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Description of key information

There are no acute oral toxicity studies available for Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-

pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane (EC 911-381-6). Therefore, the Annex requirements are fulfilled with data on structurally analogous substances.

The first acute oral study was read-across from octamethylcyclotetrasiloxane (D4) (CAS 556-7-2). In this single-dose only acute oral study (Bayer AG, 1979) in male rats, the LD50 was greater than 4800 mg/kg bw. There were no deaths or clinical signs of toxicity at this dose.

The second acute oral study was read-across from decamethylcyclopentasiloxane (D5) (CAS 541 -02 -6). In this study (Toxikon Corporation, 1990), which was comparable to the now deleted OECD 401, and to GLP, the LD50 value for male and female rats was >5000 mg/kg bw.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The first acute oral study was read-across from octamethylcyclotetrasiloxane (D4) (CAS 556-67-2). In the study (Bayer AG, 1979), Wistar rats (10 male) were administered oral by gavage with a single dose of 5.0 ml/kg bw (4800 mg/kg bw) of D4. The animals were then observed for 14 days for mortality and signs of toxicity. At the end of the observation period the animals were sacrificed and a histopathological examination conducted and organ weights recorded (organs not specified). There were no adverse findings reported. Other results from supporting studies in rats are in agreement with the conclusion that D4 is not harmful via the oral route. A Reliability 2 study in mice (Pasquet and Mauret, 1971) gave an LD50 of 1700 mg/kg. However, this value is not selected for read-across since rat is the preferred species for classification and labelling purposes. 

The second acute oral study was read-across from decamethylcyclopentasiloxane (D5) (CAS 541 -02 -6). The study (Toxikon Corporation, 1990a) was conducted according to the now deleted OECD test guideline 401. Sprague-Dawley rats (5 animals/sex) were given D5 as an oral gavage dose of 5000 mg/kg bw. The animals were then observed for mortality and clinical signs of toxicity for 14 days. A necropsy examination was conducted on each animal following the 14 day observation period. There were no deaths, no signs of toxicity, and growth and necropsy findings were normal. The LD50 for male and female animals was therefore >5000 mg/kg bw.

Read-across justification

There are no available measured data for Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane for acute toxicity. Therefore, the Annex requirements are fulfilled with data on structurally analogous substances. This document describes the analogue approach for fulfilling this endpoint by read-across from two source substances, octamethylcyclotetrasiloxane (D4) (CAS 556-67-2) and decamethylcyclopentasiloxane (D5) (CAS 541-02-6), according to the Read-across Assessment Framework (RAAF) .

Read-across is proposed in accordance with RAAF Scenario 2: “This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case.”

The read-across justification is presented (Table 5.6.4) according to RAAF scenario 2 assessment elements (AE) as outlined in Table B1 of the RAAF1:

Table 1: RAAF scenario 2 assessment elements (AE) as given in Appendix B (Table B1) of the RAAF1

AE A.1

Characterisation of source substance

AE A.2

Link of structural similarity and differences with the proposed Prediction

AE A.3

Reliability and adequacy of the source study

AE 2.1

Compounds the test organism is exposed to

AE 2.2

Common underlying mechanism, qualitative aspects

AE 2.3

Common underlying mechanism, quantitative aspects

AE 2.4

Exposure to other compounds than to those linked to the prediction

AE 2.5

Occurrence of other effects than covered by the hypothesis and Justification

AE A.4

Bias that influences the prediction

1.       AE A.1 Identity and characterisation of the source substance

The first source substance, D4, is a cyclic siloxane made up of four silicon atoms linked by oxygen atoms, where each silicon atom is fully methyl substituted. Its measured hydrolysis half lives are: 1.8 h at pH 4, 69 - 144 h at pH 7, 0.9 - 1 h at pH 9, and 25°C (OECD 111). At pH 2 (the known pH of the stomach), the hydrolysis rate is approximately 5 seconds. At physiological temperature 35ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half- life is calculated as 0.006 h (approximately 22 seconds). The product of hydrolysis is dimethylsilanediol.

The source substance has log Kow of 6.49 at 25.1°C (OECD 123), water solubility of 0.056 mg/l at 23°C and vapour pressure of 132 Pa at 25°C.

The second source substance, D5, is a cyclic siloxane made up of five silicon atoms linked by oxygen atoms. In D5, each silicon atom is fully methyl substituted. Its measured hydrolysis half-lives at 25°C are: 9.3 h at pH 4, 351 h at pH 5.5, 1590 h (66 d) at pH 7, 214 h at pH 8 and 24.8 - 31.6 h at pH 9. The calculated half-life of D5 at pH 2 and 35°C (relevant for conditions in the stomach following oral exposure) is 0.043 hours (approximately 3 minutes).  The product of hydrolysis is dimethylsilanediol.The source substance has log Kow of 8.02 at 25.3 °C, water solubility of 17 µg/L at 23°C and vapour pressure of 33.2 Pa at 25°C.

2.       AE A.2 Link of structural similarities and differences with the proposed prediction

The registration substance, Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane, has two components, Vi5-D5 and Vi4-D4. Component 2, Vi4-D4, and the first read-across substance, D4,  are both cyclic siloxanes made up of four silicon atoms linked by oxygen atoms. In D4, each silicon atom is fully methyl substituted, whereas in Vi4-D4 each silicon atom is substituted with one methyl and one vinyl group. Vi4-D4 and D4 have slow hydrolysis rates (63 h at pH 7 and 20-25°C, predicted and 69-144 h at pH 7 and 25°C, respectively) and similar physico-chemical properties: high molecular weight (MW 344.7 and 296.6 respectively), low water solubility (0.0073 – 0.0088 mg/l and 0.056 mg/l, respectively), high log Kow (both 6.5) and high log Koc (both close to 4). D4 and Vi4-D4 are structural analogues with very similar properties.

Similarly, component 1, Vi5-D5, and the second read-across substance, D5, are cyclic siloxanes made up of five silicon atoms linked by oxygen atoms. In D5, each silicon atom is fully methyl substituted, whereas in Vi5-D5 each silicon atom is substituted with one methyl and one vinyl group. Vi5-D5 and D5 have slow hydrolysis rates (1600 h at pH 7 and 20-25°C, predicted and 1590 h at pH 7 and 25°C respectively) and similar physico-chemical properties: high molecular weight (MW 431 and 370.8 respectively), low water solubility (9.1E-06 mg/l and 0.017 mg/l respectively) high log Kow (9.0 and 8.0 respectively) and high log Koc (6 and 5.2 respectively). D5 and Vi5-D5 are structural analogues with very similar properties.  

Table 2: Physico-chemical properties

Property

Target substance

Source substance

Source substance

Substance name

Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane

octamethylcyclotetrasiloxane (D4)

decamethylcyclopentasiloxane (D5)

CAS number

Not applicable

556-67-2

541-02-6

Hydrolysis half-life

component 1 Vi5D5: 0.025 h (approximately 1.5 minutes)

component 2 Vi4D4: 0.004h (approximately 15 seconds) at 35ºC and pH 2

0.006 h (approximately 22 seconds) at 35ºC and pH 2

0.043 hours (approximately 3 minutes) at 35ºC and pH 2

Silanol hydrolysis product

Methylvinylsilanediol

dimethylsilanediol

dimethylsilanediol

Non-Si hydrolysis product

none

none

none

LogKow value

component 1 Vi5D5: 9 (predicted), component 2 Vi4D4: 6.47 (measured)

6.49 at 25.1°C (OECD 123)

8.02 at 25.3 °C

Vapour pressure

component 1 Vi5D5: 0.6 Pa at 25°C (predicted), component 2 Vi4D4: 93.5 Pa at 25°C (measured)

132 Pa at 25°C

33.2 Pa at 25°C

Water solubility

component 1 Vi5D5: 9.1E-06 mg/l (predicted) , component 2 Vi4D4: 0.0073-0.0088 mg/l at 23°C (measured)

0.056 mg/l at 23°C

0.017 mg/l at 23°C

3.       AE A.3 Reliability and adequacy of the source study

The first acute oral study for 2,2,4,4,6,6,8,8-octamethyl-1,3,5,7,2,4,6,8-tetroxatetrasilocane (CAS 556-67-2) was conducted according to an appropriate OECD Test Guideline and in compliance with GLP. In the study (Bayer AG, 1979), Wistar rats (10 male) were administered oral by gavage with a single dose of 5.0 ml/kg bw (4800 mg/kg bw) of D4. The animals were then observed for 14 days for mortality and signs of toxicity. At the end of the observation period the animals were sacrificed and a histopathological examination conducted and organ weights recorded (organs not specified). There were no adverse findings reported. Other results from supporting studies in rats are in agreement with the conclusion that D4 is not harmful via the oral route.

The second acute oral study for 2,2,4,4,6,6,8,8,10,10-decamethyl-1,3,5,7,9,2,4,6,8,10-pentoxapentasilecane (CAS 541 -02 -6), was conducted according to an appropriate OECD Test Guideline and in compliance with GLP. The study (Toxikon Corporation, 1990a) was conducted according to the now deleted OECD test guideline 401. Sprague-Dawley rats (5 animals/sex) were given D5 as an oral gavage dose of 5000 mg/kg bw. The animals were then observed for mortality and clinical signs of toxicity for 14 days. A necropsy examination was conducted on each animal following the 14 day observation period. There were no deaths, no signs of toxicity, and growth and necropsy findings were normal. The LD50 for male and female animals was therefore >5000 mg/kg bw.

4.       AE A.4 Bias that influences the prediction

Data on the source substances D4 and D5 were read-across to the registered (target) substance Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane. The source substances and the target substance have similar chemical structure and physico-chemical properties. All three substances hydrolyse at similar rate, and produce similar silicon-containing hydrolysis products, dimethylsilanediol and methylvinylsilanediol. None of them gives a non-silanol hydrolysis product. Therefore, their toxicological properties are expected to be similar, with similar acute toxicity. No other data for relevant substances were available. These substances are the closest structural analogues to the target substance.

5.       AE A.2.1 Compounds the test organism is exposed to

The source substances as well as the target substance hydrolyse at similar rate in contact with water under conditions relevant for oral exposure. Therefore, the test organism could possibly be exposed to the parent substance and their hydrolysis products, dimethylsilanediol or methylvinylsilanediol.

An acute oral toxicity study is available for the hydrolysis product, dimethylsilanediol (WIL 2007). Initially, the test article was administered once orally via gavage at the limit test level of 2000 mg/kg to a single fasted female albino rat. No mortality was observed, and 4 additional animals were dosed at 2000 mg/kg. Mortality, clinical observations and body weight changes were evaluated over a 14-day observation period. All treated animals were subjected to a gross necropsy. One animal was found dead on study day 2. Clinical findings limited to this animal included impaired equilibrium, partial closure of the right and left eyes, hypoactivity, decreased respiration, soft feces, pale body and extremities and body cool to touch. Clinical findings for all animals included wet yellow material on the urogenital, anogential areas and/or ventral trunk. There were no remarkable body weight changes. There were no remarkable gross necropsy findings. Based on the results of this study, the estimated LD50 of dimethylsilanediol is greater than 2000 mg/kg when administered once orally via gavage to fasted female albino rats.

There are no data available for the hydrolysis product methylvinylsilanediol. However, the presence of a vinyl group in place of a saturated alkyl group is not expected to cause any enhanced toxicity effect (PFA, 2013t).

6.       AE A.2.2 and A.2.3 Common underlying mechanism, qualitative and quantitative aspects

No toxicity data are available for the target substance Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane, therefore data are read-across from the structurally analogous substances D4 and D5. These three substances hydrolyse at similar rate to a silanol (2 moles). There are no non-silanol hydrolysis products relevant for this endpoint. Moreover, they have similar physico-chemical properties. Thus, all three substances are expected to have similar toxicity profiles.

7.       AE 2.4 Exposure to other compounds than to those linked to the prediction

The registration substance, Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane, has two components, Vi5D5 and Vi4D4, with purity greater than 80% for both components.

Neither the target substance nor the source substances have impurities of toxicological concern.

Purity of test substance in the study with the source substance, D4, was not reported. However, the Substance Identity Profile for the REACH Registration of this substance indicates that it has a purity of >98% and no impurities are present at >1%.

The test substance in the study with the second source substance D5, has a purity of >95%.

8.       AE 2.5 Occurrence of Other Effects than Covered by the Hypothesis and Justification

Not relevant.

References:

WIL (2007): Acute Oral Toxicity Study of Dimethylsilanediol (DMSD)) in Albino Rats (Up-and Down Procedure), WIL Research Laboratories, Unpublished study report WIL-401007

Analogue report: Mammalian toxicity of linear and branched siloxanes, PFA, 2013t.

Justification for classification or non-classification

Based on the available information for

Reaction Mass of 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane and 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl cyclotetrasiloxane, no classification is required for acute oral toxicity based on Regulation (EC) No. 1272/2008.

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