Iron, bis(glycinato-.kappa.N,.kappa.O)-

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

A skin sensitization can be considered as allergic response in animals or humans caused by sensitizer agent.
The aim of the study was to estimate the skin sensitization (human health toxicity testing) of target substance.
Estimation of the biological activity (skin sensitization)
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.

Principles of method if other than guideline:

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 undergoes an autoxidation reaction 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/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 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 iron (Fe) centres, glycine (Gly) 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 Fe(OH)2). Glycine is an amino acid, which is not considered as toxic compound. Iron (II) sulphate would have similar autoxidation products (H2SO4 and Fe(OH)2). Therefore, the prediction is based only on the FeSO4. The skin sensitization for the source compound was performed according to:
Test guideline: OECD 429
Endpoint: skin sensitization
Test organism: Mouse
The read-across prediction of the skin sensitization for the target substance was performed based on the approach “one to one”.

Key result

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

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 iron (II) glycine sulphate (VI) trihydrate, 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 FeSO4 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 Fe(Gly)SO4x3H2O, the log KOW value is not available. Thus, information that “domain is not defined” is not critical in this situation. The structural similarity between the source (FeSO4) and the target compound Fe(Gly)SO4x3H2O equals to 40% .

Interpretation of results:

GHS criteria not met

Conclusions:

The skin sensitization for the target substance is negative - not sensitizing.

Executive summary:

The target compound undergoes an autoxidation reaction into its basic products: Gly, H2SO4 and Fe(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. Iron (II) sulphate would have the same autoxidation products (H2SO4 and Fe(OH)2) as well as the experimental data related to its skin sensitization was available.

Therefore, the prediction is based only on the FeSO4.

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.