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-tetravinylcyclotetrasiloxane

Endpoint summary

Description of key information

There are no skin sensitisation 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 skin sensitisation study was read-across from octamethylcyclotetrasiloxane D4 (CAS 556-7-2). In the key reliablity 1, guinea pig maximisation test (GMPT) conducted according to OECD TG 406 and GLP, D4 was not sensitising to the skin (Institut für Toxikologie der Bayer AG , 1985).

The second skin sensitisation study was read-across from the structural analogue decamethylcyclopentasiloxnae D5 (CAS 541-02-6). In a Local Lymph Node Assay (BSL Bioservice Scientific Labs, 2005) conducted using a protocol similar to OECD TG 429 and to GLP, D5 gave a negative result and is therefore not expected to be a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The first skin sensitisation study was read-across from octamethylcyclotetrasiloxane D4 (CAS 556-7-2). In this sensitisation study (GMPT) (Institut für Toxikologie der Bayer AG , 1985) albino guinea pigs were tested appropriately and in accordance with OECD TG 406, and to GLP. A preliminary test was conducted to determine irritancy and the concentrations to be used in the main study. Paraffin oil was used as the vehicle. In the main study 20 guinea pigs were tested with 1% D4 in paraffin oil in the first induction, and 100% D4 in the second induction. 100% and 10% (in paraffin oil) were used in the challenge phase under occlusive conditions. Ten negative control animals received the same treatment, but without D4. Evaluation of skin reactions were made at 48, 72 and 96 hours after challenge. Skin reactions in the test and control groups were all scored as zero, and therefore under the conditions of this study, D4 was not a skin sensitiser.

The second skin sensitisation study was read-across from the structural analogue decamethylcyclopentasiloxane D5 (CAS 541-02-6). The study for skin sensitisation (BSL Bioservice Scientific Labs, 2005) was conducted using a protocol similar to OECD TG 429. Each mouse (5 CBA mice treated in total) was tested by topical application of 25 µl of the selected solution (10, 50 and 100% D5) to the entire dorsal surface of each ear. Topical applications were performed once daily over three consecutive days. Five days after the first topical application treatment, all mice were dosed with 20 µCi 3H-methyl thymidine by intravenous injection (tail vein) of 250 µl of 3H-methyl thymidine, diluted to a working concentration of 80 µCi/ml. Before sacrificing the animals the thickness of the ears of all animals was determined again. Approximately 5 hours after 3H-methyl thymidine injection all mice were sacrificed. The draining auricular Iymph nodes were excised, pooled for each animal (2 lymph nodes per animal, if technically possible) and collected in PBS. A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through polyamid gauze (200 mesh size). After washing the gauze with PBS the cell suspension was pelleted in a centrifuge. The supernatant was discarded and the pellets were resuspended with PBS. This washing procedure was repeated. After the final wash each pellet was resuspended in approx. 1 mL 5% TCA at approx. 4 °C overnight for precipitation of macromolecules. Each precipitate was once washed again, resuspended in 10 mL scintillation fluid and transferred into scintillation vials. The 3H-methyl thymidine - incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5% TCA). Determination of radioactivity was performed individually for each animal. An EC3 value (derived by linear interpolation) could not be calculated as all concentrations tested showed a stimulation index below 3. Therefore D5 was negative for skin sensitisation under the conditions of this study.

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 skin sensitisation. 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, octamethylcyclotetrasiloxane D4 (CAS 556-67-2) , 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 35°C and pH 5 (relevant for dermal exposure), the hydrolysis half-life is expected to be between the values for pH 4 (0.9 h) and pH 7 (25 h). 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 decamethylcyclopentasiloxane D5 (CAS 541-02-6) 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. At 35°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life is expected to be between the values for pH 4 (4.3h) and pH 7 (590 h). 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. The product of hydrolysis is dimethylsilanediol.

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, Vi5D5 and Vi4D4. 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 at pH 5		Component 1 Vi5 -D5 > 1.5 min < 600 h at37.5 ºC  Component 2 Vi5 -D4 > 15 sec < 23 h at37.5 ºC		0.9 h < t < 25h at 35ºC		4.3 h < t < 590 h at 35ºC
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		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		17 µg/L at 23°C

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

The first skin sensitisation study was read-across from octamethylcyclotetrasiloxane D4 (CAS 556-7-2). The study was conducted according to an appropriate OECD Test Guideline and in compliance with GLP. In this sensitisation study (GMPT) (Institut für Toxikologie der Bayer AG , 1985) albino guinea pigs were tested appropriately and in accordance with OECD test guideline 406, and to GLP. A preliminary test was conducted to determine irritancy and the concentrations to be used in the main study. Paraffin oil was used as the vehicle. In the main study 20 guinea pigs were tested with 1% D4 in paraffin oil in the first induction, and 100% D4 in the second induction. 100% and 10% (in paraffin oil) were used in the challenge phase under occlusive conditions. Ten negative control animals received the same treatment, but without D4. Evaluation of skin reactions were made at 48, 72 and 96 hours after challenge. Skin reactions in the test and control groups were all scored as zero, and therefore under the conditions of this study, D4 was not a skin sensitiser.

The second skin sensitisation study was read-across from the structural analogue decamethylcyclopentasiloxane D5 (CAS 541-02-6). The study for skin sensitisation (BSL Bioservice Scientific Labs, 2005) was conducted using a protocol similar to OECD Test Guideline 429 and in compliance with GLP. Each mouse (5 CBA mice treated in total) was tested by topical application of 25 µl of the selected solution (10, 50 and 100% D5) to the entire dorsal surface of each ear. Topical applications were performed once daily over three consecutive days. Five days after the first topical application treatment, all mice were dosed with 20 µCi 3H-methyl thymidine by intravenous injection (tail vein) of 250 µl of 3H-methyl thymidine, diluted to a working concentration of 80 µCi/ml. Before sacrificing the animals the thickness of the ears of all animals was determined again. Approximately 5 hours after 3H-methyl thymidine injection all mice were sacrificed. The draining "auricular Iymph nodes" were excised, pooled for each animal (2 lymph nodes per animal, if technically possible) and collected in PBS. A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through polyamid ganze (200 mesh size). After washing the gauze with PBS the cell suspension was pelleted in a centrifuge. The supernatant was discarded and the pellets were resuspended with PBS. This washing procedure was repeated. After the final wash each pellet was resuspended in approx. 1 mL 5% TCA at approx. 4 °C overnight for precipitation of macromolecules. Each precipitate was once washed again, resuspended in 10 mL scintillation fluid and transfered into scintillation vials. The 3H-methyl thymidine - incorporation was measnred in a ß-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5% TCA). Determination of radioactivity was performed individually for each animal. An EC3 value (derived by linear interpolation) could not be calculated as all concentrations tested showed a stimulation index below 3. Therefore D5 was negative for skin sensitisation under the conditions of this study.

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 skin sensitisation profiles. 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. However, considering that the hydrolysis half-lives for these three substances are very slow it is likely that the parent substance would not undergo hydrolysis and the test organism would be exposed to the parent only.  

There are no data available for the hydrolysis products, dimethylsilanediol and methylvinylsilanediol.

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 skin sensitisation study with the source substance, D4, was reported to be >99%.

The test substances in the skin sensitisation study with the second source substance D5, have a purity of 87% decamethylcyclopentasiloxane and 13% 443892-05-5 Silicone Gel.

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

Not relevant.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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 skin sensitisation based on Regulation (EC) No. 1272/2008.