Calcium glycinate (1:2)

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Subacute inhalation toxicity (28 days) provides robust data for quantitative inhalation risk assessment.
The aim was to estimate the short-term repeated dose toxicity of target substance.
Estimation of the biological activity (subacute inhalation toxicity (28 days))
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. Simulation of the dissociation 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 issociation 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±). However, due to glycine being not considered as a toxic compound,
it does not contribute significantly to the toxicity. Therefore, the prediction is based only on the Ca(OH)2.
The subacute inhalation toxicity for the source compound was performed according to:
Test guideline: OECD 412
Endpoint: NOAEC
Test organism: rat
Duration: 28 day (6 hours/day)

The read-across prediction of the short-term repeated dose toxicity for the target substance was performed based on the "one to one" approach.

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 acute dermal toxicity of the calcium glycine (1:2) monohydrate, the category members are (bio)transformation products of the target compound. Selected physicochemical properties and toxicological endpoints were analysed to assess the consistency of the category. Due to the chosen scenario, using experimental data of
Ca(OH)2 for predicting biological activity for the target compound was justified.

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

Key result

Dose descriptor:

NOAEL

Effect level:

0.107 mg/L air

Basis for effect level:

other: not specific (QSAR)

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The short-term repeated dose toxicity for the target substance is predicted at level NOAEL = 0,107 mg/l air

Executive summary:

The target compound undergoes a dissociation reaction into its basic products: Ca(OH)2 and Gly±. Thus, the prediction is based solely on the available toxicological data of the dissociation products of the target chemical. Glycine, is an amino acid, which is not considered as toxic compound. Experimental data for short-term repeated dose 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 OECD Guideline 412 and are considered as reliable without restriction and are characterized by a value of NOAEC = 0.107 mg/L air.