Octamethyltrisiloxane

Endpoint summary

Description of key information

The key study for acute oral toxicity determined an LD₅₀value of >2000 mg/kg in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2004).  

The key study for acute inhalation toxicity exposed rats to a test atmosphere of vapour and determined an LC₅₀value of >22.6 mg/l (analytical) in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2004).

The key study for acute dermal toxicity determined an LD₅₀value of >2000 mg/kg in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009).

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

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)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CD (SD) IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: ca. 11 weeks
- Weight at study initiation: 220-241 g
- Fasting period before study: over night
- Housing: Individually housed in suspended wire mesh cages
- Diet: Lab diet 5002 Certified Rodent Diet, ad libitum, except the night prior to dosing and approximately 4 hours post-dosing
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 -22.2
- Humidity (%): 46-65
- Air changes (per hr): 10.2-11.3
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

3F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical abnormalities immediately after dosing and then approximately 30 minutes, 90 minutes, four hours post dose and daily thereafter. The animals were examined for a minimum of the following changes in the skin and fur, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, motor activity and behaviour pattern. The body weights were recorded on study day 0 prior to dosing, on study day 7 and on study day 14 prior to terminal sacrifice.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The gross necropsy included examination of the external surface, all orifices of the body and the cranial, thoracic and abdominal cavities and their contents.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: All animals appeared normal throughout the study.

Gross pathology:

No significant macroscopic findings were noted.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

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:

9 April 2004 - 23 June 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Mass median aerodynamic diameter / Geometric st. dev. not reported.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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

- Age at study initiation: 9 weeks at experimental start
- Weight at study initiation: females 199.4-208.2 g, males 295-310 g
- Housing: wire-mesh cages
- Diet: certified rodent chow, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: 7 days

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:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: 450 litres
- Method of holding animals in test chamber: The animals were positioned within stainless steel exposure caging specifically designed for use in the 450 litre chamber (two levels of 10 wire mesh cages).
- Source and rate of air: Nash Air Compressor (Model/Size: AL-574), air sourced from building air supply
- Method of conditioning air: Conditioned building air was passed through HEPA and activated charcoal filters before delivery to the chamber. The compressed air was passed through a series of filters to remove contaminants (Matheson model: 460/461 and Balston model 100-18-DX and 100-18-BX) prior to use in test atmosphere. Chamber atmosphere consisted of a dilution air stream and an octamethyltrisiloxane vapour/carrier stream. The dilution air stream was building-conditioned air (i.e. warmed and humidified) passed through activated carbon and HEPA filters. The carrier air stream was compressed air passed through a series of particulate filters prior to use in vapour generation.
- 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. Test article was metered from a reservoir into the J-tube using a pump. Compressed air flowed through the J-tube at a controlled rate of 34.8 l/minute. 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 particle size determination: no data
- Treatment of exhaust air: no data
- 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 22.1-25.8°C. Chamber relative humidity was maintained within the range of 31.7%-46.6%, Chamber airflow, temperature and percent relative humidity were monitored continuously and recorded at approximately thirty-minute intervals.

TEST ATMOSPHERE
- Brief description of analytical method used: Test atmosphere oxygen content was measured once during the exposure period. 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. Chamber atmosphere was analysed using a Varian 3400 gas chromatograph equipped with a flame ionization detector (GC/ID) to determine the actual chamber concentration of test article. The concentration of test article in the chamber atmosphere during exposure period was evaluated approximately every 30 minutes. A continuously purged sample line was used to transfer a sample of the chamber atmosphere to the GC/FID for analysis.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

plus one 20 minute chamber equilibration time

Concentrations:

Measured 2350 ppm (22.6 mg/l)
Nominal 2448 ppm (23.5 mg/l)

No. of animals per sex per dose:

5 male, 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Mortality and morbidity were observed twice daily during the week and once daily on weekends. Following the exposure, animals were evaluated once daily for clinical signs. Individual body weights were collected prior to exposure for randomization. Following randomization, body weights were recorded on day 1 (prior to exposure), day 8, and day 15 (prior to terminal sacrifice).

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Complete gross pathology was carried out, no tissues were saved.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22.6 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no mortalities.

Clinical signs:

other: There were no clinical signs.

Body weight:

All body weights and weight gains were considered normal for both sexes.

Gross pathology:

There were no macroscopic abnormalities.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LC50 value of >22.6 mg/l (analytical) was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

22.6 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:

21 Jan 2009 - 10 Feb 2009

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))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

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
- Age at study initiation: males 9 weeks, females 11 weeks
- Weight at study initiation: 232.8 - 322.3 g
- Housing: During acclimation in groups of 5 per sex in Makrolon type - 4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet.
- Water: Community tap water
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light):

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: The test item was applied evenly on the intact skin with a syringe and covered with a surgical gauze pad, held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water after the removal of the dressing and dapped off with disposable paper towels
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.44 ml

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male, 5 female.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs during the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.

- Necropsy of survivors performed: yes

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.

Clinical signs:

other: No clinical or local signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

An LD₅₀ value of >2000 mg/kg is reported in the acute oral key study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 2004a). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy.

The reported acute inhalation LC₅₀ value is >22.6 mg/l to vapour in the key study conducted according to an appropriate OECD test guideline and in compliance with GLP (Dow Corning Corporation, 2004b). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy. Furthermore, all body weight gains were considered normal for both sexes. A reliable supporting study is also available for acute inhalation toxicity in which the LC₅₀ value of >5.65 mg/l (analytical) is reported (TNO 2000) and was conducted according to the appropriate OECD test guideline, and in compliance with GLP. During the exposure to the aerosol breathing abnormalities were seen including a slightly increased breathing rate and laboured breathing which developed from slight to moderate. Shortly after exposure, piloerection and lethargy were seen in all animals. On the following days, these or other abnormalities were no longer seen and no mortality occurred. Body weight gain was considered within the normal limits for animals of this strain and age. At necropsy, treatment related abnormalities consisted of discoloured areas (in two animals) and petechia (in five animals) on the lobes of the lungs.

An LD₅₀ value of >2000 mg/kg is reported in the acute dermal key study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning 2009). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy.

Justification for classification or non-classification

Based on the available acute toxicity studies on the registered substance, no classification is proposed for acute toxicity according to Regulation (EC) No 1272/2008.