Registration Dossier

Administrative data

Description of key information

There are no acute oral toxicity data for the registered substance, 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane. Therefore, data for the structural analogue, octamethyltetroxatetrasiloxane (D4, CAS 556-67-2) have been read across for these endpoints. Furthermore, read across data from decamethylcyclopentasiloxane (D5, CAS 541-02-6) and hexamethylcyclotrisiloxane (D3, CAS 541-05-9) for the impurities 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane Vi5-D5 (CAS 17704-22-2; Impurity 1) and 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane Vi3-D3 (CAS 3901-77-7; Impurity 2) have been included as supporting information where available.

In the key study for acute oral toxicity with D4, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP, an LD50 value of >5 ml/kg (equivalent to >4800 mg/kg bw) was concluded (Bayer AG, 1979).

In the key acute inhalation toxicity study with Vi4-D4, conducted according to OECD 403 and in compliance with GLP, the reported LC50 (vapour) value is >1.32 mg/l (analytical) (Dow Corning Corporation, 1988).

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
A single oral adminitration of 5ml/kg of test substance to 10 male rats. Observation period 14 days.
GLP compliance:
no
Test type:
other: LD50
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Wikelmann

- Weight at study initiation: 160-180g

- Housing: 5 animals per cage



Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No detail available.

Doses:
5.0 ml/kg bw
No. of animals per sex per dose:
10M
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: no detail available

- Necropsy of survivors performed: not specified

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No detail available.
Statistics:
No statistical analysis reported.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 800 mg/kg bw
Based on:
test mat.
Remarks on result:
other: > 5.0 ml/kg bw (> 4800 mg/kg bw)
Mortality:
No mortality.
Clinical signs:
No clinical signs.
Body weight:
No data available.
Gross pathology:
None reported.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral LD50 value of >5ml/kg (ca. 4800 mg/kg) was determined in a reliable study conducted according to an appropriate test protocol. Not conducted according to GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 800 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:
20 July 1987 - 03 August 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 175-250 g
- Housing: Standard stainless steel, wire mesh bottomed cages of conventional design.
- Diet: ad libitum, except during exposure
- Acclimation period: Seven days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 30-50
- 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 litre stainless steel and glass exposure chamber.
- Method of holding animals in test chamber:
- System of generating particulates/aerosols: Test material was introduced into the test chamber through a specifically designed glass J-tube with a low flow FMI Lab pump. Laboratory air filtered and dried with a Matheson #462 cartridge filter and Drierite cartridge passed through the J-tube. The air/vapour mixture entered the top of the chamber where it was diluted with room air to its maximum attainable concentration. Heating tape was used to heat the air which passed through the J-tube, and glass beads were used to further vapourise the test material.
- Method of particle size determination: Not reported
- Treatment of exhaust air: The exhaust air was filtered (hepa and carbon), cleaned with a water cyclone, then exhausted from the roof of the building.
- Temperature, humidity, pressure in air chamber: The chamber air was filtered (hepa and carbon) and temperature and humidity controlled. Chamber airflows were recorded hourly during the exposure period. Chamber temperature and relative humidity were monitored with Cole-Parmer Model No. 3310-40 (ceritfied) temperature and humidity gauges. Chamber temperature ranged from 23-24C. Percent relative humidity fell between 40% and 51% and chamber airflows were recorded as 107 to 114 L.P.M (corresponding to 14-15 air changes per hour).

TEST ATMOSPHERE
- Brief description of analytical method used: Not reported
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Not reported
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Not reported

Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
Analytical concentration for test group 1.32 mg/l, control group was exposed to filtered air. (A concentration of 5 mg/l was attempted but unsuccesful due to the low vapour pressure of the test material.
No. of animals per sex per dose:
5 males, 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Prior to exposure, animals were weighed and those within the acceptable weight range were randomized using a computer program. Individual observation records were maintained for each animal. Animals were observed once a day during weekdays. Individual animal body weights were taken prior to exposure and on days 7 and 14 after exposure.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The trachea was exposed and clamped such that the lungs could be removed and observed in an inflated state. Special attention was paid to the respiratory tract.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.32 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
There was no mortality observed in test or control group.
Clinical signs:
other: No apparent abnormalities were observed in either the control or test groups during the exposure or post-exposure periods.
Body weight:
There were no significant body weight differences exhibited by any test animals when compared to control animals.
Gross pathology:
No remarkable findings reported.
Other findings:
None reported.

On the basis of these results, it is concluded that the test material most likely does not pose an acute vapour inhalation hazard at the concentration attained.

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 was > 1.32mg/l which was the maximum achievable concentration.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 320 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no acute oral toxicity data for the registered substance, 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane. Therefore, data for the structural analogue, octamethyltetroxatetrasiloxane (D4, CAS 556-67-2) have been read across for these endpoints.

In the key study for acute oral toxicity with D4, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP, an LD50 value of >5 ml/kg (equivalent to >4800 mg/kg bw) was concluded (Bayer AG, 1979).

There were no mortalities or clinical signs during the study period. Gross pathology was not reported.

In the key acute inhalation toxicity study with Vi4-D4, conducted according to OECD 403 and in compliance with GLP, the reported LC50 (vapour) value is >1.32 mg/l (analytical) (Dow Corning Corporation, 1988).

There were no mortalities, no clinical signs or macroscopic abnormalities reported at necropsy. Furthermore, all body weight gains were considered normal for both sexes.

IMPURITY PROFILE

The registration substance has an average purity of >80% Vi4-D4, with <15% 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane Vi5-D5 (CAS 17704-22-2; Impurity 1) and <10% 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane Vi3-D3 (CAS 3901-77-7; Impurity 2) present as impurities. After due consideration of the properties, the presence of these impurities is not expected to affect the overall hazard profile of the substance. Read-across studies are in place as supporting studies, to consider the properties of the impurities. Data for Vi5-D5 are read-across from D5 (CAS 541-02-6), data for Vi3-D3 are read-across from D3 (CAS 541-05-9).

Read across from D5 (CAS 541-02-6) [SOURCE SUBSTANCE FOR IMPURITY 1]

For D5, the key acute oral toxicity study (Toxicon Corporation, 1990a), conducted according to a guideline comparable to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50value for male and female rats of >5000 mg/kg bw. There were no mortalities, clinical signs of toxicity or adverse findings at necropsy.

For D5, the key acute inhalation toxicity study (Dow Corning Corporation, 1994), conducted according to a guideline comparable to OECD Test Guideline 403 and in compliance with GLP, reports an LC50value of 8.67 mg/l. During exposure there was a concentration-dependent increase in restlessness observed at all exposure levels, an effect which was more pronounced in females than males. Following exposure stiff gait, hunched posture, ruffled fur, restlessness and tachypnea were observed in most or all rats from both sexes which survived the exposure, starting immediately after the exposure and lasting until study day 13. No significant findings were noted at necropsy in the lungs of animals surviving the treatment period. A treatment related effect seen in the animals that died was reddish or dark red colouration of the lungs and partially collapsed lungs. 

For D5, the key acute dermal toxicity study (WIL Research, 1977), conducted according to a protocol comparable to OECD Test Guideline 402, but pre-GLP, reports an LD50value of >2000 mg/kg bw. There were no mortalities, clinical signs of toxicity, adverse necropsy findings or signs of local irritation.

Read across from D3 (CAS 541-05-9) [SOURCE SUBSTANCE FOR IMPURITY 2]

There are no acute toxicity data available for D3.

However, a repeated dose toxicity study via the inhalation route (see Section 7.5.3) tested D3 at exposure levels up to the maximum attainable vapour concentration for this substance, for duration of 6 hours per day (Dow Corning Corporation, 2001). There was no mortality or evidence of specific target organ toxicity in this study. It can therefore be concluded that D3 would not be acutely toxic by the inhalation route up to the maximum attainable vapour concentration.

No other data are available to provide a read across entry for impurity 2 (<10%2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane Vi3-D3, CAS 3901-77-7). However, a concentration of <10% of Vi3-D3 in the product is unlikely to influence acute toxicity and there is no evidence from the available data on other cyclic siloxanes that potential for acute toxicity exists.


Justification for classification or non-classification

Based on the available read-across data, 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane is not classified for acute toxicity according to Regulation (EC) No 1272/2008.