Registration Dossier

Administrative data

Description of key information

The key study for acute oral toxicity reports an LD50 value of >2000 mg/kg bw which was determined in a reliable study with the registered substance, carried out in accordance with OECD TG 425 and in compliance with GLP (RCC 2008).

The acute inhalation study is read across from octamethyltrisiloxane (L3, CAS 107-51-7). The animals were exposed to vapour and 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 (Dow Corning 2004). In addition, a study was conducted according to OECD 403 and in compliance with GLP for the read-across substance 1,1,3,3-tetramethyldisiloxane (H2 -L2, CAS 3277-26-7). The animals were exposure to vapour and an LC50 value >5.8 mg/l (measured) was determined (Dow Corning Corporation, 1994).

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the dermal route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and inhalation routes are available.

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:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Switzerland
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 176.5-199.5
- Fasting period before study:
- Housing: Individually in Makrolon type-3 cages with wire mesh tops and standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: yes, but time period not specified in report

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:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml

- Justification for choice of vehicle: The vehicle was chosen after a non-solubility trial which was performed before the study initiation date. This formulation trial is excluded from the statement of compliance. The test item prepared in corn oil was well-soluble.

- Lot/batch no. (if required): 18787208


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

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: The animals were examined daily during the acclimation period and mortality; viability and clinical signs were recorded. All animals were examined for mortality/viability and clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once (twice for mortality/viability) daily during test days 2-15. Body weights were recorded on test day 1 (prior to removal of food), on test days 1 (prior to administration) 8 and 15. All animals were necropsied and examined macroscopically.

- Necropsy of survivors performed: yes

Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Mortality:
All animals survived until the end of the study period.
Clinical signs:
Slightly to moderately ruffled fur was noted in all animals from the 1- or 5- hour reading up to test day 2 or 3, with persisting in one animal through test day 7. Slight to marked sedation was recorded in all animals from the 2-, 3- or 5-hour observation up to 5 hours post-dose or test days 2 or 3. Two animals showed slightly poor coordination on test day 2 only, while two other animals showed slight to markedly or slightly to moderately poor coordination from 5 hours post-dose until test day 2. Hunched posture was observed in four animals at the 1-hour reading and persisted through the 5-hour evaluation in one animal and through test day 2 in three animals. Ventral recumbency was noted in one animal on test day 2.
Body weight:
The body weight of animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded 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 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:
guideline study
Qualifier:
according to
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. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals 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 a 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 concertation 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.
Key result
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:
22 600 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for acute oral toxicity reported an LD50 value of >2000 mg/kg bw in rat, in a reliable and GLP compliant study (RCC 2008). There were no mortalities during the study period. Slightly to moderately ruffled fur was noted in all animals from the 1- or 5- hour reading up to test day 2 or 3, persisting in one animal through test day 7. Slight to marked sedation was recorded in all animals from the 2-, 3- or 5-hour observation up to 5 hours post-dose or test days 2 or 3. Two animals showed slightly poor coordination on test day 2 only, while two other animals showed slight to markedly or slightly to moderately poor coordination from 5 hours post-dose until test day 2. Hunched posture was observed in four animals at the 1-hour reading and persisted through the 5-hour evaluation in one animal and through test day 2 in three animals. Ventral recumbency was noted in one animal on test day 2. The body weight of animals was within normal range. No macroscopic findings were recorded at necropsy.

The key study for acute inhalation was read across from octamethyltrisiloxane (L3, CAS 107-51-7). The study was conducted according to an appropriate OECD/EU test guideline, and in compliance with GLP. The reported LC50 value is >22.6 mg/l (Dow Corning 2004). There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy. Furthermore, all body weight gains were considered normal for both sexes.

Read across was also included for acute inhalation from the related substance 1,1,3,3-tetramethyldisiloxane (H2 -L2, CAS 3277-26-7).

The study was conducted according to an appropriate OECD/EU test guideline, and in compliance with GLP. A well reported study, conducted according to generally accepted scientific standards and in accordance with GLP, found no toxicity when male and female rats were exposed for 4 h to a measured atmosphere containing 5.8 mg/l (vapour) of the test material. The LC50 would exceed this value. There were no treatment-related abnormalities reported. Clinical signs of rapid respiration and salivation were recorded. There were no mortalities (Dow Corning Corporation, 1994).


Justification for classification or non-classification

Based on the available information, no classification is necessary for acute toxicity in accordance with Regulation (EC) No 1272/2008.