Iron, bis(glycinato-.kappa.N,.kappa.O)-

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 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.

Data source

Reference

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Principles of method if other than guideline:

Applied tool:
The OECD QSAR Toolbox, version 4.3
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 transformation products as the target compound (metabolism simulators).
III. Data collection for the analogues (OECD Toolbox database/ECHA CHEM).
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 very easily undergoes a 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 iron (Fe) 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 dissociation of the substance into its basic products (Gly, H2SO4 and Fe(OH)2). Glycine is an amino acid, which is not considered as toxic compound. Iron (II) sulphate would have similar dissociation products (H2SO4 and Fe(OH)2). Therefore, the prediction is based only on the FeSO4.
The acute oral toxicity for the source compound was performed according to:
Test guideline: OECD 401
Endpoint: LD50
Test organism: Rat
The read-across prediction of the acute oral toxicity for the target substance was performed based on the approach “one to one”.

Test material

Test material information

Constituent 1

Reference substance name:

bis(λ⁴-iron(2+)) tetrakis(2-aminoacetate)

EC Number:

606-444-7

Cas Number:

20150-34-9

Molecular formula:

C4H8FeN2O4

IUPAC Name:

bis(λ⁴-iron(2+)) tetrakis(2-aminoacetate)

Test material form:

solid

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

965 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 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 iron (II) glycine sulphate (VI) tihydrate, the read-across hypothesis considers that source and target compounds have the same transformation products. Based on the Dice measure, the structural similarity between dissociation products of source and target substances (besides glycine) was equal to 100%. Therefore, using experimental data of FeSO4 for predicting biological activity

for the target compound was justified.

Besides, the category consistencies, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of Fe(Gly)SO4x3H2O, 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 (FeSO4) and the target compound Fe(Gly)SO4x3H2O equals to 40% .

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 = 965 mg/kg bdwt.

Executive summary:

The target compound undergoes a dissociation reaction into its basic products: Gly, H2SO4 and Fe(OH)2. Due to the glycine is an amino acid, which is not considered as toxic compound, the analogues search was performed assuming 100% (“exact match”) structural similarity between dissociation products of source and target substances (besides glycine).

The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Iron (II) sulphate would have the same dissociation products (H2SO4 and Fe(OH)2) as well as the experimental data related to its acute oral toxicity was available.

Therefore, the prediction is based only on the FeSO4.