
Scabbing in1 of 2 on day 14 |
In fatalities: discoloured liver (mottled red and tan, white spots) and kidneys (tan). In survivors: discoloured livers (dark red) and kidneys (mottled tan and red). |
4; 61 |
8 |
1/4 |
9 |
Erythema, oedema, desquamation and necrosis; full details not presented. |
-784 to 239 (mean 239) |
|
16* |
3/4 |
1, 2, 4 |
Erythema, oedema, desquamation, necrosis and fissuring in the survivor; full details not presented. |
59 |
* two different samples of test substance used for 2 rabbits in each case
Table 1: Number of animals dead and with evident toxicity, and time range within which mortality occurred
Dose |
Mortality (dead/total) |
Time range of deaths (days) |
Number with evident toxicity |
|||
Male |
Female |
Combined |
Male |
Female |
||
1 |
0/5 |
0/5 |
0/10 |
- |
1/5: substantial bleeding around rectal area on day 1, recovery on day 2 |
1/5: diarrhoea on day 1, recovery on day 2 |
2 |
0/5 |
0/5 |
0/10 |
- |
1/5: substantial bleeding around rectal area on day 1, recovery on day 4 |
2/5: substantial bleeding around rectal area on day 1. 1/5: sluggishness on day 1. Recovery on day 2 |
4 |
2/5 |
2/5 |
4/10 |
2-3 |
Victims: 2/2 sluggish, unsteady gait; 1/2 mucus around rectal area, mucus and blood clots under cage on day 2 Survivors: sluggish on day 1. 2/3 had rectal blood loss on day 1. Recovery on days 2-3. |
Victims: 2/2 sluggish, blood loss around rectal and vaginal areas on day 1. 1/2 unsteady gait, diarrhoea on day 2 Survivors: sluggishness and blood loss from rectum on day 1. Blood under cage on day 2. 1/3 was emaciated on day 7. Recovery of 2 survivors on day 3. |
8 |
5/5 |
5/5 |
10/10 |
1-2 |
Sluggishness, prostration, blood loss from urogenital or rectal areas, or salivation. |
Sluggishness, prostration, unsteady gait or perianal discharge. |
Table 2: Effect on body weight and gross pathology
Dose |
Mean body weight (kg) (days 0/7/14) |
Gross Pathology |
||
Male |
Female |
Male |
Female |
|
1 |
2.5/2.6/2.8 |
2.5/2.6/2.8 |
No remarkable findings |
No remarkable findings |
2 |
2.7/2.6/2.8 |
2.4/2.4/2.6 |
Lungs (2/5) dark red or pink |
No remarkable findings |
4 |
2.6/2.2/2.4 |
2.8/2.3/2.6 |
Victims: lungs (1/2) dark red; stomach (2/2) discoloured; kidney (1/2) haemorrhaged; bladder (1/2) dark red clots; liver (1/2) mottled tan Survivors: lungs mottled or with dark red foci |
Victims: lungs (1/2) bright red; stomach (1/5) areas adhered to walls; kidneys haemorrhaged; Urinary bladder (2/2) filled with red liquid; urethra (1/2) haemorrhaged; Survivors: lungs dark red or mottled |
8 |
2.4/-/- |
2.4/-/- |
Lungs (2/5) bright red, mottled; livers mottled tan; stomachs with haemorrhage (1/5) or mucus (2/5); kidneys haemorrhaged (1/5) or tan (2/5); urinary bladder (2/5) filled with red liquid. |
Lungs mottled red or pink; livers (2/5) mottled tan; stomachs with mucus; kidneys (1/5) tan. |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Additional information
The registered substance trimethoxy(methyl)silane and its reaction products with 3-aminopropyltriethoxysilane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane is a UVCB substance. The identity and concentration range of the constituents have been determined by GC analysis. A detailed description of the composition can be found in Section 1.2 of IUCLID. There are no acute toxicity data for the registered substance, therefore, data for its constituents have been used for acute oral, inhalation and dermal toxicity endpoints (summarised in Table 1) making it possible to determine the appropriate classification of the substance based on the rules for mixtures specified in Regulation (EC) No 1272/2008.
Table 1 Summary of acute toxicity data for constituents of the registered substance
Block |
Chemical Name |
CAS Number |
Acute oral LD50 (mg/kg bw/day) |
Acute inhalation LC50 (mg/l) |
Acute dermal LD50 (mg/kg bw/day) |
A |
Trimethoxy(methyl)silane |
1185-55-3 |
11685 |
>42.1 |
>9500 |
A |
Triethoxy(methyl)silane |
2031-67-6 |
>2007 |
>13.5 |
>2007 |
B |
3-Aminopropyl(trimethoxy)silane |
13822-56-5 |
3030 |
- |
11526 |
B |
3-Aminopropyl(triethoxy)silane |
919-30-2 |
1490-2690 |
- |
4080 |
701 -408 -8 |
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine |
None |
>2000 |
|
>2000 |
HP for D |
N-ethyl-3-trimethoxysilyl-2-methyl-propanamine |
227085-51-0 |
>2000 |
- |
>2000 |
Block A
Trimethoxy(methyl)silane (CAS 1185-55-3)
In the acute oral toxicity study with trimethoxy(methyl)silane, conducted prior to OECD Test Guidelines and GLP, an LD50 value of 12.3 ml/kg (equivalent to 11685 mg/kg bw based on density of 0.95) was determined for male rats (Mellon Institute, 1963). In the study 5 male rats were given a single oral gavage administration of 16 and 8 ml undiluted test material/kg. Following administration, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. Most deaths occurred within the first several hours after dosing. Clinical signs of toxicity were sluggishness and unsteady gait post-dosing. All surviving animals showed body weight gains. At necropsy, gross examination revealed congested lungs, mottled livers with prominent acini and some haemorrhage and congestion of the gastrointestinal tract.
In the acute inhalation toxicity study with trimethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value was >7605 ppm (equivalent to 42.1 mg/l) in rats (Dow Corning Corporation, 2006). In the study 5 male and 5 female rats were exposed for 6 hours to the test material vapours at concentration of 7605 ppm (analytical) by whole body inhalation. Following exposure, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No mortality was observed during the observation period. Clinical signs of toxicity included urine staining, discoloured urine, faecal staining, head and muzzle soiling, with all females returning to normal by post exposure day 4. Necropsy findings included urinary bladder calculi and kidney foci in both sexes, an enlarged kidney in one male, and abscessed prostate glands in two males. Urinary tract and prostate disease were attributed to urolithiasis of uncertain primary aetiology; a direct role for the test article in the formation of urinary calculi could neither be confirmed nor disproven as a result of this study.
In the acute dermal toxicity study with trimethoxy(methyl)silane, conducted according to a protocol similar to OECD Test Guideline 402 but prior to GLP, the LD50 value was >10 ml/kg (equivalent to 9500 mg/kg bw based on density of 0.95) in rabbits (Mellon Institute, 1963). In the study 4 rabbits (sex unspecified) were subject to a single 24-hour dermal application of 10 ml/kg bw undiluted test material under occlusive dressing. The animals were observed for signs of toxicity for 14 days. Necropsy was performed at the end of the study. No deaths occurred throughout the observation period. Little skin irritation was observed but some desquamation was found after 14 days. There were no findings at necropsy.
The substance is a part of Block A. It also shares a common silanol hydrolysis product, methylsilanetriol, with the second Block A constituent triethoxy(methyl)silane (CAS 2031-67-6).
Triethoxy(methyl)silane (CAS 2031-67-6)
In the acute oral toxicity study with triethoxy(methyl)silane, conducted in according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, there was no mortality or marked systemic effect in rats and the LD50 value was concluded to be 2007 mg/kg bw (Hazleton France, 1992a). In the study male and female rats were given a single oral gavage administration of 2007 mg undiluted test material/kg bw. Following administration, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No deaths occurred throughout the study. Subdued behaviour in all treated animals was observed at 1, 2 and 4 hours post-dosing and no overt clinical effects were observed at Day 2. There were no remarkable macroscopic findings.
In the acute inhalation (aerosol) toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value was >13.5 mg/l (Hoechst, AG., 1991). In the study 5 male and 5 female rats were subject to a single 4-hour nose only inhalation exposure to the test substance aerosol at concentration of 13.5 mg/l. Following exposure, the animals were observed for 14 days for clinical signs of toxicity. Necropsy was performed at the end of the observation period. Only one male rat died, while all the other animals survived until the end of the study period. Ataxia, irregular respiration, stupor, altered gait, prostration, tonic convulsions, trembling and reduced spontaneous activity were seen in both sexes during the 14-day observation period. Dark red and patchy lungs were seen in the one male rat that died.
In the acute dermal toxicity study with triethoxy(methyl)silane, conducted according to OECD Test Guideline 402 and in compliance with GLP, the LD50 value was >2007 mg/kg bw (Hazleton France, 1992b). In the study male and female rats were subject a single 24-hour dermal application of 2007 mg undiluted test material/kg bw. Following the application, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No deaths occurred throughout the study. There were no clinical signs of toxicity. There were no abnormal macroscopic findings.
The substance is a part of Block A. It also shares a common silanol hydrolysis product, methylsilanetriol, with the first Block A constituent trimethoxy(methyl)silane (CAS 1185-55-3).
Block B
3-Aminopropyl(triethoxy)silane (CAS 919-30-2)
In the acute oral toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1175 (Acute Oral Toxicity) and in compliance with GLP, the LD50 values for female and male rats were 1.57 and 2.83 ml/kg bw, respectively (Bushy Run Research Center, 1989). In the study 5 male and 5 female rats were given a single oral gavage administration of undiluted test material at 4, 2, and 1 ml/kg bw in males and 2, 1.41 and 1 ml/kg bw in females. Following administration, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. Deaths occurred at 1.41 (1/5) and 2 ml/kg bw (5/5) in females and at 4 (4/5) and 2 ml/kg bw (1/4) in males. No deaths occurred in either sex at 1 ml/kg bw. Sluggishness, lacrimation, kyphosis (curvature of the thoracic spine), piloerection and red encrusted fur around nose was seen in males at 4 ml/kg bw. Survivor recovered at 3 days. Sluggishness, unkempt appearance, periurogenital brown staining, red encrusted fur around nose and eyes, closed eyelids, emaciation and diarrhoea were seen in males at 2 ml/kg bw. Survivors recovered at 5 to 9 days. All females that died at 2 ml/kg bw showed signs of sluggishness, lacrimation, unkempt appearance, red encrusted fur around nose and eyes and diarrhoea. The females at 1.41 ml/kg bw showed signs of sluggishness, periurogenital staining (positive for blood), red encrusted fur around nose; survivors recovered at 2 days. Females at 1 ml/kg bw showed only signs of sluggishness post-dosing, but fully recovered by day 2. Gross and microscopic examination revealed kidney damage, particularly in decedents.
In the acute inhalation toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to OECD Test Guideline 403 and in compliance with GLP. The LC50 values were >5 and 16 ppm, for male and female rats, respectively (Bushy Run Research Center, 1989). In the study 5 male and 5 female rats were subject to a single 6-hour whole body inhalation exposure to the saturated vapour concentration of the test material. The mean measured concentrations of the test material (after hydrolysis) were 5 and 16 ppm, for male and female rats, respectively. Following exposure, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No death occurred during the study. No clinical signs were evident during the 14-day study period. No macroscopic findings were observed at necropsy.
In the acute dermal toxicity study with 3-aminopropyl(triethoxy)silane, conducted according to EPA OTS 798.1100 (Acute Dermal Toxicity) and in compliance with GLP, the LD50 value was 4.29 ml/kg bw in male and female rabbits (equivalent to 4076 mg/kg bw based on density of 0.95) (Bushy Run Research Center, 1989). In the study 5 male and 5 female rabbits were subject to a single 24-hour dermal application of undiluted test material at doses of 8, 4, 2, and 1 ml/kg bw. Following application, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. Among the males and females, 5/5 and 2/5 died at 8 and 4 ml/kg bw, respectively. There were no deaths at the lower doses of 1 and 2 ml/kg bw. General signs of toxicity included sluggishness, prostration and diarrhoea. Blood loss around the rectal and urogenital areas were also widespread. Treatment-related changes at necropsy were detected in the following organs: kidney, lungs, liver, stomach, urinary bladder and urethra. The kidney was identified as the target organ.
The substance is a minor constituent of the registered substance, part of Block B. It also shares a common silanol hydrolysis product, 3-aminopropylsilanetriol, with the other Block B constituent 3-(trimethoxysilyl)propylamine (CAS 13822-56-5).
3-(Trimethoxysilyl)propylamine (CAS 13822-56-5)
In the acute oral toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 but pre-GLP compliance, the LD50 value was 2.97 ml/kg bw (equivalent to 3030 mg/kg bw based on density of 1.02) (Bushy Run Research Center, 1980). In the study 5 male rats were given a single oral gavage administration of 1.25, 2.5, 5.0 ml undiluted test material/kg bw. Following administration, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. Deaths occurred at 5 ml/kg bw (4/5) and 2.5 ml/kg bw (2/5). No animals died at 1.25 ml/kg bw. The observed clinical signs included sluggishness and unsteady gait. Among the survivors at 2.5 ml/kg bw, pus in the lungs was seen in one animal. No other remarkable findings were noted in the survivors. The animals that died had purple colouration in the glandular stomach.
In the acute dermal toxicity study with 3-(trimethoxysilyl)propylamine, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, the LD50 value was 11.3 ml/kg bw in male and female rabbits (equivalent to 11526 mg/kg bw based on density of 1.02) (Bushy Run Research Center, 1980). In the study 4 male rabbits were subject to a single 24-hour dermal application of undiluted test material at doses of 4, 8 and 16 ml/kg bw. Following application, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. At 16 ml/kg bw 3/4 animals died, while 1/4 died at 8 ml/kg bw. No clinical signs of toxicity were reported, but severe local effects were observed at the higher dose levels of 8 and 16 ml/kg. In fatalities, necropsy findings were discoloured liver (mottled red and tan, white spots) and kidneys (tan). In survivors, discoloured livers (dark red) and kidneys (mottled tan and red).
The substance is a minor constituent of the registered substance, part of Block B. It also shares a common silanol hydrolysis product, 3-aminopropylsilanetriol, with the other Block B constituent 3-aminopropyl(triethoxy)silane (CAS 919-30-2).
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine (EC No. 701 -408 -8)
In the key acute oral toxicity study with trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg bw was concluded (Dow Corning Corporation, 1990a). Following a single oral gavage administration of 2000 mg/kg bw undiluted test material to 5 male and 5 female rats, no test substance-related mortality, clinical signs of toxicity or body weight changes occurred. There were no gross macroscopic abnormalities noted. One female died prior to end of the observation period and its death was attributed to the gavage procedure.
In the key acute dermal toxicity study with trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine, conducted according to OECD Test Guideline 402 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg bw was concluded (Dow Corning Corporation, 1990b). Following a 24-hour dermal application of 2000 mg/kg bw undiluted test material to the dorsal area of 5 male and 5 female rabbits, no test substance-related mortality, clinical signs of toxicity or body weight changes occurred. Additionally, no gross macroscopic abnormalities were noted.
This source substance is the methoxy analogue of the registered methoxy/ethoxy substance (target). Acute toxicity studies for this analogue are included to cover Blocks C to G, and unspecified minor constituents, for which there are no acute toxicity data. The only difference between the target and source substances is one of the three starting materials. The source substance has a starting material, 3-aminopropyl(trimethoxy) silane [237-511-5, 13822-56-5] and the target has the starting material that is the triethoxy analogue, 3-aminopropyl(triethoxy)silane [213-048-4, 919-30-2]. Therefore, the target substance has additional ethoxy constituents. However, whether ethoxy or methoxy, the target and source substance constituents hydrolyse to the same respective silanol hydrolysis products. The only difference is the non-silicon hydrolysis product; the target releases methanol and ethanol, whereas the source substance releases methanol only. The small molecule alkoxysilanes of Block A, Block B and those of Block U1 have similar physicochemical properties as the starting materials. Together they constitute about 60-70% of the substance. Blocks C-G and U2 constitute approximately 20-30% of the substances. These are oligomers formed by combination of the monomer starting materials. Under acidic conditions (pH <4) as experienced in the stomach and relevant to oral studies, the hydrolysis of the source and target substances is rapid and will form the same hydrolysis products.
Table 2: Names of the Blocks in the Source substance (Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine; EC No. 701 -408 -8)
Block |
Chemical Name |
EC |
CAS |
Mol Wt |
Range |
A |
Trimethoxy(methyl)silane |
214-685-0 |
1185-55-3 |
136.22 |
40-60% |
B |
3-aminopropyl(trimethoxy) silane |
237-511-5 |
13822-56-5 |
179.29 |
5-10% |
C |
Disilyl(cycloalkylamine), penta(methoxy)- |
None |
None |
383.59 to 473.75 |
10-20% |
D |
Trisilyl(alkylamine), octamethoxy-methyl- |
None |
None |
519.82 to 609.97 |
5-15% |
E |
Tetrasilyl(alkylamine), decamethoxy-methyl- |
None |
None |
724.12 |
0-5% |
F |
Pentasilyl(alkylamine), tridecamethoxy-methyl- |
None |
None |
860.34 |
0-5% |
G |
Methyl(methoxy) functional disiloxanes |
None |
None |
226.38 to 269.45 |
0-2% |
U1 |
Unspecified Silane Substances where each constituent is less than 1% |
None |
None |
|
0-2% |
U2 |
Unspecified Silyl Substances where each constituent is less than 1% |
None |
None |
>500 |
0-5% |
H1 |
Methanol |
67-56-1 |
200-659-6 |
32.07 |
0-10% |
Table 2: Names of the Blocks in the Target substance (trimethoxy(methyl)silane and its reaction products with 3-aminopropyltriethoxysilane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane)
Block |
Chemical Name |
EC |
CAS |
Mol Wt Range |
Range |
A |
Triethoxy/methoxy(methyl)silane |
214-685-0 217-983-9 |
1185-55-3 2031-67-6 |
136.22 to 178.31 |
50-70% |
B |
3-aminopropyl-tri(ethoxy/methoxy) silane |
237-511-5 213-048-4 |
13822-56-5 919-30-2 |
179.29 to 207.35 |
0-10% |
C |
Disilyl(cycloalkylamine), penta(ethoxy/methoxy)- |
None |
None |
383.59 to 439.70 |
5-20% |
D |
Trisilyl(alkylamine), octa(ethoxy/methoxy)-methyl- |
None |
None |
519.82 to 603.98 |
5-20% |
E |
Tetrasilyl(alkylamine), deca(ethoxy/methoxy)-methyl- |
None |
None |
738.14 to 780.23 |
0-5% |
F |
Pentasilyl(alkylamine), trideca(ethoxymethoxy)-methyl- |
None |
None |
860.34 to 940.47 |
0-5% |
G |
Methyl(ethoxy/methoxy) functional disiloxanes |
None |
None |
226.38 to 240.41 |
0-2% |
U1 |
Unspecified Silane Substances where each constituent is less than 1% |
None |
None |
|
0-1% |
U2 |
Unspecified Silyl Substances where each constituent is less than 1% |
None |
None |
>500 |
0-5% |
H1 |
Methanol |
67-56-1 |
200-659-6 |
32.07 |
0-10% |
H2 |
Ethanol |
64-17-5 |
200-578-6 |
46.07 |
0-5% |
Block D
N-ethyl-3-trimethoxysilyl-2-methyl-propanamine (CAS 227085-51-0)
The acute oral toxicity study with N-ethyl-3-trimethoxysilyl-2-methyl-propanamine, conducted according to OECD Test Guideline 423 and in compliance with GLP, the LD50 value was concluded to be >2000 mg/kg bw (RCC, 2001a). In the study 3 male and 3 female rats were given a single oral gavage administration of undiluted test material at 2000 mg/kg bw. Following administration, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No death occurred during the study. In one female, ruffled fur and hunched posture were noted on test day 1. No clinical signs were evident from test day 2 until the end of the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.
In the acute dermal toxicity study with N-ethyl-3-trimethoxysilyl-2-methyl-propanamine, conducted according to OECD Test Guideline 402 and in compliance with GLP, the LD50 value was >2000 in male and female rats (RCC, 2001b). In the study 5 male and 5 female rats were subject to a single 24-hour dermal semi-occlusive application of the undiluted test material at doses of 2000 mg/kg bw. Following application, the animals were observed for 14 days for signs of toxicity. At the end of the 14-day observation period, necropsy was performed on the surviving animals. No deaths occurred during the study. Reversible slight to moderate reddening (maculated), scaling, and scabbing were noted at the application site in 6, 2 and 3 animals, respectively. All dermal reactions subsided by day 10. No other clinical signs were observed during the observation period. No macroscopic findings were observed at necropsy.
Data on this substance are relevant as its silanol hydrolysis product is an analogue of the hydrolysis product of constituents trisilyl(alkylamine), octa(ethoxy/methoxy)-methyl- in Block D. Therefore, data on this substance are included as supporting data for completeness.
Conclusion for acute toxicity
It can be seen from the data summarised above that the only constituent that meets the criteria for acute toxicity classification is 3-aminopropyl(triethoxy)silane (CAS 919-30-2), which is classified for acute toxicity Category 4 (oral) in Annex VI of Regulation (EC) No 1272/2008.
Given that the concentration of this constituent in the registered substance (0 to 10%), it does not contribute towards the overall classification according to the rules for mixtures specified in Regulation (EC) No 1272/2008.
For other simple alkoxy and aminofunctional alkoxy constituents with no available data, it can be assumed that these are also not classified for acute toxicity based on weight of evidence for a number of alkyl and amino alkoxysilanes for which measured data indicate no significant differences in acute toxicity properties between methoxy and ethoxy analogues containing the same alkyl or amine groups attached to silicon. Further details of the available data are given in supporting reports attached in Section 13 of IUCLID (PFA, 2013t and PFA, 2013v).
For the trisilane and cyclo-trisilane constituents, no measured data are available for the parent materials. However, these hydrolyse very rapidly, particularly following oral exposure (see Section 4.1), to silanols, methanol and ethanol. In view of the high molecular weight of these parent constituents (>500) it is not anticipated that these would be more hazardous than the simple amino alkoxysilanes or corresponding silanols and it is therefore assumed for the purposes of assessment that these would not contribute to the overall classification of the registered substance for acute systemic toxicity. This conclusion is supported by measured data on trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine, which is not classified for acute toxicity via any route.
This substance the methoxy analogue of the registered methoxy/ethoxy substance (target). Acute toxicity studies for this analogue are included to cover Blocks C to G, and unspecified minor constituents, for which there are no acute toxicity data.
Justification for classification or non-classification
Based on the available data for the constituents of trimethoxy(methyl)silane and its reaction products with 3-aminopropyltriethoxysilane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, no classification for acute oral, dermal or inhalation toxicity is required according to the rules for mixtures specified in Regulation (EC) No 1272/2008.
The only constituent for which any acute toxicity classification is required is 3-aminopropyl(triethoxy)silane (CAS 919-30-2) which is classified for acute toxicity Category 4 (oral) in Annex VI of Regulation (EC) No 1272/2008. At a concentration ranging from 0 to 10 % in the registered substance, this constituent does not contribute towards the overall classification of the substance.
Since methanol is present in the registered substance at concentration ranging from 0 to 10%, classification STOT SE 2 (eyes and central nervous system) is required for the registered substance according to Annex VI of Regulation (EC) No 1272/2008.
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