titanyl (IV) diascrobate

Endpoint summary

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:

The computational simulation was performed based on the read-across approach. The readacross is one of the so-called alternative test methods recommended by REACH, where the predictions are based on the experimental data available for the most similar compounds. The predictions were performed according to the Read-Across Assessment Framework (RAAF), which assumes six different risk assessment scenarios of chemical compounds.
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 has the same structural features as the target compound (protein binding alerts based on the Protein Binding by OECD profiler and classification
as ‘Lactones’ according to the Protein Binding Potency h-CLAT)
b. analogue is structurally similar to the target compound (similarity >50%).
III. Data collection for the analogues (OECD Toolbox database/ECHA CHEM).
IV. Toxicity prediction for the target substance
V. Category consistency check in order to assess the quality of the prediction
Applied scenario:
Scenario 2
Toxicity prediction for the target substance:
This read-across is based on the fact that the organism is not exposed to common compounds but rather, as a result of similarity, to chemicals which have similar (eco)toxicological and fate properties.
The target substance is an organometallic compound containing titanium (IV) centres, ascorbate (Asc) ligands. The metallic centres of the substance are linked by oxygen
coordination bonds of the Asc ligands.
The target and source chemicals are classified as “Lactones” according to Protein binding by h-CLAT Categories and have the similar protein binding alert responsible for the toxic effect based on the Protein binding by OECD profiler. Moreover, analogue is structurally similar to the target compound in more than 50%. One compound that met these
requirements was found (sodium L-ascorbate, CAS 134-03-2).
The skin sensitization for the source compound was performed according to:
Test guideline: OECD 429
Endpoint: skin sensitization
Test organism: mouse LLNA
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 applicabilitydomain. 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 titanyl (IV) diascorbate dihydrate, the read-across hypothesis considers that source and target
compounds are classified as “Lactones” according to Protein binding by h-CLAT Categories and have the similar protein binding alert responsible for the toxic effect based on the Protein binding by OECD profiler. Moreover, based on the Dice measure analogue is structurally similar to the target compound in 53.7%.
Besides, the category consistency, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of titanyl (IV) diascorbate dihydrate, 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 (sodium L-ascorbate) and the target compound (titanyl (IV) diascorbate dihydrate) equals to 53.7 %.

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 source and target compounds are classified as “Lactones” according to Protein binding by h-CLAT Categories and have the similar protein binding alert responsible for the toxic effect based on the Protein binding by OECD profiler. Moreover, analogue is structurally similar to the target compound in more than 50%. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. One chemical would meet the requirements related to their profile and structure as well as the experimental data related to their skin sensitization. Therefore, the prediction is based on sodium L-ascorbate.

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.