Vanadium diascorbate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

Oral toxicity can be considered as a substantial damage to living organisms and human health trough the oral exposure. The aim was to estimate the acute toxicity by oral route of target substance.
Estimation of the acute toxicity by oral route 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

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 >50%)
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 (Acs) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Asc ligands.
The prediction was performed based on a transformation analogue search assuming at least 50% similarity between hydrolysis products of source and target substances. Two compounds that met that requirement were found. The acute oral toxicity for sodium L-ascorbate was measured according to the OECD 401, which is nowadays not recommended, therefore it was not taken into account for the prediction. The 2-ketogluconic acid calcium salt was used as the source compound.
Table 4 Identified analogues
Chemicals/CAS Acute oral toxicity OECD guideline
2-ketogluconic acid calcium salt 5 000 mg/kg bdwt OECD 423
sodium L-ascorbate / 134-03-2 14 100 mg/kg bdwt OECD 401
The acute oral toxicity for the source compound was performed according to:
Test guideline: OECD 423
Endpoint: LD50
Test organism: rat
The read-across prediction of the acute oral toxicity for the target substance was performed based on the approach “one to one”.

Test material

Test material information

Constituent 1

Reference substance name:

Vanadium diascorbate

EC Number:

945-749-2

Cas Number:

1227211-66-6

Molecular formula:

C12H14O13V

IUPAC Name:

Vanadium diascorbate

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Any other information on results incl. tables

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 similar transformation products. Based on the Dice measure, the structural similarity between hydrolyses products of source and target substances was higher than 35%. The experimental data of 2-ketogluconic acid calcium salt 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 2-ketogluconic acid calcium salt, the log KOW value is not available. Thus, information that “domain is not defined” is not critical in this situation.

The structural similarity between the source (2-ketogluconic acid calcium salt and the target compound (vanadyl (IV) diascorbate dihydrate) equals to 38.1%

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity for the target substance is predicted at level LD50 = 5 000 mg/kg bdwt.

Executive summary:

The target compound undergoes a hydrolyses reaction into four products, Figure 4. The analogues search was performed assuming at least 50% 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. The 2-ketogluconic acid calcium salt would have the similar hydrolysis products as well as the experimental data related to its acute oral toxicity was available. Therefore, the prediction is based only on the 2-ketogluconic acid calcium salt.