3-(dimethoxymethylsilyl)propanethiol

Endpoint summary

Description of key information

There were no data for sensitisation for the registered substance. Data are read across from the analogous substance 3 -trimethoxysilylpropane-1 -thiol (CAS 4420-74-0).

The key study for skin sensitisation (Hüls, 1998) conducted according to OECD test guidelines (Buehler test) and GLP, found 3-trimethoxysilylpropane-1-thiol sensitising to the skin of Dunkin-Hartley guinea-pigs.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

There data for sensitisation are read across from the analogous substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0).

3-trimethoxysilylpropane-1-thiol was tested in a traditional Buehler skin sensitisation study, to GLP (Hüls, 1998). The test and control animals showed normal body weight gains throughout the study. No clinical signs of systemic effects were observed in any of the animals during the observation period. There were no skin reactions following induction Phase I. Following Phases II and III there was moderate to severe skin reactions. The control animals treated with the vehicle only, did not show any irritation after all three inductions. Following the challenge application there were skin reactions in eight animals: 30 hours post-application the animals had moderate to intense erythema and swelling; at 54 hours patchy to intense erythema and swelling. All 12 other test, and all control animals did not show any skin reactions 30 -54 hours after treatment. Therefore the study authors concluded that 3-trimethoxysilylpropane-1-thiol is a skin sensitiser.

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 acute toxicity, irritation, sensitisation and genotoxicity endpoints relevant properties are physicochemical properties, structural similarity and hydrolysis rate. In the following paragraphs the proposed read-across for the above endpoints from 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0) to 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1) is evaluated point by point. Additional information is given in a supporting report (PFA 2014ap) attached in Section 13.

Read-across hypothesis

The hypothesis is that source (read-across) and target (registration) substances have comparable toxicological properties because they contain an identical propanethiol sidechain attached to silicon and hydrolyse to analogous silicon-containing hydrolysis products. They share the common hydrolysis product methanol, which does not contribute to any adverse effects for sensitisation based on publicly available information. This is discussed further below.

 

Read-across justification

The predicted half-lives at 20 -25°C of the registered substance, 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1), are 1.4 hours at pH 7, 0.1 hours at pH 4, and 0.03 hours at pH 9 and 20-25°C (QSAR). The products of hydrolysis are 3-(dihydroxymethylsilyl)propanethiol and methanol.

The read-across substance, 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0), has a predicted hydrolysis half-life of 2.6 hours at pH 7, 0.2 hours at pH 4, 0.1 hours at pH 9 and and 20-25°C (QSAR). The products of hydrolysis are 3-(trihydroxysilyl)propanethiol and methanol.

 

Analogue approach justification

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkoxysilane substances. Both contain a silicon atom to which is attached to a propanethiol side chain. The propanethiol side chains of the two substances are identical. The registered substance has two methoxy groups and a methyl group bound to silicon. The only difference in the read across substance is that all three groups bound to the silicon are methoxy groups. Both hydrolyse rapidly to produce similar silicon-containing hydrolysis products, 3-(dihydroxymethylsilyl)propanethioland 3-(trihydroxysilyl)propanethiol, and the same non-silicon hydrolysis product, methanol.

(b) Similar physicochemical characteristics

The key physicochemical parameters are summarised below. The similarity of the hydrolysis rates at pH relevant to oral exposure is important. Both parent substances are soluble in water, have low log K_ow and comparable vapour pressure; they are of similar molecular weight.

Table 5.6.3: Key physicochemical parameters

	Target (registration substance)	Source (read-across substance)
CAS Number	31001-77-1	4420-74-0
EC number	250-426-8	224-588-5
Chemical Name	3-(dimethoxymethylsilyl)propanethiol	3-trimethoxysilylpropane-1-thiol
Purity	>99%	>98%
Impurities	Siloxane, alkoxysilane	Organosilane and siloxane, methanol
Molecular weight (gmol^-1)	180.34	196.34
log Kow (parent)	2.9 at 20°C (QSAR)	1.7 at 20°C (QSAR)
log Kow (silanol hydrolysis product)	0.5 at 20°C (QSAR)	-1.4 at 20°C (QSAR)
Water solubility (parent)	290 mg/l at 20°C (QSAR)	2.8E+03 mg/l at 20°C (QSAR)
Water solubility (silanol hydrolysis product)	47000 mg/l at 20°C (QSAR) (limited by condensation reactions)	1E+06 mg/l at 20°C (QSAR) (limited by condensation reactions)
Vapour pressure (parent)	23 Pa at 25°C (QSAR)	8.1 Pa at 25°C (QSAR)
Vapour pressure (silanol hydrolysis product)	0.0092 Pa at 25°C (QSAR)	1.5E-04 Pa at 25°C (QSAR)
Hydrolysis t1/2at pH 7 and 20-25°C	1.4 h	2.6 h
Hydrolysis t1/2at pH 2 and 37.5°C (relevant for oral exposure)	5 seconds	5 seconds

 

(c) Discussion of toxicity of the non-silanol hydrolysis products

 

The sensitisation potential of the non-silanol hydrolysis product, methanol, has been summarised by OECD (2004). It is beyond the scope of this assessment to review all of the available data in detail. However, the key findings from the disseminated REACH dossiers and OECD SIAR reports (OECD 2004) are reported here to support read-across arguments. Details are available for a study in which methanol is assessed in a guinea pig maximisation test, with no evidence of sensitisation potential.

References:

OECD (2004): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 18-20 October 2004, Methanol, CAS 67-56-1.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, on the analogous read-across substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0), the registered substance is classified as sensitising, Skin Sensitisation Category 1B; H317: May cause an allergic skin reaction, according to Regulation (EC) No 1272/2008.