Calcium glycinate (1:2)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Justification for type of information:

Acute dermal toxicity refers to those adverse effects occurring following a single dermal (skin) exposure to the substance within 24 h.
The aim was to estimate the acute toxicity by dermal route of target substance.
2.5.1 Estimation of the biological activity (acute toxicity by dermal route)
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 4.4
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 1.5B).
II. Simulation of the (bio)transformation process (in vivo rat simulator) determination of source compounds.
III. Data collection for the transformation products (OECD Toolbox database).
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 dissociation 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 dissociation products of the target chemical.
The target substance is an organometallic compound containing calcium (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 break easily and favour rapid dissociation of the substance into its basic products (Ca(OH)2, Gly±). Glycine is an amino acid which is not considered as toxic compound.
Therefore, the prediction is based only on the Ca(OH)2.
The acute dermal toxicity for the source compound was performed according to:
Test guideline: EU Method B.3 (Acute Toxicity (Dermal))
Endpoint: LD50
Duration: 24h
Test organism: rabbit
The read-across prediction of the acute dermal toxicity for the target substance was performed based on the approach "one to one".

Data source

Reference

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

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.10 In a specific case of read-across, 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 should 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 gene mutation of the calcium glycine (1:2) monohydrate, the category members are dissociation products of the target compound. Selected physicochemical properties and toxicological endpoint were analysed to assess the consistency of the category. Additionally, for the target and source compounds no structural alerts for endpoint related profiles were found. Due to the chosen scenario, using experimental data of
Ca(OH)2 for predicting biological activity for the target compound was justified.

GLP compliance:

no

Remarks:

QSAR

Test material

Test material information

Constituent 1

Reference substance name:

Calcium glycinate (1:2)

EC Number:

252-809-5

EC Name:

Calcium glycinate (1:2)

Cas Number:

35947-07-0

Molecular formula:

(C4H10N2O5Ca)n)

IUPAC Name:

catena (q3-glycinato-(q2-glycinato)-aqua-calcium)

Test material form:

solid: crystalline

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Clinical signs:

other:

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute dermal toxicity for the target substance is predicted at level LD50> 2500 mg/kg bdwt

Executive summary:

The target compound undergoes a (bio)transformation into its basic products: Ca(OH)2 and Gly±. Thus, the prediction is based solely on the available toxicological data of the transformation products of the target chemical. Glycine, is an amino acid, which is not considered as toxic compound. The acute dermal toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Experimental data for acute dermal toxicity study are available for calcium (II) hydroxide, therefore the toxicity was predicted from the source substance (not from structural analogues of source substance).
Experimental data gathered for source substance were obtained with recommended EU Method B.3 and are characterized by a value of LD50 > 2500mg/kg.