(2,4,6-trioxo-1,3,5-triazine-1,3,5(2H,4H,6H)-triyl)triethane-2,1-diyl tris(3-mercaptopropionate)

Skin irritation / corrosion

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: C18H27N3O9S3
Structural codes:
a. SMILES: O=C(OCCn1c(=O)n(c(=O)n(CCOC(=O)CCS)c1=O)CCOC(=O)CCS)CCS
b. InChI: InChI=1S/C18H27N3O9S3/c22-13(1-10-31)28-7-4-19-16(25)20(5-8-29-14(23)2-11-32)18(27)21(17(19)26)6-9-30-15(24)3-12-33/h31-33H,1-12H2
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
TEMPIC 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 moderately reliable. This QSAR prediction indicated a negative skin irritation/corrosion potential of the target TEMPIC 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

Test material information

Constituent 1

Reference substance name:

(2,4,6-trioxo-1,3,5-triazine-1,3,5(2H,4H,6H)-triyl)triethane-2,1-diyl tris(3-mercaptopropionate)

EC Number:

252-907-8

EC Name:

(2,4,6-trioxo-1,3,5-triazine-1,3,5(2H,4H,6H)-triyl)triethane-2,1-diyl tris(3-mercaptopropionate)

Cas Number:

36196-44-8

Molecular formula:

C18H27N3O9S3

IUPAC Name:

2-[2,4,6-trioxo-3,5-bis({2-[(3-sulfanylpropanoyl)oxy]ethyl})-1,3,5-triazinan-1-yl]ethyl 3-sulfanylpropanoate

Test material form:

liquid: viscous

Specific details on test material used for the study:

SMILES: O=C(OCCn1c(=O)n(c(=O)n(CCOC(=O)CCS)c1=O)CCOC(=O)CCS)CCS
InChI: InChI=1S/C18H27N3O9S3/c22-13(1-10-31)28-7-4-19-16(25)20(5-8-29-14(23)2-11-32)18(27)21(17(19)26)6-9-30-15(24)3-12-33/h31-33H,1-12H2

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.

An overall limited uncertainty was attributed to the negative skin irritating/corrosive prediction generated for TEMPIC, which was then assessed as moderately reliable.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

This QSAR prediction could be used to support the conclusion for no classification.

Conclusions:

TEMPIC 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 moderately reliable. This QSAR prediction indicated a negative skin irritation/corrosion potential of the target TEMPIC 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 Tris[2-(3-mercaptopropionyloxy)-ethyl] isocyanurate (TEMPIC). 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 (313.86°C, EPI Suite) exceeded the property limit of 200°C, thus suggesting a lack of skin irritation or corrosion potential for the target TEMPIC. 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 TEMPIC, which was then assessed as moderately reliable. The skin irritation prediction was thus assessed as adequate for regulatory purposes.