Calcium glycinate (1:2)

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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 4.37
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 (Appendix 1.2B).
II. Multiplication of the target chemical based on the autoxidation simulator.
III. Data collection for the multiplication products (OECD Toolbox database/REACH Skin sensitization database).
IV. Toxicity prediction for the target substance based on the worst-case scenario
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 manganese (Ca) 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 and Ca(OH)2). Glycine is an amino acid which is not considered as toxic compound. Calcium hydroxide is an inorganic compound used in many applications, including food preparation, then also not considered as toxic. In the OECD QSAR Toolbox database, the experimental data related to skin sensitization were available only for the glycine (negative).

Skin sensitization for calcium hydroxide was negative as well (according to the data found in Safety Data Sheet (SDS)).
The skin sensitization for the source compound was performed according to:
Test guideline: OECD 429
Endpoint: skin sensitization (EC3)
Test organism: mouse cell LLNA
The read-across prediction of the skin sensitization for the target substance was performed based on the approach “one to one”, on data available for glycine.

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.9 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 QSAR

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 calcium glycine (1:2) monohydrate, the read-across hypothesis considers that target compound transforms to two common, non-toxic products. The skin sensitization for the transformation products were as follow: negative for glycine and negative for calcium hydroxide. Considering the higher level of structure similarity between target and glycine, than Ca(OH)2, using experimental data of glycine for was justified.

Besides, the category consistency, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of Ca(Gly)xH2O, 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 (glycine) and the target compound (Ca(Gly)xH2O)

equals to 35.3% .

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 autooxidation reaction into its basic products: Gly and Ca(OH)2. Both compounds are not considered as toxic. The skin sensitization prediction was performed based on the experimental data included in the OECD QSAR Toolbox. The endpoint values for the autooxidation products were as follow: negative for glycine and negative for calcium hydroxide. Considering the higher level of structure similarity between target and glycine, than Ca(OH)2, the prediction was based only on the experimental data for glycine.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

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.