Ethoxytrimethylsilane

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 > 2000 mg/kg bw

Inhalation (OECD 436), rat: LC50 > 20.57 mg/L

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:

3 Nov - 21 Dec 1995

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: 45 days (males), 56 days (females)
- Weight at study initiation: 191 - 200 g (males), 189 - 192 g (females)
- Fasting period before study: 16 h prior to application
- Housing: 2-3 animals per cage (Makrolon type III)
- Diet: ssniff R/M-H V 1530 (ssniff Spezialitäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55± 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: 2.67 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: no data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

First step: 3 males
Second step: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, at 5, 15, 30 and 60 min, as well as at 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days (once daily). Body weight was determined before administartion and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: Changes of skin and fur, eyes and mucous membranes, respiratory and circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern were observed at least once daily untl all symptoms subsided (afterwards each working day).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed after treatment with 2000 mg/kg bw.

Clinical signs:

other: No clinical signs of systemic toxicity were noted.

Gross pathology:

No organ abnormalities were observed at necropsy.

Table 1: Body weight and relative body weight gain of the animals in the acute oral toxicity study.

Dose group [mg/kg bw]		Bodyweight [g]			Bodyweight gain [%]
		start	after 7 d	after 14 d	day 1-7	day 1-14
2000	male	196.7	262.3	323.3	33.4	64.4
2000	female	190.3	216.0	234.3	13.5	23.1

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.

Conclusions:

In an acute oral toxicity study with ethoxy(trimethyl)silane (according to OECD 423, GLP compliant) a LD50 >2000 mg/kg bw was derived. Treatment of 3 male and 3 female Crj:CD(SD) rats with the limit dose of 2000 mg/kg bw provoked no mortality or clinical signs of toxicity. No effect on body weight gain was observed and no findings were reported at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

2017-04-18 to 2018-02-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

07 September 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

OGYÉI National Institute of Pharmacy and Nutrition, Budapest, Hungary, Budapest, Hungary

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: CRL:WI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Group 1: 8 weeks old; Group 2: 9 weeks old
- Weight at study initiation: Group 1: 299-334 g (males) and 220-231 g (females); Group 2: 347-389 g (males) and 223-238 g (females)
- Housing: 3 animals by sex per cage
- Diet: ssniff SM R/M “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” provided ad libitum
- Water: tap water provided ad libitum
- Acclimation period: 6 days (Group 1), 12 days (Group 2)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.7 – 26.4
- Humidity (%): 24 – 77
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany)
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. The flow of air through each port was at least 0.5 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: Vapour concentration was measured gravimetrically by adsorbent charcoal tube 17 times during each 4-hour exposure in both parts of the study.
- Samples taken from breathing zone: yes

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The starting dose level, 10 mg/L was chosen by the Sponsor as the toxicity of the test item was unknown at 20 mg/L.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

10.27 mg/L and 20.57 mg/L

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14-day observation period
- Frequency of observations and weighing: Clinical observations were performed on all animals during exposure at hourly intervals, following removal from restraint, approximately 1 hour after exposure, and daily for 14 days thereafter. Body weight was measured on Days 0 (before the exposure), 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were subject to a gross necropsy which included a detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

Statistics:

Not reported

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 20.57 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred in Group 1 when exposed to a test atmosphere concentration of 10.27 mg/L for 4 hours and 1 out of the 6 animals died in Group 2 when exposed to a test atmosphere concentration of 20.57 mg/L for 4 hours.

Clinical signs:

other: Group 1: In the male animals, laboured respiration (slight to moderate), noisy respiration (slight), prostration/prone position, decreased activity (extreme) and incoordination (slight) were recorded on Day 0. These animals were symptom-free from Day 1. I

Body weight:

Slight body weight losses, noted in all animals of both Group 1 and Group 2 on Day 0-1, were considered to be related to the restraint and exposure procedures. No marked body weight loss was observed during the experiment in the surviving animals between Day 1-14. Body weights were within the range commonly recorded for this strain and age.

Gross pathology:

No test item-related macroscopic observations were noted at a dose level of 10.27 mg/L. There was no evidence of any changes in the rats dosed at 20.57 mg/L. No specific cause of death was determined for the animal, which was found dead on Day 2. Collapsed lungs were observed at necropsy and considered to be the agonal or post mortem change.

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.

Conclusions:

In an acute inhalation toxicity study conducted according to OECD 436 and in compliance with GLP, the acute inhalation median lethal concentration (LC50) of ethoxy(trimethyl)silane in male and female Crl:WI rats was considered to be above 20.57 mg/L.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

> 20.57 mg/L air

Physical form:

inhalation: vapour

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

An acute oral toxicity study is available with ethoxy(trimethyl)silane (CAS 1825-62-3), which was conducted according to OECD 423 and in compliance with GLP (LPT, 2002). In a first step 3 male Crl:CD rats were treated with the limit dose of 2000 mg/kg bw. No mortality occurred and no clinical signs of systemic toxicity were noted. In accordance with the testing strategy supplied in OECD guideline 423 3 female animals were treated with 2000 mg/kg bw in the second step. Again no mortality and no clinical signs were observed. No findings after necropsy and no effects on body weight were observed in male and female animals. In conclusion a LD50 of >2000 mg/kg bw was derived.

Inhalation

An acute inhalation toxicity study is available with ethoxy(trimethyl)silane (CAS 1825-62-3), which was conducted according to OECD 436 and in compliance with GLP (Citoxlab, 2018). The test item was administered as vapour and the study was performed in two phases. The first exposure was performed at the target concentration of 10 mg/L on 3 animals of each sex (Group 1). Based on the results at this concentration, the second exposure was performed at the target concentration of 20 mg/L on 3 animals of each sex (Group 2). In both study phases, the animals were exposed to the test atmosphere for 4 hours using a nose-only exposure system.

No mortality occurred in Group 1 when exposed to a test atmosphere concentration of 10.27 mg/L for 4 hours and 1 out of the 6 animals died in Group 2 when exposed to a test atmosphere concentration of 20.57 mg/L for 4 hours. Clinical signs included prostration, with animals at the higher concentration being comatose but animals were symptom-free on Day 1 (Group 1) or Day 2 (Group 2). No marked body weight loss was observed during the experiment in the surviving animals between Day 1-14 and no test item-related macroscopic observations were noted at either dose level.

Based on these results, the acute inhalation median lethal concentration (LC₅₀) of ethoxy(trimethyl)silane in male and female Crl:WI rats was therefore considered to be above 20.57 mg/L.

Justification for classification or non-classification

The available data on acute oral and inhalation toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

No data on acute dermal toxicity are available.