Calcium glycinate (1:2)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

oral toxicity can be considered as a substantial damage to living organisms and human health trough the oral exposure. The aim was to estimate the acute toxicity by oral route of target substance.
Estimation of the acute toxicity by oral 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 REAC, 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Materials and methods

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
II. Multiplication of the target chemical based on the in vivo Rat metabolism simulator.
III. Data collection for the multiplication products (OECD Toolbox database/ECHA CHEM).
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 a Rat metabolism. Thus, the prediction is based on toxicological data of the in vivo Rat metabolism 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 metabolism 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. The acute oral toxicities for the in vivo Rat metabolism products were as follow: 930 mg/kg bdwt for glycine and 2 000 mg/kg bdwt for calcium hydroxide. Considering the worst-case scenario, the acute oral toxicity for the target substance was based on data for calcium hydroxide.

The acute oral toxicity for the source compound was performed according to:
Test guideline: OECD 423
Endpoint: LD50
Test organism: Rat
The read-across prediction of the aquatic toxicity for the target substance was performed based on the “one to one” approach. Considering the worst-case scenario, the acute oral toxicity for the target substance was based on data for calcium hydroxide.

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:

2 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Any other information on results incl. tables

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 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 acute oral toxicity of the calcium glycine (1:2) monohydrate, the read-across hypothesis considers that target compound transforms to two common, non-toxic products. The acute oral toxicities for the metabolites were as follow: 7 930 mg/kg bdwt for glycine and 2 000 mg/kg bdwt for Ca(OH)2. Considering the worst-case

scenario, using experimental data of Ca(OH)2 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 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 (Ca(OH)2) and the target compound (Ca(Gly)xH2O) equals to 13.3%.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity for the target substance is predicted at level LD50 = 2000 mg/kg bdwt.

Executive summary:

The target compound undergoes rat metabolism reaction into its basic products: Gly and Ca(OH)2. Both compounds are not considered as toxic. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. The acute oral toxicities for the metabolites were as follow: 7 930 mg/kg bdwt for glycine and 2 000 mg/kg bdwt for calcium hydroxide. Considering the worst-case scenario, the prediction was based only on the experimental data for Ca(OH)2.