Registration Dossier

Administrative data

Description of key information

The key acute oral toxicity study conducted according to a protocol similar to the now deleted OECD Test Guideline 401, however, not in compliance to GLP, reports an LD50 of 8025 mg/kg bw (Dow Corning corporation, 1976).

The key acute inhalation study which was conducted according to OECD Test Guideline 403 and in compliance with GLP, reports an LC50 of >5300 mg/m3 (>5.3 mg/l) (Allied Corporation, 1982).

The key acute dermal study which was pre-guideline and pre-GLP, however, similar to OECD Test Guideline 402, reports an LD50 was 4250 mg/kg bw (Mellon Institute, 1962).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Weighing and necropsy of animals were not performed.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No necropsies and no weighing of animals.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 200 ± 2g
- Fasting period before study: Overnight
- Housing: Grid floor cages (segregated according to sex and dose)
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: No data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 12.6 ml/kg bw
Doses:
3.9, 5.0, 6.3, 10.0 and 12.6 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: Observed daily. Animals do not appear to have been weighed.
- Necropsy of survivors performed: no
Statistics:
LD50 and 95% confidence limits calculated using the method of Litchfield, J.T. and Wilcoxon, F. (1949) J. Pharm Exp Therap. 96. 99.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
7.5 mL/kg bw
95% CL:
>= 6 - <= 9.37
Remarks on result:
other: Assuming a density of 1.07g/cm3 this gives an LD50 of 8025 mg/kg bw
Mortality:
See Table 1.
Clinical signs:
Piloerection and lethargy within one hour of administration, followed by coma and death. All deaths occurred within 48 hours of administration and all survivors were generally asymptomatic after this time.
Body weight:
Not measured.
Gross pathology:
Not examined.
Other findings:
None reported.

Table 1 Summary of mortality data.

 Dose ml/kg       Cumulative deaths by day (/10)  Percentage mortality
   1  2  3  4  7  14  
 12.6  5  8  8  8  8  8  80
 10.0  7  7  7  7  7  7  70
 6.3  3  3  3  3  3  3  30
 5.0  3  3  3  3  3  30
 3.9  1  1  1  1  1  1  10
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study (reliability 2), that was conducted using a protocol similar to the now deleted OECD 401 (animals not weighed and no necropsies performed), but not to GLP, the LD50 for gamma-glycidyloxypropyltrimethoxysilane was 7.5 ml/kg bw (assuming a density of 1.07 g/cm3 this gives an LD50 of 8025 mg/kg bw).
Executive summary:

In an acute oral toxicity study (reliability 2) that was conducted using a protocol similar to the now deleted OECD 401 (animals were not weighed and no necropsies were performed), but not to GLP, the LD50 for gamma-glycidyloxypropyltrimethoxysilane was 7.5 ml/kg bw (assuming a density of 1.07g/cm3 this gives an LD50 of 8025 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
8 025 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01.12.1981 to 17.12.1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, New York.
- Age at study initiation: 9-11 weeks
- Weight at study initiation: Not defined
- Fasting period before study: No data
- Housing: Individually in suspended wire mesh-bottom exposure cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Four weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71-73 (22-23 °C) 
- Humidity (%): 69-78
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 01.12.1981 To: 17.12.1981
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass exposure chamber.
- Exposure chamber volume: 225 litre.
- Method of holding animals in test chamber: none
- Source and rate of air: Room air. Flow rate of 50 l/minute.
- Method of conditioning air: No data.
- System of generating particulates/aerosols: Spraying Systems 1/4 (?) J Nebulizer.
- Method of particle size determination: cascade impaction.
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Temperature (°F): 71-73 (22-23 °C); Humidity (%): 69-78.


TEST ATMOSPHERE
Mass median aerodynamic diameter was determined hourly by cascade impaction for each exposure level and ranged from 1.4 to 2.0 microns.  
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric methods and gas chromatography (considered secondary due to recovery inefficiencies, however, gas chromatographic values averaged 85% of the gravimetrically determined concentrations).
Duration of exposure:
4 h
Concentrations:
0.8, 1.9, and 5.3 mg/L
No. of animals per sex per dose:
30
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations. Weighing on 1, 2, 4 or 5, 7 and 14 days after exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: gross necropsy.

Statistics:
No details.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.3 mg/L air
Exp. duration:
4 h
Mortality:
No deaths occurred at the two lower concentrations (1.9 and 0.8 mg/L).  At the highest concentration (5.3 mg/L), three rats died, one male on day 1, one female on day 1 and one female on day 2. 
Clinical signs:
other: Following exposures, all rats exhibited varying amounts of test substance contamination on the fur.  Clinical signs included excessive lacrimation, dry and moist rales, nasal discharge, and yellow staining in the anal-genital area.  These signs were consi
Body weight:
There was also a transient dose-related body weight depression seen in all groups (including the control) during the first week, however, mean body weights exceeded pre-exposure values by day 14 in all groups.
Gross pathology:
Discoloured lungs and autolytic changes were seen in the three rats that died.  There were no gross abnormalities noted at the necropsy of survivors.

Table of concentrations and particle sizing data of Prylog (mg/l and µm)

 Group  Method  Mean conc./mean MMD   Hourly air samples mg/l/MMD            Nominal conc.
       1  2  3  4  
 1  Analytical  4.8  4.0  4.9  5.2 4.9   25.3
   Gravimetric  5.3/1.9  5.7/2.0  5.4/1.8  5.4/1.8  4.7/1.8  
 2  Analytical  1.7  1.7  1.8  1.8  1.4  7.1
   Gravimetric  1.9/1.7  0.9/1.7  2.5/1.6  2.1/1.6  2.0/1.7  
 3  Analytical  0.6  0.7  0.6  0.6  0.6 2.3 
   Gravimetric  0.8/2.0  1.1/1.6  0.7/1.5  0.7/1.4  0.6/1.5   
               
Interpretation of results:
GHS criteria not met
Conclusions:
In a good quality acute inhalation study (reliability score 1) conducted to OECD 403, and GLP, an aerosol of unchanged Prylog (Silane, trimethoxy 3-(oxiranylmethoxy)propyl) gave an LC50 greater than 5.3 mg/l in rats.
Executive summary:

In a good quality acute inhalation study (reliability score 1) conducted to OECD 403, and GLP, an aerosol of unchanged Prylog (Silane, trimethoxy 3-(oxiranylmethoxy)propyl) gave an LC50 greater than 5.3 mg/l in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 300 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
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:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: 3-5 months
- Weight at study initiation: 2240 - 2730 grams
- Fasting period before study:
No further details available
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data
Duration of exposure:
24 hours
Doses:
2.5 and 5.0 ml/kg
No. of animals per sex per dose:
Four
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily. Weighed at the end of the observation period
- Necropsy of survivors performed: no data
- Other examinations performed: gross necropsy
Statistics:
LD50 calculated using moving average method.
Sex:
male
Dose descriptor:
LD50
Effect level:
3.97 mL/kg bw
95% CL:
>= 2.93 - <= 5.37
Remarks on result:
other: assuming a density of 1.07g/cm3 this gives an LD50 of 4248 mg/kg bw
Mortality:
Deaths occurred on the first and second days after application.
Clinical signs:
None reported.
Body weight:
All survivors gained weight during the observation period.
Gross pathology:
Congested lungs, mottled livers with prominent acini, and off-colour kidneys with internal congestion.
Other findings:
Erythema and slight necrosis were observed.
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified according to Regulation (EC) No. 1272/2008.
Conclusions:
In a pre-GLP, pre-guideline dermal irritation study (reliability score 2), conducted using a protocol comparable to OECD 402, the LD50 for glycidoxy propyltrimethoxysilane was 3.97 ml/kg bw (using a density of 1.07 g/cm3 this gives an LD50 of 4250mg/kg bw) in rabbits.
Executive summary:

In a pre-GLP, pre-guideline dermal irritation study (reliability score 2), conducted using a protocol comparable to OECD 402, the LD50 for glycidoxy propyltrimethoxysilane was 3.97 ml/kg bw (using a density of 1.07 g/cm3 this gives an LD50 of 4250 mg/kg bw) in rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 248 mg/kg bw

Additional information

The key study for acute oral toxicity was conducted using a protocol similar to the now deleted OECD Test Guideline 401 (animals not weighed and no necropsies performed), but which pre-dated GLP, reported an LD50 of 7.5 ml/kg bw (equivalent to 8025 mg/kg bw). Clinical signs included piloerection and lethargy within one hour of administration, followed by coma and death. All deaths occurred within 48 hours of administration and all survivors were generally asymptomatic after this time. Effects on body weight were not recorded and no necropsy was carried out (Dow Corning Corporation, 1976).

A supporting study is available for acute oral toxicity wherein no deaths were observed and therefore, an LD50 of >5ml/kg was reported (equivalent to 5350 mg/kg bw) (Dow Corning Corporation, 1976).

A study which was conducted in a similar way to OECD Test Guideline 401 and which pre-dated GLP, reported an LD50 of 8.4 g/kg (equivalent to 8400 mg/kg). The result was disregarded as the test was performed at the Industrial BioTest laboratory (Dow Corning Corporation, 1963). The result was disregarded as the test was performed at the Industrial BioTest laboratory.

A supporting study which was pre-guideline pre-GLP, however, meets generally accepted scientific principles, is in agreement with the other studies, and an LD50 of 22.6 ml/kg bw was reported (equivalent to 24 182 mg/kg bw) (Mellon, 1962).

A supporting acute oral toxicity study conducted using a protocol similar to the now deleted OECD Test Guideline 401 but not in compliance with GLP, reports an LD50 of 16 900 mg/kg bw in rats (Allied Corporation, 1978).

A reliability 4 acute oral toxicity study is also included in the data set and reports that the dose of 2000 mg/kg bw registered substance did not produce any signs of toxicity within 20 to 30 minutes of dosing (WIL 2000).

The key study for acute inhalation toxicity was conducted according to a test protocol that is comparable to OECD Test Guideline 403, and in compliance with GLP. The clinical signs included excessive lacrimation, dry and moist rales, nasal discharge and yellow staining in the anal genital area. The signs were considered to be dose related and were not generally observed during the second week following exposure. There was a transient dose-related body weight depression seen in all groups, including control animals during the first week, however, mean body weights exceeded pre-exposure values in all groups by day 14. Gross pathology findings included discoloured lungs and autolytic changes in three rats which died. There were no gross abnormalities noted at the necropsy of survivors. The LC50 was reported to be >5.3 mg/L air following a 4 hour whole body exposure to the aerosol of the test material (Allied Corporation, 1982).

In a supporting acute inhalation toxicity study which was not conducted according to any guideline and not in compliance with GLP, reported an LC50 of >2.7 mg/L following four hours exposure to the test substance (Dow Corning Corporation, no year).

A supporting acute inhalation toxicity study was also available which has reliability 4, is similar to OECD Test Guideline 403, however not in compliance with GLP. An LC50 of >0.56 mg/l was reported in rats (Mellon Institute of Industrial Research, 1962),

The key study for acute dermal toxicity was conducted according to a test protocol that is comparable to OECD Test Guideline 402, however, not compliant with GLP. An LD50 of 3.97 ml/ kg bw (equivalent to 4248 mg/kg bw) was reported. Furthermore, deaths occurred on the first and second days after application. Additionally, no clinical signs were reported. Moreover, all survivors gained weight during the observation period. Necropsy findings included congested lungs, mottled livers with prominent acini, and off-colour kidneys with internal congestion (Mellon, 1962).

Justification for classification or non-classification

Based on studies for the oral, inhalation and dermal routes, no classification is required for the acute toxicity of 3 -(2,3 -epoxypropoxy)propyltrimethoxysilane, in accordance with current Regulation (EC) No. 1272/2008.