zinc glycyniate

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:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

The fish acute toxicity test provides information on the acute toxicity of chemicals for environmental hazards and risk assessment.
The aim was to estimate the fish acute toxicity of target substance.
2.4.1 Estimation of the biological activity (fish acute toxicity)
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 4.3
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 similar transformation products as the target compound (metabolism simulators, similarity >50%)
c. analogue is structurally similar to the target compound (similarity >40%).
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 undergoes 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 zinc (Zn) 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 Zn(OH)2). Glycine is an amino acid, which is not considered as toxic compound. Zinc (II) sulphate (ZnSO4) would have similar dissociation products (H2SO4 and Zn(OH)2). However, since there were no data available for the ZnSO4, the prediction was performed based on a transformation analogue search assuming at least 50% similarity between dissociation products of source and target substances. Then, the source compound was chosen based on the structural similarity between the target and source compound equal to 40%. Three compounds that met these requirements (and were tested according to the recommended OECD 203 guideline) . According to the worst-case scenario, NiSO4 analogue was used as the source compound. The fish acute toxicity for the source compound was performed according to:
Test guideline: OECD 203
Endpoint: LC50
Test organism: Rasbora sumatrana
Duration: 96h
The read-across prediction of the fish acute toxicity for the target substance was performed based on the approach “one to one”.

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 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 zinc (II) glycine sulphate (VI) dihydrate, the read-across hypothesis considers that source and target compounds have similar transformation products. Based on the Dice measure, the structural similarity between dissociation products of source and target substances (besides glycine) was equal to 50%. Then, the structural similarity between the target and the source compound was assessed and the threshold was at least equal to 40%. Three compounds met these requirements (and were tested according to the recommended OECD 203 guideline). According to the worst-case scenario and the highest structural similarity, NiSO4 analogue was used as the source compound.
Besides, the category consistencies, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of Zn(Gly)SO4x2H2O, the log KOW value is not available. What is more, in case of “one to one” approach, this criterion would be met only if source and target compounds are the same substance. Thus, information that “domain is not defined” is not critical in this situation.
The structural similarity between the source (NiSO4) and the target compound Zn(Gly)SO4x2H2O equals to 42.1%

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.83 mg/L

Nominal / measured:

nominal

Details on results:

The target compound undergoes dissociation reaction into its basic products: Gly, H2SO4 and Zn(OH)2. Due to the glycine is an amino acid, which is not considered as toxic compound, the analogues search was performed assuming 50% structural similarity between dissociation products of source and target substances (besides glycine). Then, the threshold of structural similarity between the target and the source compound was at least equal to 40%. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Nickel (II) sulphate would have similar dissociation products (H2SO4 and Ni(OH)2) as well as the experimental data related to its fish acute toxicity was available. Therefore, the worst-case scenario prediction is based only on the NiSO4.

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

Effect concentration:

0.83 mg/L