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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
in silico prediction
Type of information:
(Q)SAR
Adequacy of study:
supporting 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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) version 2.6.13

2. MODEL (incl. version number)
Toxtree v2.6.13

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES = CCCCCCCCCCCCCCCCOC1OC(CO)C(O)C(O)C1O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: skin sensitisation
- Unambiguous algorithm: : identification of structural alerts for aromatic nucleophilic substitution (SNAr), Schiff base formation (SB), Michael-type addition (MA), aliphatic nucleophilic substitution (SN2) and acylation (Ac) (potential mechanisms of action regarded as important for determining a chemical’s skin sensitising potential)

The SMARTS rules aim to identify potential electrophilic fragments and therefore identify a potential hazard associated with a compound, it is up to the user to apply issues relating to bioavailability etc.
The algorithm then attempts to match each of the input SMILES strings against each of the SMARTS patterns. If a chemical matches one or more of the SMARTS patterns within each mechanism then it is assigned to that mechanism. If a chemical matches multiple SMARTS patterns from more than a single mechanism then it is assigned to each of the mechanisms which it matches. A chemical is only assigned to the category ‘non-sensitiser’ if it fails to match any of the SMARTS patterns in any of the mechanistic categories.

Reference
Enoch SJ, Madden JC, Cronin MT, Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach, SAR QSAR Environ Res. 2008;19(5-6):555-78


5. APPLICABILITY DOMAIN
The training set contained a recently published 210 chemical LLNA assay database to derive a set of SMARTS patterns capable of identifying potential mechanisms of action. Having defined the initial SMARTS patterns, a second recently published series of 44 LLNA assay results with mechanisms of action assigned to them was used to validate the rules.

6. ADEQUACY OF THE RESULT
The Toxtree estimation revealed that there are no structural fragments associated with skin sensitisation reactivity domains, thus, based on structure the substance is
considered not to be a sensitizer.

Data source

Reference
Reference Type:
other: QSAR: Expert statement
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
QSAR prediction with Toxtree decision tree approach.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
C16-18 alkyl-D-glucoside
IUPAC Name:
C16-18 alkyl-D-glucoside
Constituent 2
Chemical structure
Reference substance name:
C16-18-alkyl diglucoside
IUPAC Name:
C16-18-alkyl diglucoside
Constituent 3
Chemical structure
Reference substance name:
C16-18-alkyl triglucoside
IUPAC Name:
C16-18-alkyl triglucoside
Test material form:
solid: particulate/powder

Results and discussion

Any other information on results incl. tables

Results

No skin sensitisation reactivity domains alerts identified. = YES

Alert for SN2 identified. = NO

Alert for Michael Acceptor identified. = NO

Alert for Acyl Transfer agent identified. = NO

Alert for SNAr Identified. = NO

Alert for Schiff base formation identified. = NO

 

No skin sensitisation reactivity domains alerts identified.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on a reliable prediction performed with the Toxtree software, D-Glucose reaction products with alcohols C16 -C18 is not considered to be a skin sensitizer.
Executive summary:

The sensitising potential of D-Glucose reaction products with alcohols C16 -C18 was estimated using the Toxtree decision tree

approach. This QSAR software predicts the sensitising potential via skin sensitisation reactivity domains.

No structural alert was found for D-Glucose reaction products with alcohols C16 -C18. The test item is therefore considered to be

a non-sensitizer.