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 and eye irritation/ 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 irritation study was read-across from octamethylcyclotetrasiloxane (CAS 556-7-2). In the study (Laboratoires de Recherches de la Societe des Usines, 1971), D4 was not irritating to rabbit skin. The study was conducted according to a protocol similar to OECD TG 404 but not in compliance with GLP.

The second skin irritation study was read-across from the structural analogue decamethylcyclopentasiloxane (CAS 541-02-6). In this skin irritation study (Toxikon Corporation, 1990b and c, respectively), which was conducted using protocols comparable with OECD TG 404, and in compliance with GLP, it was concluded that D5 was not irritating to the skin of rabbits.

The first eye irritation study was read-across from 556-7-2. In the key eye irritation study (Dow Corning Corporation, 1997) D4 was not irritating to the eyes of rabbits. The study was conducted according to an appropriate OECD TG 405 and in compliance with GLP.

The second eye irritation study was read-across from the structural analogue decamethylcyclopentasiloxane (CAS 541-02-6). In this eye irritation study (Toxikon Corporation, 1990b and c, respectively), which was conducted using protocols comparable with OECD TG 405, and in compliance with GLP, it was concluded that D5 was not irritating to the eyes of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The first skin irritation study was read-across from octamethylcyclotetrasiloxane, D4 (CAS 556-7-2). In this study (Laboratoires de Recherches de la Societe des Usines, 1971) 0.5 ml of undiluted D4 was applied to the shaved skin (intact and abraded) of 6 albino rabbits for 24 hours. There was no information on the type of dressing used to hold the D4 in place. The animals were then observed for 72 hours for skin reactions and signs of toxicity. Skin reactions were scored according to the scoring system of Draize. No skin reactions were observed at any time in intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours. Therefore D4 was not irritating to the skin under the conditions of this study. The study was conducted according to a protocol similar to OECD TG 404, but not in compliance with GLP.

Supporting studies confirm the conclusion that D4 is not a skin irritant.

The second skin irritation study was read-across from the structural analogue decamethylcyclopentasiloxane D5 (CAS 541-02-6). The study was conducted according to OECD TG 404 and in compliance with GLP. New Zealand white rabbits (3 animals/sex) were dermally exposed to undiluted D5 under a semi-occlusive dressing for 24 hours. On each animal there was one intact application site and one abraded site. The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance. Throughout the test, animals were observed for signs of toxicity. Skin reactions were graded according to the Draize grading system. There were no signs of toxicity or irritation and animals gained weight as expected. There are two reliable supporting studies (Proctor & Gamble, 1985; Unknown, 1975) available for skin irritation, which confirm the conclusion that D5 is not irritating to skin.

The first eye irritation study was read-across from D4, (CAS 556-7-2). In this study (Dow Corning Corporation, 1997) 0.1 ml of undiluted D4 was administrated into the right eye of each of three New Zealand white rabbits. The eyes were rinsed with lukewarm water 24 hours after instillation, and were then scored for irritation at 1, 24, 48 and 72 hours following test substance administration. D4 was determined not irritating to eyes under the conditions of this study. The study was conducted according to an appropriate OECD TG 405, and in compliance with GLP.

The second eye irritation study was read-across from the structural analogue decamethylcyclopentasiloxane, D5 (CAS 541-02-6). The study was conducted according to OECD TG 405, and in compliance with GLP. New Zealand white rabbits (3 animals/sex) had 0.1ml undiluted D5 instilled into one of their eyes. Eyes were examined at 24, 48 and 72 hours after treatment. Animals were also observed for signs of toxicity throughout the test. No overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any of the observation points. There are two reliable supporting studies (Carnegie-Mellon, 1976; Springborn Institute for Bioresearch, Inc, 1977) available for eye irritation, which confirm the conclusion that D5 is not irritating to eyes.

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 and eye irritation. 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 (CAS 556-67-2) 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 physiological temperature 35ºC and pH 7 (relevant for conditions in the eyes), the hydrolysis half- life is calculated as 25 hours. The product of hydrolysis is dimethylsilanediol. 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 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. The hydrolysis half-life of D5 at 35ºC and pH 7 (relevant for eyes) is 590 hours. 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.

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 7		Component 1 Vi5 -D5 600 h at 37.5 ºC  Component 2 Vi5 -D4 23 h at 37.5 ºC		25 h at 35ºC		590 at 35ºC
Hydrolysis half-life at pH 5		Component 1 Vi5 -D5 > 1.5 min < 600 h at 37.5 ºC  Component 2 Vi5 -D4 > 15 sec < 23 h at 37.5 ºC		< 0.9 h < 25 h at 35ºC		< 4.3 h < 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		0.017 mg/l at 23°C

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

The first skin irritation 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 study (Laboratoires de Recherches de la Societe des Usines, 1971) 0.5 ml of undiluted D4 was applied to the shaved skin (intact and abraded) of 6 albino rabbits for 24 hours. There was no information on the type of dressing used to hold the D4 in place. The animals were then observed for 72 hours for skin reactions and signs of toxicity. Skin reactions were scored according to the scoring system of Draize. No skin reactions were observed at any time in intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours. Therefore D4 was not irritating to the skin under the conditions of this study. Supporting studies confirm the conclusion that D4 is not a skin irritant.

The second skin irritation study was read-across from the structural analogue decamethylcyclopentasiloxane D5 (CAS 541-02-6). The study was conducted according to OECD TG 404 and in compliance with GLP. New Zealand white rabbits (3 animals/sex) were dermally exposed to undiluted D5 under a semi-occlusive dressing for 24 hours. On each animal there was one intact application site and one abraded site. The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance. Throughout the test, animals were observed for signs of toxicity. Skin reactions were graded according to the Draize grading system. There were no signs of toxicity or irritation and animals gained weight as expected. There are two reliable supporting studies (Proctor & Gamble, 1985; Unknown, 1975) available for skin irritation, which confirm the conclusion that D5 is not irritating to skin.

The first eye irritation study was read-across from 556-7-2. The study was conducted according to an appropriate OECD Test Guideline and in compliance with GLP.  In this study (Dow Corning Corporation, 1997) 0.1 ml of undiluted D4 was administrated into the right eye of each of three New Zealand white rabbits. The eyes were rinsed with lukewarm water 24 hours after instillation, and were then scored for irritation at 1, 24, 48 and 72 hours following test substance administration. D4 was determined not irritating to eyes under the conditions of this study.

The second eye irritation study was read-across from the structural analogue decamethylcyclopentasiloxane (CAS 541-02-6). The study was conducted according to OECD TG 405 and in compliance with GLP. New Zealand white rabbits (3 animals/sex) had 0.1ml undiluted D5 instilled into one of their eyes. Eyes were examined at 24, 48 and 72 hours after treatment. Animals were also observed for signs of toxicity throughout the test. No overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any of the observation points. There are two reliable supporting studies (Carnegie-Mellon, 1976; Springborn Institute for Bioresearch, Inc, 1977) available for eye irritation, which confirm the conclusion that D5 is not irritating to eyes.

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 and eye irritation 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 under the conditions of an irritation study 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 and eye irritation studies 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 >95% and no impurities are present at >1%.

The test substances in the skin and eye irritation studies with the second source substance D5, have a purity of >95%.

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

Not relevant.

References:

Carnegie-Mellon Institute of Research Chemical Hygiene Fellowship. (1976). Miscellaneous Toxicity Studies. Testing laboratory: Carnegie-Mellon Institute of Research Chemical Hygiene Fellowship. Report no.: Special Report 39-62. Report date: 1976-06-10.

Proctor & Gamble. (1985). Rabbit skin irritation (closed patch test). Testing laboratory: The Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45347. Owner company: Proctor & Gamble. Study number: B85-0294. Report date: 1985-07-17.

Springborn Institute for Bioresearch, Inc. (1977b). Draize eye irritation of the test material T7095 in rabbits. Testing laboratory: Springborn Institute for Bioresearch, Inc., 553 North Broadway, Spencerville, Ohio 45887. Report no.: 77-291. Report date: 1977-12-30.

Unknown. (1975). Rabbit Skin Irritation (SL: V3948-107). Report no.: BSBTS 293. Owner company: Proctor & Gamble. Report date: 1975-12-09.

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 and eye irritation based on Regulation (EC) No. 1272/2008.