1,1,5,5,5-hexamethyl-3-phenyl-3-[(trimethylsilyl)oxy]trisiloxane

Endpoint summary

Description of key information

The key skin irritation study was read-across from the structurally analogous substances 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2). A supporting study, read-across from 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), was also available. The studies, conducted according to OECD TG 404, and in compliance with GLP, report the substances, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), to be not irritating to skin (LPT, 2002).

The key eye irritation study was read-across from the structurally analogous substances 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2). A supporting study, read-across from 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), was also available. Both studies were conducted according to OECD TG 405, and in compliance with GLP, and report the substances, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), to be not irritating to eyes (LPT, 2002).

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 key skin irritation study is read-across from the structurally analogous substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2). The study, conducted according to OECD test guideline 404, and in compliance with GLP, reports the substance, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2), to be not irritating to skin (LPT, 2002).

Following application of 0.5 mL of test material onto rabbit skin for 4 hours, kept in contact with the skin under semi-occlusive dressing, very slight erythema was observed at 60 minutes post-application. The erythema was fully reversible within 24 hours. There were no signs of oedema in any of the animals during the observation period of 14 days. No other signs of toxicity were noted.

A supporting skin irritation study is read-across from the structurally analogous substance 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9). The study, conducted according to OECD TG 404, and in compliance with GLP, reports the substance, 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), to be not irritating to skin (LPT, 2002).

Following application of 0.5 mL of test material onto rabbit skin for 4 hours, kept in contact with the skin under semi-occlusive dressing, no erythema or oedema were observed in any of the animals during the 14 day study period.

The key eye irritation study is read-across from the structurally analogous substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2). The study, conducted according to OECD TG 405, and in compliance with GLP, reports the substance, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2), to be not irritating to eyes (LPT, 2002).

Following a single instillation of 0.1 mL of test material into the right eye of 3 rabbits, the cornea, iris and conjunctivae were not affected by the test substance. No signs of irritation/ corrosion were noted during the study period.

A supporting eye irritation study is read-across from the structurally analogous substance 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9). The study, conducted according to OECD TG 405, and in compliance with GLP, reports the substance, 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), to be not irritating to eyes (LPT, 2002).

Following a single instillation of 0.1 mL of test material into the eyes of 3 rabbits, grade 1 corneal opasity was observed at 24 hours post-treatment in 2 of the animals, which was fully reversible within 48 hours. The iris and conjunctivae were not affected by the test substance in any of the animals. No other signs of irritation/ corrosion were noted during the study period.

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. In the case of irritation, the relevant properties are structural similarity and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across from 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) to the registered substance, tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9), is evaluated point by point.

Read-across hypothesis

The hypothesis is that the target (registration) substance and the source (read-across) substances have similar toxicological properties because they are structurally similar and hydrolyse at comparable rates to similar silanol hydrolysis products:

• Phenylsilanetriol and trimethylsilanol (registered substance);

• Diphenyl(methyl)silanol and methyl(phenyl)silanediol (1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane) and

• Diphenyl(methyl)silanol and dimethylsilanediol 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane).

Read-across justification

The predicted hydrolysis half-lives of the registered substance, tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9), are >1.9 h at pH 4, >200 h (>8.3 d) at pH 7 and >2.0 at pH 9 and 20-25°C (QSAR). At pH 4 (closest to the known pH of the skin, 5.5), the hydrolysis rate is >1.9 h. The products of hydrolysis are phenylsilanetriol and trimethylsilanol.

The read-across substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) has predicted hydrolysis half-lives of >200 h at pH 7, approximately 1.9 h at pH 4, 1.4 h at pH 5, and 2.0 h at pH 9 and 25°C. The products of hydrolysis are diphenyl(methyl)silanol and methyl(phenyl)silanediol.

The read-across substance 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) has predicted hydrolysis half-lives of >200 h at pH 7, approximately 1.9 h at pH 4, 1.4 h at pH 5, and 2.0 h at pH 9 and 25°C. The products of hydrolysis are dimethylsilanediol and diphenyl(methyl)silanol.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered.

Analogue approach justification

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkoxysilanes and silanols. All three substances are linear or branched siloxanes. All silicon atoms present are fully substituted with methyl and phenyl groups. The registration substance, tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9) is a branched siloxane chain with four silicon atoms, connected by three oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with three methyl or one phenyl group.

The read-across substances are both linear siloxanes, with three silicon atoms connected by two oxygen atoms. The terminal silicon atoms are substituted with two phenyl and one methyl group. The substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) has one methyl and one phenyl groups on the central silicon atom; 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) has two methyl groups on the central silicon atom.

All three substances produce phenyl and/or methyl substituted silicon hydrolysis products. See table below for detail of hydrolysis products.

Si hydrolysis products of submission substance and relevant read-across substances

Substance
	Phenylsilanetriol	Diphenyl(methyl)silanol	Methyl(phenyl)silanediol	Trimethylsilanol	Dimethylsilanediol
Tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9)	Yes	-	-	Yes	-
1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2)	-	Yes	Yes	-	-
1,3,3,5-Tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9)	-	Yes	-	-	Yes

(b) Similar physicochemical characteristics

Structural similarity and physicochemical properties are relevant to the skin irritation potential of a substance. The parent substances hydrolyse at a similar rate and to similar silanol hydrolysis products. The key physicochemical parameters are summarised below.

Table 5.2.3: Key physicochemical parameters

	Target (registration substance)	Source (read-across substance)	Source (read-across substance)
CAS number	2116-84-9	3390-61-2	3982-82-9
EC number	218-320-6	222-222-9	223-620-5
Chemical Name	tris(trimethylsiloxy)phenylsilane	1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane	1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane
Molecular weight  (gmol^-1)	156.21	546.89	484.82
log Kow(parent)	9.0 at 20°C (QSAR)	9.0 at 20°C (QSAR)	9.0 at 20°C (QSAR)
Water solubility (parent)	0.0066 mg/l at 23°C (measured)	9.0E-11 mg/l at 23°C (QSAR)	5.9E-09 mg/l at 23°C (QSAR)
Water solubility (silicon-containing hydrolysis products)	The concentration dissolved in water is limited to about 1000 mg/l by condensation reactions	9 E-11 mg/l at 20-25°C (QSAR)	5.9E-09 mg/l at 20-25°C (QSAR)
Hydrolysis at pH 4, 20-25°C	>1.9 h	>1.9 h	>1.9 h
Vapour pressure (parent)	0.09 Pa at 25°C (QSAR)	1.3E-08 Pa	5.9E-07 Pa

(c) Discussion of the hydrolysis rates of the substances

The predicted half-lives for the registration substance tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9) (between >0.7 and 70 h) and the read-across substances 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) at pH 5.5 are comparable. All three substances will be hydrolysed to similar silanol hydrolysis products.

Based on the structural similarity and similar physicochemical properties of the silicon hydrolysis products, their irritancy potential is expected to also be similar. Therefore, the read-across is considered valid.

Justification for classification or non-classification

Based on the available data on read-across substances, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), no classification for skin and eye irritation/ corrosion is required for the registered substance according to Regulation (EC) No. 1272/2008.