Registration Dossier

Administrative data

Description of key information

The key acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, concluded an LD50 value of >2000 mg/kg bw (NOTOX B.V., 2007).

The key acute inhalation toxicity study, conducted according to OECD Test Guideline 403 with acceptable restrictions and in compliance with GLP, concluded a 4-hour LC50 value of >5.8 mg/l as vapour (measured) (Dow Corning Corporation, 1994). The restriction of the study was that the limit concentration tested is below the recommended limit concentration according to the most recent guideline (20 mg/l). The acute inhalation toxicity data for the structutal analogue, hexamethyldisiloxane (HMDS), support the conclusion that no further testing for acute inhalation toxicity is necessary. In the study, an acute inhalation LC50 of 15,956 ppm (equivalent to 105.97 mg/L) with (95% confidence limits of 14,024-34,045) was determined for male and female rats.

In accordance with Column 2 of REACH Annex VIII, an acute toxicity study via the dermal route (required in Section 8.5.3 of REACH Annex VIII) does not need to be conducted if acute toxicity studies are available for the oral and one other appropriate route.

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:
17 January 2006 to 10 April 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
(temporary deviations from the minimum level of relative humidity occurred (27%, a minimum of 30% is recommended))
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: JMAFF guidelines (2000), including the most recent partial revisions at time of reporting
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 12 weeks
- Weight at study initiation: not exceeding ± 20% of the mean
- Fasting period before study: food withheld overnight (a maximum of 20 hours) prior to dosing until 3-4 hours after test substance administration
- Housing: in groups of three in labelled Macrolon cages (MIV type)
- Diet (e.g. ad libitum): standard diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 to 22.6
- Humidity (%): 27 to 63
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 January 2006 To: 2 February 2006
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.667 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (3 females in first and second set)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (dosing on day 1, observation until day 15)
- Frequency of observations and weighing: clinical signs monitored "at periodic intervals on the day of dosing", apparently 0, 2 and 4 hours after treatment, and then once daily until day 15. Body weights were recorded on days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
mortality
Remarks on result:
other: no mortality at 2000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
other: OECD Test Guideline 423
Remarks on result:
other: No mortalities in a 2-step test starting with 2000 mg/kg bw suggests an LD50 cut-off value of at least 5000 mg/kg bw, according to the OECD guideline
Mortality:
No mortality occurred over the course of the study.
Clinical signs:
Piloerection or hunched posture was seen in two animals on day 1.
Body weight:
Mean body weight gain considered normal. Slight body weight loss (2 g) between days 8 and 15 in one animal was not considered indicative of toxicity, based on the absence of any corroborative findings.
Gross pathology:
No macroscopic abnormalities found at post mortem.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined
Interpretation of results:
GHS criteria not met
Conclusions:
The key acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, concluded an LD50 value of >2000 mg/kg bw.
Executive summary:

The test substance was tested for acute oral toxicity to rats in study conducted according to OECD Test Guideline 423 and in compliance with GLP.

Three female Wistar rats were given a single oral gavage administration of 2000 mg/kg bw 1,1,3,3-tetramethyldisiloxane. The rats were then observed for fourteen days, after which they were sacrificed and subject to gross necropsy. This process was then repeated with a further three female rats. 

Over the course of the study, there were no deaths or overt signs of systemic toxicity, besides piloerection and hunched posture, each seen in one animal on day 1. No significant, treatment-related effect on body weight was reported, and no macroscopic abnormalities were detected at post mortem examination.

The acute oral LD50 in rats was determined to be greater than 2000 mg/kg bw.

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:
1994-6-27 to 1994-7-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The limit concentration according to the current OECD TG 403 is 20 mg/l (vapour). The limit concentration tested at this study is below the current limit value.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, NY, USA
- Age at study initiation: 49 days
- Weight at study initiation: 159-165 g (m); 107-119 g (f)
- Housing: individual stainless wire mesh cages
- Diet: standard diet ad libitum except during exposure
- Water: drinking water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25
- Humidity (%): 9% (during exposure - no details given for observation period)
- Air changes (per hr): 40L/min
- Photoperiod (hrs dark / hrs light): 12h/12 h

IN-LIFE DATES: From: 27 June 1994 To: 11 July 1994
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel/glass exposure chamber
- Exposure chamber volume: 160 L
- Method of holding animals in test chamber: caged
- Source and rate of air: compressed air system
- System of generating vapour: compressed air through glass vapourization collumn containing glass beads. Additional dilution air sweeps vapour into exposure chamber
- Method of particle size determination: conducted to ensure no aerosol (Andersen 8-stage cascade impactor)
- Temperature, humidity, pressure in air chamber: 25 deg C, 9% humidity

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatographic method (details in appendix not included with report)
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC
Duration of exposure:
4
Concentrations:
nominal 5 mg/l
measured 5.8 mg/l
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: body weight days 0, 7, 14; general observations twice daily for 14 days
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The recommended limit concentration according to the current guideline is 20 mg/l (vapour).
Mortality:
0/10 deaths
Clinical signs:
other: Rapid respiration and salivation.
Body weight:
All exposed animals gained weight.
Gross pathology:
No treatment-related abnormalities reported.

Table 1: Concentrations, mortality or evident toxicity

Sex

Analytical Conc. (mg/l)

Mortality (No./total)

Overt toxicity

Number with remarkable gross pathology

males

5.8

0/5

Rapid respiration and salivation. No treatment-related effects at 7 and 14 days.

0/5

females

5.8

0/5

Rapid respiration and salivation. No treatment-related effects 14 days.

0/5

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
The key acute inhalation toxicity study, conducted according to OECD Test Guideline 403 with acceptable restrictions and in compliance with GLP, concluded a 4-hour LC50 value of >5.8 mg/l as vapour (measured) (Dow Corning Corporation, 1994). The restriction of the study was that the limit concentration tested is below the recommended limit concentration according to the most recent guideline (20 mg/l).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 800 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, concluded an LD50 value of >2000 mg/kg bw (NOTOX B.V., 2007). Three female Wistar rats were given a single oral gavage administration of 2000 mg/kg bw 1,1,3,3-tetramethyldisiloxane. The rats were then observed for fourteen days, after which they were sacrificed and subject to gross necropsy. This process was then repeated with a further three female rats. Over the course of the study, there were no deaths or overt signs of systemic toxicity, besides piloerection and hunched posture, each seen in one animal on day 1. No significant, treatment-related effect on body weight was reported, and no macroscopic abnormalities were detected at post mortem examination.

 

The key acute inhalation toxicity study, conducted according to OECD Test Guideline 403 with acceptable restrictions and in compliance with GLP, concluded a 4-hour LC50 value of >5.8 mg/l as vapour (measured) (Dow Corning Corporation, 1994). The restriction of the study was that the limit concentration tested is below the recommended limit concentration according to the most recent guideline (20 mg/l). No toxic effects were reported when male and female rats were exposed for 4 hours to a measured atmosphere containing 5.8 mg/l (vapour) of the test material. No mortality was observed throughout the course of the study. The clinical signs included rapid respiration and salivation. All exposed animals gained weight. No treatment-related were abnormalities reported.

The available data for hexamethyldisiloxane (HMDS) have been included to the dataset to support read across for genetic toxicity and skin sensitisation.

Justification for classification or non-classification

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