3-(dimethoxymethylsilyl)propanethiol

Endpoint summary

Description of key information

There were no data for irritation 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 irritation, conducted according to a test protocol that is comparable to the appropriate OECD test guideline, but not in compliance with GLP, found 3-trimethoxysilylpropane-1-thiol not irritating to the skin of New Zealand white rabbits (BRRC, 1990).

The key study for eye irritation, conducted according to a test protocol that is comparable to the appropriate OECD test guideline, but not in compliance with GLP, found 3-trimethoxysilylpropane-1-thiol not irritating to the eyes of New Zealand white rabbits (BRRC, 1990).

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

The key study for skin irritation (BRRC, 1990) applied the undiluted test material (0.5 ml) to the intact (shaved) skin of six New Zealand white rabbits for four hours under an occlusive dressing. The dressings were then removed, the skin washed and the skin reactions observed for up to 14 days. None of the rabbits had any signs of skin irritation, and no other clinical signs of toxicity were observed. It was therefore concluded by the study authors that the test substance was not irritating to the skin.

The key study for eye irritation (BRRC, 1990) instilled the test material into the lower conjunctival sac of one eye per rabbit (six rabbits per volume). The eyelids were held together for one second. The eyes were scored, by a scoring system similar to that recommended in OECD test guideline 405, at one, four and 24 hours, 2, 3 and 7 days after dosing. Additional readings were made, if necessary, at 14 and 21 days. Fluorescein (2%) staining was used to determine corneal injury before dosing and one day after instillation. No corneal injury or iritis was observed in any of the eyes. Within one hour minor transient conjunctival irritation (redness) was observed in 5/6 animals from the 0.1 ml group. All eyes were normal within 48 hours. Therefore overall the test substance was not irritating to eyes.

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. At the pH of the skin and eye 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0) and 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1) both hydrolyse rapidly. They share the common hydrolysis product methanol, which does not contribute to any adverse effects for irritation 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 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 containing a thiol functional group. Both contain a silicon atom 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)propanethiol and 3-(trihydroxysilyl)propanethiol, and the same non-silicon hydrolysis product, methanol.

After hydrolysis, the dermal absorption of the silicon hydrolysis products is comparable, based on the log K_ow of 0.5 and -1.4 of the target and source substances respectively. There are no structural features which suggest increased irritation potential. A typical dissociation constant of a thiol group is 11-12, with no expected pH-related irritancy.

(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: 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-[dimethoxy)methyl)silyl]propane-1-thiol	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 irritation properties of the non-silanol hydrolysis products

The non-silanol hydrolysis product, methanol does not contribute to any irritant effects at the relevant concentrations based on publicly available information.

References:

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

 

Justification for classification or non-classification

Based on the available data on the read-across substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0), the registered substance does not require classification for irritation according to Regulation (EC) No 1272/2008.