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Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
Based on expert system - decision tree
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
Justification for type of information:
1. SOFTWARE: Toxtree v. 2.6.13

2. MODEL: Toxtree: Skin Irritation/corrosion

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C28H46O13S6
Structural codes:
a. SMILES: SCCC(=O)OCC(COC(=O)CCS)(COC(=O)CCS)COCC(COC(=O)CCS)(COC(=O)CCS)COC(=O)CCS
b. InChI: InChI=1S/C28H46O13S6/c29-21(1-7-42)36-15-27(16-37-22(30)2-8-43,17-38-23(31)3-9-44)13-35-14-28(18-39-24(32)4-10-45,19-40-25(33)5-11-46)20-41-26(34)6-12-47/h42-47H,1-20H2
c. Other structural representation: mol file used and included in the test material information.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Skin irritation/corrosion
- Unambiguous algorithm: Decision tree by physico-chemical property ranges and structural alert rules (Skin Irritation Corrosion Rules Estimation Tool - SICRET). No mathematical algorithms have been established since the (Q)SAR rules are not calculated, but based on measured data.(See attached QMRF for further details).
- Defined domain of applicability: Not applicable
- Appropriate measures of goodness-of-fit and robustness and predictivity: Not applicable.
- Mechanistic interpretation: Classification rules based on limit values for physicochemical data: this method doesn't have a clear mechanistic basis but reflects the
chemical reactivity of the chemical substance when in contact with skin. Classification rules based on structural alerts: the alerts were gathered for chemicals with skin irritation or skin corrosion potential. The structural alerts used to identify chemicals with skin irritation or corrosion potential were selected a priori from existing mechanistic
knowledge (based on measured data).

5. APPLICABILITY DOMAIN
Applicability domain of this decision tree is not defined.
- descriptor domain: not applicable.
- structural fragment domain: not applicable.
- mechanism domain: not applicable.

Please see attached QPRF for further details.

6. ADEQUACY OF THE RESULT
di-PETMP was predicted negative for skin irritation/corrosion based on the exceedance of the melting point physico-chemical limit, which corresponds to 200°C, as implemented in the decision tree of Toxtree. The prediction was assessed as moderate reliable. This QSAR prediction indicated a negative skin irritation/corrosion potential of the target di-PETMP and could be used to support the conclusion for no classification.
This skin irritation QSAR prediction was assessed as adequate for regulatory purposes.

Data source

Reference
Reference Type:
other: Software
Title:
Toxtree v. 2.6.13, skin irritation/skin corrosion.
Author:
Ideaconsult Ltd
Year:
2005
Bibliographic source:
[1] Gerner et al. (2004) QSAR Comb. Sci.,23:726-733 [2] Hulzebos et al. (2005) QSAR Comb. Sci.,24:332-342. [3] Walker et al. (2005) QSAR Comb. Sci., 24:378-384.

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:Toxtree v. 2.6.13
- Model(s) used: Toxtree v. 2.6.13, skin irritation/skin corrosion
- 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

Constituent 1
Chemical structure
Reference substance name:
2-[[3-(3-mercapto-1-oxopropoxy)-2,2-bis[(3-mercapto-1-oxopropoxy)methyl]propoxy]methyl]-2-[(3-mercapto-1-oxopropoxy)methyl]propane-1,3-diyl bis[3-mercaptopropionate]
EC Number:
246-893-2
EC Name:
2-[[3-(3-mercapto-1-oxopropoxy)-2,2-bis[(3-mercapto-1-oxopropoxy)methyl]propoxy]methyl]-2-[(3-mercapto-1-oxopropoxy)methyl]propane-1,3-diyl bis[3-mercaptopropionate]
Cas Number:
25359-71-1
Molecular formula:
C28H46O13S6
IUPAC Name:
3-[(3-sulfanylpropanoyl)oxy]-2-[(3-[(3-sulfanylpropanoyl)oxy]-2,2-bis{[(3-sulfanylpropanoyl)oxy]methyl}propoxy)methyl]-2-{[(3-sulfanylpropanoyl)oxy]methyl}propyl 3-sulfanylpropanoate (non-preferred name)
Specific details on test material used for the study:
SMILES: SCCC(=O)OCC(COC(=O)CCS)(COC(=O)CCS)COCC(COC(=O)CCS)(COC(=O)CCS)COC(=O)CCS
InChI=1S/C28H46O13S6/c29-21(1-7-42)36-15-27(16-37-22(30)2-8-43,17-38-23(31)3-9-44)13-35-14-28(18-39-24(32)4-10-45,19-40-25(33)5-11-46)20-41-26(34)6-12-47/h42-47H,1-20H2

Test animals

Species:
rabbit

Results and discussion

In vivo

Results
Irritation parameter:
other: Not irritating or corrosive to the skin (for the target a physico-chemical property exclusion rule was fulfilled, i.e. melting point (MP) greater than 200°C.)
Remarks on result:
no indication of irritation
Remarks:
Based on (Q)SAR prediction

Any other information on results incl. tables

The uncertainty of the prediction was evaluated considering the following aspects associated with the applicability domain: i) physico-chemical rules; ii) structural rules/alerts.

Based on these considerations, an overall limited uncertainty was attributed to the negative skin irritating/corrosive prediction generated for di-PETMP.

Applicant's summary and conclusion

Interpretation of results:
other: This QSAR prediction could be used to support the conclusion for no classification.
Conclusions:
di-PETMP was predicted negative for skin irritation/corrosion based on the exceedance of the melting point physico-chemical limit, which corresponds to 200°C, as implemented in the decision tree of Toxtree. The prediction was assessed as moderate reliable. This QSAR prediction indicated a negative skin irritation/corrosion potential of the target di-PETMP and could be used to support the conclusion for no classification.
Executive summary:

This study was designed to generate estimated in silico (non-testing) data of skin irritation/corrosion for Dipentaerythritol hexa(3-mercaptopropionate) (di-PETMP). A reliability score of 2 was assigned to the prediction, since results were derived from a valid (Q)SAR model. The skin irritation model implemented in Toxtree v 2.6.13 was employed, which estimates the potential of a chemical to cause skin irritation based on expert rule-based decission tree. A physico-chemical property exclusion rule, i.e. melting point (MP) greater than 200°C was fullfield for the target i.e. the estimated MP value of the target (349.84°C, EPI Suite) exceeded the property limit of 200°C, thus suggesting a lack of skin irritation or corrosion potential for the target di-PETMP.

Uncertainty of the prediction was evaluated considering the following aspects associated with the applicability domain: i) physico-chemical rules; ii) structural rules/alerts. An overall limited uncertainty was attributed to the negative skin irritating/corrosive prediction generated for di-PETMP, which was then assessed as moderate reliable. The skin irritation prediction was thus assessed as adequate for regulatory purposes.