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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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 perfo
rmed 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 (bio)transforms similarly like the target compound (dissociation simulator)
b. analogue has the same structural features as the target compound according to:
i. Groups of elements profiler
ii. Chemical elements profiler
iii. Organic functional groups, Norbert Haider (checkmol) profiler
c. analogue has the same alerts according to:
i. Acute Aquatic Toxicity Classification by Verhaar (Modified)
ii. Acute Aquatic Toxicity MOA by OASIS
iii. Aquatic Toxicity Classification by ECOSAR.
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 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 exposed. As a result, it is considered that all category members d
issociate 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 g
lycine is amino acid, 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, two source compounds have been found: MnSO4 and NiSO4.
The fish acute toxicity for the source compounds were performed according to:
Test guideline: OECD 203
Endpoint: LC50
Test organism: Oncorhynchus mykiss for MnSO4 and Rasbora sumatrana for NiSO4
Duration: 96h
The read-across prediction of the fish acute toxicity 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 prediction of the fish acute toxicity.
No. CAS Name LC50 Test guideline
1. 7785-87-7 manganese (III) sulphate 14.5 mg/L OECD 203
2. 7786-81-4 nickle (III) sulphate 0.83 mg/L OECD 203

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 fish acute toxicity of the iron (II) glycine
sulphate (VI) trihydrate, the read-across hypothesis considers that source and target compounds
have similar toxicological properties due to common underlying mechanism after
administration. All category members undergo dissociation reaction and exhibit the
same/similar results (i.e. transition metals, sulfuric acid derivative) according to the structure
similarity profilers (Groups of elements, Chemical elements, Lipinski Rule Oasis). All category
members have no endpoint specific alerts according to Acute Aquatic Toxicity Classification by Verhaar (Modified), Acute Aquatic Toxicity MOA by OASIS and Aquatic Toxicity
Classification by ECOSAR. The structural similarity between the source (MnSO4 and NiSO4)
and the target compounds Fe(Gly)SO4x3H2O is equals to 47.1%.
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 .

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.83 mg/L

Nominal / measured:

nominal

Details on results:

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 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 (MnSO4 and NiSO4).
All category members exhibit the same adverse effects. However, due to the diversification of
the strength in toxic responses between category members, the worst-case scenario was
assumed in the predictions for the target compound. Experimental data gathered for source
substances were obtained with recommended OECD Guideline 203 and are considered as
reliable with/without restriction, respectively. Experimental data for fish acute toxicity, i.e.
LC50 is between 0.83 mg/l and 14.5 mg/l, (test OECD 203). According to CLP classifications
when those toxicity values are below 1mg/l, the substance is assigned to category 1 – the most
severe hazard to aquatic environment (GHS hazard statement), while when those toxicity values
are in range (10 – 100 mg/l), the substance is assigned to category 3 – harmful to aquatic
environment (GHS hazard statement). Thus, considering that the prediction for the target
compound is based on the worst-case scenario – the toxic effect of target substance can be
classified as very toxic to aquatic environment (Category I).

Validity criteria fulfilled:

yes

Conclusions:

The fish acute toxicity for the target substance is predicted at level LC50 = 0,83 mg/L.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

EC50

Effect concentration:

0.83 mg/L

Additional information

The fish acute toxicity for the target substance is predicted at level LC50 = 0.83 mg/L.