Reaction mass of 2,2'-thiodiethanethiol and 1095071-01-4 and α-sulfanyl-ω-{2-[(2-sulfanylethyl)sulfanyl]ethyl}bis[ethane- 1,2-diylsulfanediylethane- 1,2-diylsulfanediyl(3-hydroxypropane-1,1-diyl) sulfanediyl]

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

Standard Draize test

Type of information:

(Q)SAR

Adequacy of study:

key study

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE: ACD Labs/Percepta (2016 Release).

2. MODEL: ACD/Percepta: Eye Irritation

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C18H38O2S9
Structural codes:
a. SMILES: SCCSCCSC(CCO)SCCSCCSC(CCO)SCCSCCS
b. InChI: InChI=1S/C18H38O2S9/c19-3-1-17(26-13-9-23-7-5-21)28-15-11-25-12-16-29-18(2-4-20)27-14-10-24-8-6-22/h17-22H,1-16H2
c. Other structural representation: mol file used and included in the test material information.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Eye irritation/corrosion
- Unambiguous algorithm: Binomial PLS probabilistic model supplemented by an expert system that identifies structural alerts relevant to irritating properties of compounds (see attached QMRF for further details).
- Defined domain of applicability: Detailed structural and/or response limits of the applicability domain are not defined. However, for each prediction, a list of all the rules (alerts) applicable to the calculation of irritation potential of the target molecule is provided, as well as the percentage of training set chemicals containing these alerts and exhibiting moderate or stronger eye irritation. In addition, the software displays up to five most similar structures from the training set along with experimental results.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please see attached QMRF.
- Mechanistic interpretation: The structural alerts used for classifying chemicals were derived from existing mechanistic knowledge. Fragmental descriptors used in the analysis have been predefined to represent certain features of the compounds known to be related to their eye irritating properties, e.g. high acidity, basicity, electrophilicity, etc.

5. APPLICABILITY DOMAIN
For the target HIDT-adduct, five structural analogues were identified in the training set, suggesting that the target is included in the applicability domain of the model. No structural alerts for eye irritation were identified.
-descriptor domain: not applicable.
-structural fragment domain: not applicable.
-mechanism domain: not applicable.
Please see attached QPRF for structural analogues and further details.

6. ADEQUACY OF THE RESULT
The target HIDT-adduct was predicted negative for eye irritation/corrosion in standard rabbit Draize test based on a predicted probability to cause severe/moderate eye irritation equal to 0.21. The prediction was assessed as moderate reliable. This QSAR prediction indicated an absence of eye irritation/corrosion potential for the target HIDT-adduct and could be used in a weight of evidence approach to support the conclusion of no classification.
This negative eye irritation QSAR prediction was assessed as adequate for regulatory purposes.

Data source

Reference

Reference Type:

other: Software

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6 (2008)

Principles of method if other than guideline:

- Software tool(s) used including version: ACD/Labs (2016 release)
- Model(s) used: ACD/Percepta Eye Irritation
- Model description: see field 'Justification for type of information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification'

Test material

Test material information

Constituent 1

Reference substance name:

7-(2-hydroxyethyl)-1-sulfanyl-15-({2-[(2-sulfanylethyl)sulfanyl]ethyl}sulfanyl)-3,6,8,11,14-pentathiaheptadecan-17-ol

Molecular formula:

C18H38O2S9

IUPAC Name:

7-(2-hydroxyethyl)-1-sulfanyl-15-({2-[(2-sulfanylethyl)sulfanyl]ethyl}sulfanyl)-3,6,8,11,14-pentathiaheptadecan-17-ol

Specific details on test material used for the study:

SMILES: SCCSCCSC(CCO)SCCSCCSC(CCO)SCCSCCS
InChI=1S/C18H38O2S9/c19-3-1-17(26-13-9-23-7-5-21)28-15-11-25-12-16-29-18(2-4-20)27-14-10-24-8-6-22/h17-22H,1-16H2

Test animals / tissue source

Species:

rabbit

Results and discussion

In vivo

Results

Irritation parameter:

other: Probability to cause severe/moderate eye irritation = 0.21

Remarks on result:

no indication of irritation

Remarks:

Based on QSAR prediction

Any other information on results incl. tables

The uncertainty of the prediction was evaluated considering the following aspects: i) positive predicted probability; ii) identified structural alerts; iii) similarity of the target compound to the training set and consistency of experimental values for similar compounds.

Limited uncertainty was associated with the negative eye irritation prediction due to the following considerations:

- five structural analogues with moderate similarity were identified in the training set,

- the identified structural analogues had consistent negative experimental data (even if their prediction accuracy is not adequate).

Overall, eye irritation prediction was assessed as moderate reliable.

Applicant's summary and conclusion

Interpretation of results:

other: This QSAR prediction could be used to support the conclusion of no classification.

Conclusions:

The target HIDT-adduct was predicted negative for eye irritation/corrosion in standard rabbit Draize test based on a predicted probability to cause severe/moderate eye irritation equal to 0.21. The prediction was assessed as moderate reliable. This QSAR prediction indicated an absence of eye irritation/corrosion potential for the target HIDT-adduct and could be used in a weight of evidence approach to support the conclusion of no classification. This eye irritation QSAR prediction was assessed as adequate for regulatory purposes.

Executive summary:

This study was designed to generate in silico (non-testing) data of eye irritation for HIDT-adduct. A reliability score of 2 was assigned, since results derived from a valid (Q)SAR model, falling into its applicability domain, with adequate and reliable documentation/justification.

The eye irritation model implemented in ACD/Percepta (2016 Release) was employed, which estimates the potential of a chemical to cause eye irritation in a standard rabbit Draize test. The cut-off value for positive/negative eye irritation predictions is 0.5.

ACD/Percepta eye irritation model predicted the target HIDT-adduct as not eye irritant, based on a probability of severe/moderate irritation equal 0.21. The uncertainty of the prediction was evaluated considering the following aspects: i) positive predicted probability; ii) identified structural alerts; iii) similarity of the target compound to the training set and consistency of experimental values for similar compounds.

Limited uncertainty was associated with the negative eye irritation prediction generated for the target HIDT-adduct based on the following considerations: five structural analogues with moderate similarity were identified in the training set; ii) the identified structural analogues had consistent negative experimental data (even if their prediction accuracy is not adequate).

Overall, the negative eye irritation prediction was assessed as moderately reliable and adequate for regulatory purposes.