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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
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.
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.
Principles of method if other than guideline:
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:
- analogue hydrolysed similarly like the target compound (hydrolysis simulator (neutral)),
- analogue has similar transformation products as the target compound (metabolism simulators, similarity >40%),
- analogues are classified as ‘Non-Metals Transition Metals” according to Group of elements (subcategorization).
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 hypothesis that source and target substances have similar toxicological properties like substrates because they hydrolysed to common products.
The target substance is an organometallic compound containing vanadium (IV) centre, and ascorbate (Asc) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Asc ligands.
The target substance hydrolytes into following products:
Zinc D-gluconate (1;2) would have the similar hydrolyses products. The target and source compounds are classified as “Non-Metals Transition Metals” according to Group of elements (subcategorization). The prediction was performed based on a transformation analogue search assuming at least 40% similarity between hydrolysis products of source and target substances. The aquatic toxicity for analogue was measured according to the OECD 202 and that value was taken into account for the prediction.
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 “one to one” approach.
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
22.8 mg/L
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 vanadyl (IV) diascorbate dihydrate, the read-across hypothesis considers that source and target compounds have the similar transformation products and are classified as “Non-Metals Transition Metals” according to Group of elements (subcategorization). Based on the Dice measure, the structural similarity between hydrolyses products of source and target substances was higher than 40%. Using the experimental data of zinc D-gluconate (1;2) 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 vanadyl (IV) diascorbate dihydrate, log KOW value in unavailable thus information that “domain is not defined” is not critical in this situation. The structural similarity between the source (Zinc D-gluconate (1;2)) and the target compound (vanadyl (IV) diascorbate dihydrate) equals to 36.4%
Conclusions:
The aquatic toxicity for the target is predicted at level EC50 = 22.8 mg/L
Executive summary:

The target compound undergoes a hydrolyses reaction into four products, Figure 3. The target and source compounds are classified as “Non-Metals <AND> Transition Metals” according to Group of elements (subcategorization). The analogues search was performed assuming at least 40% structural similarity between hydrolysis products of source and target substances. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Zinc D-gluconate (1;2) would have the similar hydrolysis products as well as the experimental data related to its aquatic toxicity was available. Therefore, the prediction is based only on the zinc D-gluconate (1;2).

Description of key information

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
22.8 mg/L

Additional information