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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2019
Reliability:
1 (reliable without restriction)
Justification for type of information:
Aquatic toxicity can be considered as a substantial damage to living organisms and human health trough the aquatic exposure.
The aim of the study was to estimate the aquatic toxicity (short-term toxicity testing on invertebrates) of target substance.
2.1.1 Estimation of the biological activity (aquatic toxicity, short-term toxicity testing on invertebrates)
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 the same metabolites as the target compound.
III. Data collection for the analogues (OECD Toolbox database/ECOTOX).
IV. Toxicity prediction for the target substance based on the worst-case scenario
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 a dissociation reaction, it is expected that this will be one of the first reactions to which our target chemical is exposed. As it was described within the Appendix A, the target substance dissociates completely into Zn2+, SO42- and Gly±. 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) and zinc sulphate (ZnSO4) 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 break easily and favour rapid 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 would have similar dissociation products (H2SO4 and Zn(OH)2). Therefore, the prediction is based only on the ZnSO4. The aquatic toxicity for the source compound was performed according to:
Test guideline: OECD 202
Endpoint: EC50
Test organism: Daphnia Magna
Duration: 48h
The read-across prediction of the aquatic 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 aquatic toxicity of the zinc (II) glycine sulphate (VI) dihydrate, the read-across hypothesis considers that source and target compounds have the same transformation products. Based on the Dice measure, the structural similarity between dissociation products of source and target substances (besides glycine) was equal to 100%. Therefore, using experimental data of ZnSO4 for predicting biological activity for the target compound was justified.
Besides, the category consistency, 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 (ZnSO4) and the target compound (Zn(Gly)SO4x2H2O) equals to 42.1%
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
2.1 mg/L
Nominal / measured:
nominal
Details on results:
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 aquatic toxicity of the zinc (II) glycine sulphate (VI) dihydrate, the read-across hypothesis considers that source and target compounds have the same transformation products. Based on the Dice measure, the structural similarity between dissociation products of source and target substances (besides glycine) was equal to 100%. Therefore, using experimental data of ZnSO4 for predicting biological activity for the target compound was justified.
Besides, the category consistency, 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 (ZnSO4) and the target compound (Zn(Gly)SO4x2H2O) equals to 42.1%
Validity criteria fulfilled:
yes
Conclusions:
The aquatic toxicity for the target is predicted at level EC50 = 2.10 mg/L

Description of key information

The aquatic toxicity for the target is predicted at level EC50 = 2.10 mg/L

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
2.1 mg/L

Additional information