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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

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 according to:
i. Group of elements profiler
ii. Chemical elements profiler
b. analogue has the same alerts according to:
i. Acute oral toxicity
ii. Substance type
iii. Toxic hazard classification by Cramer
iv. 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, Lipinski Rule Oasis profiler) expressed in 30-50% structural similarity, as well as consistent alerts according to Acute oral toxicity, Substance type, Toxic hazard classification by Cramer and Toxic hazard classification by Cramer (extended) profilers. Based on the assumed analogue search criteria, three source compounds have been found: CoSO4, ZnSO4 and CuSO4.
The acute dermal toxicity for the source compounds were performed according to:
Test guideline: OECD 402
Endpoint: LD50
Test organism: rat
The read-across prediction of the acute toxicity by dermal route for 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). Compounds used as
source compounds for prediction are presented in Table.
Table
Source compounds for the acute toxicity by dermal route prediction.
No. CAS Name LD50 Test guideline
1. 10124-43-3 cobalt (II) sulphate 2000 mg/kg OECD 402
2. 77733-02-0 zinc (II) sulphate 2000 mg/kg OECD 402
3. 7758-98-7 copper (II) sulfate 2000 mg/kg OECD 402

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.10 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 dermal toxicity of the iron (II) glycine sulphate (VI) trihydrate, the 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 test organism is exposed to compounds, which have the same structural features as the
target compound according to profilers: Groups of elements (Transition etalsNonmetals),
Chemical elements (Group 16 – Oxygen OGroup 16 – Sulfur S) and Lipinski Rule Oasis (Bioavailable). All category members exhibit consistent alerts according to Acute oral toxicity, 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 (CoSO4 and ZnSO4)
and the target compound Fe(Gly)SO4x3H2O is equals to 47.1%, while the structural similarity
between the source CuSO4 and the target compound Fe(Gly)SO4x3H2O is equals to 35.3%.

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

Key result

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Clinical signs:

other:

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The category members have the same toxicological properties due to common underlying
mechanism after administration because of their high structural similarity. Moreover, there is
not observed quantitative diversification in toxic response for acute dermal toxicity (OECD
Guideline 402) between source compounds – all of them are characterized with the same value
of LD50 >2E+03 mg/kg, what means that are classified according to GHS criteria to Category
5 – warning – “may be harmful in contact with skin”. All category members exhibit
qualitatively and quantitatively the same adverse effects in acute dermal toxicity studies. 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 402 and are considered as reliable without (CoSO4, CuSO4) and with (ZnSO4)
restriction, respectively.