[3-(2,3-epoxypropoxy)propyl]triethoxysilane

Endpoint summary

Description of key information

In an acute oral toxicity study, conducted according to OECD Test Guideline 401 and in compliance with GLP, the LD₅₀ for [3-(2,3-epoxypropoxy)propyl]triethoxysilane was >2000 mg/kg bw in rats (RCC, 1994). There were no clinical signs of toxicity.

In a good quality acute inhalation study (Allied Corporation, 1982) conducted according to OECD 403, and in compliance with GLP, an aerosol of unchanged Prylog (Silane, trimethoxy 3-(oxiranylmethoxy) propyl) gave an LC₅₀greater than 5.3 mg/l in rats.

In an acute dermal toxicity study, read-across from [3-(2,3-epoxypropoxy) propyl]silane (Mellon Institute, 1962), the LD₅₀was 4250 mg/kg bw for males only. There were no mortalities or clinical signs, but necropsy findings included congested lungs, mottled livers with prominent acini, and off-colour kidneys with internal congestion.

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:

18.08.1994 to 08.09.1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral 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: BRL, Biological Research Laboratories Ltd., Switzerland
- Age at study initiation: Males: 8 weeks; Females: 10 weeks
- Weight at study initiation: Males: 198.4 - 210.4 g; Females: 176.8-181.4 g
- Fasting period before study: yes
- Housing: Groups of five in Makrolon type IV cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ±2
- Humidity (%): 49-72
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25.08.1994 To: 08.09.1994

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15. Body weights were recorded on test day 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination only

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

No deaths occurred.

Clinical signs:

other: There were no clinical signs of toxicity.

Gross pathology:

No abnormal findings .

Other findings:

None

Interpretation of results:

not classified

Conclusions:

In an acute oral toxicity study conducted to OECD Test Guideline 401 and in compliance with GLP (reliability score 1) the LD50 for [3-(2,3-epoxypropoxy)propyl]triethoxysilane was >2000 mg/kg bw in rats.

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

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:

guideline study

Remarks:

The study was conducted according to an appropriate OECD/EU test guideline, and in compliance with GLP, and was considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified

Qualifier:

equivalent or similar to guideline

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 or test system 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:

Discolored 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:

not classified

Conclusions:

In a good quality acute inhalation study (reliability score 1) conducted to OECD 403, and in compliance with GLP, an aerosol of unchanged [3-(2,3-epoxypropoxy)propyl]trimethoxysilane gave an LC50 greater than 5.3 mg/l in rats.

Executive summary:

In a good quality acute inhalation study (reliability score 1) conducted according to OECD 403, and in compliance with GLP, an aerosol of unchanged [3-(2,3-epoxypropoxy)propyl]trimethoxysilane gave an LC50 greater than 5.3 mg/l in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 300 mg/m³ air

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

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 or test system 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

Mortality:

Deaths occurred on the first and second days after application.

Clinical signs:

other: None reported.

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:

not classified

Conclusions:

In a pre-GLP, pre-guideline dermal irritation study (reliability score 2), conducted using a protocol comparable to OECD 402, the LD50 for [3-(2,3-epoxypropoxy)propyl]trimethoxysilane 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 [3-(2,3-epoxypropoxy)propyl]trimethoxysilane was 3.97 ml/kg bw (using a density of 1.07 g/cm3 this gives an LD50 of 4250mg/kg bw) in rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 250 mg/kg bw

Additional information

There are no acute inhalation or dermal toxicity data for [3-(2,3-epoxypropoxy)propyl]triethoxysilane or its hydrolysis product, 2,3-dihydroxypropoxypropylsilanetriol, so good quality data for the related substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane have been used as read across. Justification of read-across is provided in the document attached in Section 13.

[3-(2,3-epoxypropoxy)propyl]triethoxysilane hydrolyses in contact with water (half-life predicted to be approximately 12-36 hours at pH 7), generating ethanol and 2,3-dihydroxypropoxypropylsilanetriol whereas the read across substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane hydrolyses faster (6.5 hours at pH 7) into 2,3-dihydroxypropoxypropylsilanetriol and methanol. At 37.5°C (relevant for inhalation exposure), the corresponding half-lives are 2.3 and 4 -13 hours, respectively (see Section 5.1.2). The registered substance and the read-across substance therefore generate a common silanol hydrolysis product, and ethanol and methanol, respectively. Ethanol and methanol are not acutely harmful to rats. For the purpose of assessing acute toxicity via the inhalation route by read across, the hydrolysis rate of both parent materials is similar enough in that the half-life exceeds the exposure time, therefore initial exposure is mainly to parent material.

In addition to the read across, a reliable acute toxicity oral study is available for the registration substance (RCC, 1994); the LD₅₀value is above 2000 mg/kg bw/day and showed no indication of significant clinical or systemic effects following a single dose, except at very high dose levels well in excess of the highest dose level in current guidelines for acute toxicity.

 

It is therefore considered appropriate to read-across acute inhalation and dermal data from the trimethoxy to the triethoxy analogue. Additional information is given in a supporting report (Peter Fisk Associates, 2013q), attached in Section 13 of the IUCLID dossier.

Justification for selection of acute toxicity – oral endpoint
The selected study is the only available acute oral toxicity study for the registered substance. It was conducted in accordance with an appropriate OECD Test Guideline 401 and in compliance with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The selected study is the only reliable acute inhalation study available for the most relevant surrogate substance. It was conducted in accordance with an equivalent OECD Test Guideline 406 and in compliance with GLP.

Justification for selection of acute toxicity – dermal endpoint
The selected study is the only reliable acute dermal toxicity study available for the most relevant surrogate substance. It pre-dated both OECD guidelines and GLP but was conducted according to a protocol that was similar to OECD 402.

Justification for classification or non-classification

Based on the available acute oral and read-across inhalation data [3-(2,3-epoxypropoxy)propyl]triethoxysilane is not classified for acute toxicity according to Regulation (EC) No 1272/2008.