Calcium glycinate (1:2)

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Justification for type of information:

Acute inhalation toxicity is the total of adverse effect caused by substance following the single uninterrupted exposure by inhalation over a short period of time to a substance capable of being inhaled.
The aim was to estimate the acute toxicity by inhalation of target substance.
2.4.1 Estimation of the biological activity (acute toxicity by inhalation)
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
II. Analogue (source compound) search based on selected criteria:
a. analogue dissociates similarly like the target compound (dissociation simulator)
b. analogue has the same structural features as the target compound according to:
i. Substance type profiler
ii. Chemical elements profiler (subcategorization)
iii. Structure similarity (subcategorization)
III. Data collection for the analogues (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 2
Toxicity prediction for the target substance:
This read-across is based on the fact that the target and the source compounds are similar in terms of their physicochemical, (eco)toxicological and fate properties. The target compound and the source compounds exhibit similar toxicity effects due to their structural similarity.
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 target compound and the source compounds exhibit similar toxicity effects due to the structural similarity. The prediction was performed basing on the source compound, which was found similar with the target compound according to similarities within
the substance types (dissociating chemicals, organic, mono constituents), chemical elements and overall calculated structural similarity of their structures. The overall structural similarity to the target compound is in range of 50%. Calcium diacetate is used as the source compound to predict the screening reproductive toxicity.
The acute inhalation toxicity for the source compound was performed according to:
Test guideline: OECD 403
Endpoint: LC50
Test organism: rat
Duration: 4h
The read-across prediction of the acute inhalation toxicity the target substance was performed based on the "one to one" approach. Compound ussed as soure compound for prediction is presented in Table 4.
Table 4 Source compounds for acute toxicity by inhalation
No. CAS Name LC50 Test guideline
1. 62-54-4 calcium diacetate 5.6 mg/L air OECD 403

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. 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 acute inhalation toxicity of the calcium glycine (1:2) monohydrate, the read-across hypothesis considers that source and target compounds are similar in terms of their physicochemical, (eco)toxicological and fate properties.
The prediction for the target compound is based on the structural similarity of category members. All category members have the same structural features according to the structure similarity profilers: Substance type (Dissociating chemicalOrganicMono constituent), Chemical elements (Group 16 - Oxygen OGroup 14 - Carbon CGroup 15 - Nitrogen NGroup 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra).
Source compounds exhibit structural similarity to the target compound in the range [50-60%].
Additionally, all category members exhibit similar values of selected calculated
physicochemical parameters. The target compound and the source compounds exhibit similar toxicity effects due to the structural similarity.
Moreover, the category consistencies, the boundaries of the applicability domain are verified by the value of the bioconcentration factor (BCF). In case of calcium glycine (1:2) monohydrate, the BCF is in the range of descriptor. The structural similarity between the source (calcium diacetate) and target (calcium glycine (1:2) monohydrate) is 50% .

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:

LC50

Effect level:

5.6 mg/L air

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute inhalation toxicity for the target substance is predicted at level LC50 = 5,6 mg/L air.

Executive summary:

The category members have similar toxicological properties due to common underlying mechanism after administration because of their high structural similarity. The prediction for the target compound in based on the "one-to-one" approach. The target compound has the same structural features as source compound according to the substance type and chemical elements.
The structural similarity between the source (calcium diacetate) and target (calcium glycine (1:2) monohydrate) is 50%. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Experimental data gathered for source substances were obtained with recommended OECD Guideline 403 and are considered as reliable without restriction and is characterized by a value of LC50 = 5.6 mg/L air.