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

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)

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:

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 has the same structural features as the target compound according to:
i. Group of elements profiler
ii. Chemical of elements profiler
iii. Substance type profiler
b. analogue has the same alerts according to:
i. OECD HPV Chemical Categories
ii. Protein binding by OASIS
iii. Substance type profiler
iv. Toxic hazard classification by Cramer
v. Toxic hazard classification by Cramer (extended)
III. Data collection for the analogues (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 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 the similarity according to the considered structural profilers (Group of elements profiler, Chemical of elements profiler,
Substance type profiler) expressed in 47,1% structural similarity, as well as consistent alerts acco
rding to OECD HPV Chemical Categories, Protein binding by OASIS, Substance type,
Toxic hazard classification by Cramer and Toxic hazard classification by Cramer (extended) profilers.
Based on the assumed analogue search criteria, two source compounds have been
found: MnSO4 and NiSO4.
The acute inhalation toxicity for the source compounds were performed according to:
Test guideline: OECD 403
Endpoint: LC50
Test organism: rat
Duration: 48h
The read-across prediction of the acute inhalation toxicity the target substance was performed based on the many to one approach and the worst-case scenario (when multiple values are
available, the minimal value is taken in prediction calculations).
Table . Source compounds for the acute inhalation toxicity predictions.
No. CAS Name LC50 Test guideline
1. 7785-87 manganese (II) sulphate 2.48 mg/L air OECD 403
2. 7786-81-4 nickel (III) sulphate 4.45 mg/L air OECD 403

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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 compoonds (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 iron (II) glycine
sulphate (VI) trihydrate, 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:
Groups of elements (Transition metalsNon-metals), Chemical elements (Group 16 Oxygen
OGroup 16 Sulfur S) and Lipinski Rule Oasis (Bioavailable). Source compounds exhibit structural similarity to the target compound in the range [40-50%]. The target compound and the source compounds exhibit similar toxicity effects due to the structural similarity. All category members exhibit consistent alerts according to OECD HPV Chemical Categories, Protein binding by OASIS, Substance type, Toxic hazard classification by Cramer and Toxic hazard classification by Cramer (extended) profilers. Besides, the category consistencies, the boundaries of the applicability domain are verified by the critical value of the bioconcentration factor (BCF). In case of Fe(Gly)SO4x3H2O the BCF is in the range of descriptor. The structural similarity between the source (MnSO4 and NiSO4) and the target compound Fe(Gly)SO4x3H2O is equals to 47.1%.

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:

LC50

Effect level:

2.48 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 = 2.48 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. Due to the different transition metals, the strength of toxic effects may vary slightly, however, according to the GHS criteria, when LC50 between 1.0 and less than 5.0 (mg/L) substance belong to the Category 4 - warning - harmful if inhaled. Thus, both category members belong to the same category.
Nevertheless, the prediction for the target compound is based on the worst-case scenario - the highest observed toxicity among the category members. 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.