S-(1-oxidotetrahydro-3-thiophen-yl)ethanethioate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

1- Software:
Derek Nexus

2- Model:
Lhasa Limited

3- SMILES or other identifiers used as input for the model :
Ethanethioic acid, S-​[(1R,​3S)​-​tetrahydro-​1-​oxido-​3-​thienyl] ester

4- SCIENTIFIC VALIDITY OF THE QSAR MODEL:
these above mentioned tools were selected according to the OECD Guidance Document on the validation of QSAR models:
Document on the validation of (Quantitative) structure Activity Relationship models. OECD Series on testing and assessment n° 69. ENV/ JM/MONO(2007)2

5- Applicability Domain:
The prediction is generated by applying expert knowledge rules in toxicology to the data returned fromm the knowledge base

6- Adequacy of the result:
Skin sensitisation is PLAUSIBLE

Data source

Reference

Reference Type:

other: QSAR in silico prediction

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Series on Testing and Assessment n° 69

Version / remarks:

ENV/JM/MONO(2007)2

Deviations:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

S-(1-oxidotetrahydro-3-thiophen-yl)ethanethioate

EC Number:

601-737-6

Cas Number:

120788-03-6

Molecular formula:

C6H10O2S2

IUPAC Name:

S-(1-oxidotetrahydro-3-thiophen-yl)ethanethioate

Results and discussion

In vitro / in chemico

Results

Parameter:

other: QSAR prediction is not a in vitro/in chemico study

Remarks:

QSAR prediction is not a in vitro/in chemico study

Remarks on result:

other: QSAR prediction Skin sensitiser

In vivo (non-LLNA)

Results

Reading:

other: QSAR prediction- it is not an In vivo (non-LLNA)study

Remarks on result:

other: QSAR prediction skin sensitiser

In vivo (LLNA)

Results

Parameter:

other: QSAR prediction- It is not an In vivo (LLNA) study

Remarks on result:

other: QSAR prediction skin sensitiser

Any other information on results incl. tables

This study was designated to generate estimated "in silico" data to be used for the hazard assessment of the substance.

the table below shows the result obtained:

Endpoint	Derek Nexus prediction
Skin sensitisation	plausible

Skin sensitisation: guinea pig maximisation test (GPMT), human patch test.

Potential mechanism (dithioester): Hapten acting as an electrophilic thioacylating agent [Payne and Walsh].

Potential mechanism (thiol): Pre/prohapten producing a nucleophilic thiol exchange compound [Payne and Walsh].

Thioesters for which R1 = S induce skin sensitisation by directly acylating skin proteins [Payne and Walsh]. In contrast, thioesters for which R1 = O are likely to induce skin sensitisation as a result of hydrolysis to the corresponding thiol, which may then undergo thiol exchange with disulphide bridges present in skin proteins. Evidence for this latter mechanism comes from studies with the topical corticosteroid tixocortol pivalate, which has been shown to give positive responses in the GPMT and in human patch testing [Bruze et al, Isaksson et al, Wilkinson]. In addition to in vitro studies which have demonstrated the binding of tixocortol pivalate to protein via disulphide bridges, cross-reactivity of this compound with other topical corticosteroids such as hydrocortisone has been established [Isaksson et al, Wilkinson].

Thiobenzoylsulphanyl-acetic acid and (4-acetylamino-thiobenzoylsulphanyl)-acetic acid have also both produced positive responses in the GPMT [Cronin and Basketter].

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

skin sensitisation:

Prediction : plausible

Executive summary:

The skin sensitisation of the target compound was predicted employing an in silico approach: the decision rule system provided by Derek Nexus.

The predictor was employed in order to apply a weight of evidence approach. In the case of the target S-[(1R, 3S)-1 -oxidotetrahydrothiophrn-3 -yl ]ethanethioate Derek Nexus predicted the skin sensistisation as plausible.