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

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)

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 predi
ctions 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 a
ction and observed or simulated metabolites
II. Analogue (source compound) search based on selected criteria:
a. analogue (bio)transforms similarly like the target compound (dissociation simulator)
b. analogue has the same structural features according to:
i. Group of elements profiler
ii. Chemical elements profiler
c. analogue has the same alerts according to:
i. OECD HPV Chemical Categories
ii. Substance type profiler
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 1
Toxicity prediction for the target substance:
This read-across is based on the fact that target and source compound very easily undergo a rapid
dissociation reaction, it is expected that this will be one of the first reactions to which our
target and source chemicals are exposed. As a result, all category members dissociate into transition
metal ions and sulphate ions. The target compound - iron (II) glycine sulphate (VI)
trihydrate - dissociates into iron (II) ion, sulphate ion and glycine, however, due to glycine is amino a
cid, it is not considered as a toxic compound. Hydrogen ions resulted from the degree
of the target compound hydration are neglected. Based on the assumed analogue search criteria, one
source compound has been found: CuSO4.
The subacute inhalation toxicity for the source compound was evaluated according to:
Test guideline: OECD 412
Endpoint: NOAEL
Test organism: rat
Duration: 28 day
The read-across prediction of the of the subacute inhalation toxicity for the target substance was
performed based on one to one approach.

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 consistence of the group of source compounds (called category in OECD Toolbol 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 short-term repeated dose toxicity of the iron (II)
glycine sulphate (VI) trihydrate, the read-across hypothesis considers that source and target
compounds have the same (bio)transformation products. This read-across is based on the fact that target and source compounds very easily undergo a rapid dissociation reaction, it is expected that this will be one of the first reactions to which our target and source chemicals are e
xposed. As a result, all category members dissociate into transition metal ions and sulphate
ions. The target compound - iron (II) glycine sulphate (VI) trihydrate - dissociates into iron (II) ion,
sulphate ion and glycine, however, due to glycine is amino acid, it is not considered as a
toxic compound. Hydrogen ions resulted from the degree of the target compound hydration are neglected. All category members exhibit the same/similar results according to the structure
similarity profilers (Chemical elements, Groups of elements, Lipinski Rule Oasis). Both category
members exhibit consistent results according to Substance type profiler. Thus, the
prediction for the target compound is based on the structural similarity of category members dissociati on products.
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 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:

NOAEL

Effect level:

2 mg/m³ 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 = 2.00 mg/m3 air

Executive summary:

The target compound undergoes a dissociation reaction into its basic products: Gly, H2SO4 and Fe(OH)2. The transformation products of target and source compounds exhibit physicochemical and structural similarity, undergo dissociation reaction. All category members exhibit the same/similar results according to the structure similarity profilers (Chemical elements, Groups of elements, Lipinski Rule Oasis). Therefore, the target and source compounds have similar toxicological
properties and cause similar effects. Thus, the prediction for the target compound in based on the structural similarity of category members dissociation products. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Experimental data gathered for source compound was obtained with recommended OECD Guideline 412 and assessed as reliable without restrictions.