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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vitro
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2019
Reliability:
1 (reliable without restriction)
Justification for type of information:
Applied tool:
The OECD QSAR Toolbox, version 4.3
Procedure of analysis:
I. Profiling of the target substance in order to retrieve relevant information related to mechanism of action and observed or simulated metabolites
II. Analogue (source compound) search based on selected criteria:
a. analogue autoxidates similarly like the target compound (autoxidation simulator)
b. analogue has the same metabolites as the target compound.
III. Data collection for the analogues (OECD Toolbox database/REACH Skin sensitisation database (normalised).
IV. Toxicity prediction for the target substance
V. Category consistency check in order to assess the quality of the prediction
Applied scenario:
Scenario 1
Toxicity prediction for the target substance:
This read-across is based on the fact that target compound undergoes an autoxidation reaction,
it is expected that this will be one of the first reactions to which our target chemical is exposed. Thus, the prediction is based on toxicological data of the autoxidation products of the target chemical.
The target substance is an organometallic compound containing zinc (Zn) centres, glycine (Gly) and zinc (II) sulphate (ZnSO4) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Gly ligands.
The weak bonds between metallic centres and the oxygen atoms in the compound structure will break easily and favour autoxidation of the substance into its basic products: (Gly, H2SO4 and Zn(OH)2). Glycine is an amino acid, which is not considered as toxic compound. Zinc (II) sulphate would have similar autoxidation products (H2SO4 and Zn(OH)2). Therefore, the prediction is based only on the ZnSO4.
The skin sensitization for the source compound was performed according to:
Test guideline: OECD 406
Endpoint: skin sensitization
Test organism: Guinea pig
The read-across prediction of the skin sensitization for the target substance was performed
based on the approach “one to one”.
Principles of method if other than guideline:
In order to meet regulatory needs, reliability of the predicted results should be assessed. In case of classic quantitative structure-activity relationships (QSAR) modelling, this idea can be realised by analysing, whether the predicted value is located within so-called applicability domain. The applicability domain is a theoretical region, defined by the range of toxicity values and structural descriptors for the training compounds, where the predictions may be considered as realistic ones. In a specific case of read-across, the assessment is performed based on the assessment of degree of similarity between the source and target compounds (in %). Moreover, the internal consistency of the group of source compounds (called „category” in OECD Toolbox nomenclature, independently which approach: analogue approach or category approach is used). The category consistency check could be based on the parameters describing the structural similarity and/or properties as well as mechanistic similarity of the tested compounds. For example, all members of the category (analogues as well as target substance) need to have the same functional groups and endpoint specific alerts.
In the case of read-across-based prediction of the skin sensitization of the zinc (II) glycine sulphate (VI) dihydrate, the read-across hypothesis considers that source and target compounds have the same transformation products. Based on the Dice measure, the structural similarity between autoxidation products of source and target substances (besides glycine) was equal to 100%. Therefore, using experimental data of ZnSO4 for predicting biological activity for the target compound was justified.
Besides, the category consistency, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of Zn(Gly)SO4x2H2O, the log KOW value is not available. What is more, in case of “one to one” approach, this criterion would be met only if source and target compounds are the same substance. Thus, information that “domain is not defined” is not critical in this situation.
The structural similarity between the source (ZnSO4) and the target compound Zn(Gly)SO4x2H2O equals to 42.1%
GLP compliance:
yes (incl. QA statement)
Key result
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The skin sensitization for the target substance is negative.
Executive summary:

The target compound undergoes an autoxidation reaction into its basic products: Gly, H2SO4 and Zn(OH)2. Due to the glycine is an amino acid, which is not considered as toxic compound, the analogues search was performed assuming 100% (“exact match”) structural similarity between autoxidation products of source and target substances (besides glycine). The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Zinc (II) sulphate would have the same autoxidation products (H2SO4 and Zn(OH)2) as well as the experimental data related to its skin sensitization was available.

Therefore, the prediction is based only on the ZnSO4.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitization for the target substance is negative.