Registration Dossier

Administrative data

Description of key information

The key study for acute oral toxicity was read across from the structurally analogous substance octamethylcyclotetrasiloxane (CAS 556-67-2). An LD50 value of >5 ml/kg (equivalent to >4800 mg/kg bw) was determined in a reliable study conducted according to a test protocol that is comparable to the appropriate OECD test guideline, but not compliant with GLP (Löser, 1979). The acute inhalation study reports a vapour LC50 value of >1.32 mg/l (analytical) which was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 800 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
1 320 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for acute oral toxicity read across from the structurally analogous substance octamethylcyclotetrasiloxane (CAS 556-67-2). The LD50 value of >5ml/kg (equivalent to >4800 mg/kg bw) in rat, is reported in a reliable but non-GLP compliant study (Löser, 1979). There were no mortalities or clinical signs during the study period. Gross pathology was not reported.

The key study for acute inhalation was conducted according to an appropriate OECD/EU test guideline. The reported LC50 value is >1.32 mg/l vapour, which was the maximum achievable concentration (DCC 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.

Read-across justification

2,4,6,8-Tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4) is one of a number of cyclic siloxanes for which acute toxicity data are available.The substances all have high log Kow and low water solubility. Acute toxicity studies by the oral, dermal and inhalation routes are available for a number of these substances. For the registration substance itself, the only available acute toxicity study is for the inhalation route (Dow Corning Corporation, 1988), in which there were no mortalities up to the limit concentration that could be tested.

The results of all available studies, summarised in the table below, are in agreement and show that there is no evidence from any of the available studies that the substances in this group have any potential for acute toxicity (in terms of either lethality or adverse clinical effects) by any route up to and exceeding the maximum dose levels tested according to current OECD guidelines.Furthermore, data for related alkoxysilane substances (which share common hydrolysis products with the cyclic siloxanes) show that the presence of a vinyl group in place of a saturated alkyl group does not cause any enhanced toxicity effect. Full details of the available data for the alkyl alkoxysilanes is given in a supporting report attached in Section 13 (PFA, 2013t).

It is therefore valid to read-across the lack of acute toxicity between the members of the group where there are data gaps.

 

Acute toxicity data for cyclic siloxanes

 

CAS Number

Name

Synonym

log Kow

Acute oral toxicity LD50mg/kg bw)

Acute dermal toxicity LD50mg/kg bw)

Acute inhalation toxicity LC50(mg/l)

556-67-2

Octamethylcyclotetrasiloxane

D4

6.5

>4800 (Löser, 1979)

>2400 (Ramm, 1985)

36 mg/l (Dow Corning Corporation, 1994)

2554-06-5

2,4,6,8-Tetramethyl-2,4,6,8-tetramethylcyclotetrasiloxane

Vi4-D4

6.5

-

-

>1.32 mg/l (Dow Corning Corporation, 1988)

2370-88-9

2,4,6,8-tetramethylcyclotetrasiloxane

HD4

5.5

>2000

(Arcelin, 2010a)

-

-

541-02-6

Decamethylcyclopentasiloxane

D5

8.0

>5000 (Toxikon, 1990a)

>2000 (WIL, 1977)

8.7 mg/l (RCC, 1994)

6166-86-5

2,4,6,8,10-pentamethylcyclopentasiloxane

HD5

6.3

>2000 (Arcelin, 2010b)

-

-

540-97-6

Dodecamethylcyclohexasiloxane

D6

8.9

>2000 (Notox, 1999a)

>2000 (Notox, 1999b)

-

The most recent and reliable available studies were selected as key.

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 decamethylcyclopentasiloxane D5 (CAS 541-02-6), data for Vi3-D3 are read-across from hexamethyltrisiloxane D3 (CAS 541-05-9).

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

For D5, the key acute oral toxicity study (Momentive, 1990), which was comparable to the now deleted OECD 401, and conducted according to 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), which was comparable to OECD 403, and conducted according to 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 (Procter&Gamble, 1977), which was pre-GLP, but comparable to OECD 402, 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) [IMPURITY 2]

No acute inhalation tests are available for D3 or dimethylsilanediol. 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 test data, 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane is not classified for acute toxicity according to Regulation (EC) No 1272/2008.