titanyl (IV) diascrobate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

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 REAC 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 hydrolyses similarly like the target compound (hydrolysis simulator (neutral))
a. 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 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 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 titanium (IV) centre, and ascorbate (Asc) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Asc ligands.
Three analogues have been found according to the assumed requirements. Two of three compounds had no specific information regarding used OECD guideline. Thus, only one compound was taken into consideration. The aquatic toxicity for analogue was measured according to the OECD 202 and this value was taken into account for the prediction.
Identified analogues that met assumed requirements for aquatic toxicity predictions
Chemicals Aquatic Toxicity to Daphnia Magna [mg/L] OECD guideline
3-O-Ethyl-L-ascorbic acid
CAS 86404-04-8 >78 No information
Sodium L-ascorbate
CAS 134-03-2 >74 OECD 202
2-ketogluconic acid, calcium salt
CAS not given >2.14 No information
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 titanyl (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 hydrolysis products of source and target substances was at least 50%. Therefore, using experimental data of sodium ascorbate 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 TiO(Asc)2 x2H2O, 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 (NaAsc) and the target compound (TiO(Asc)2 x2H2O) equals to 53.7%

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

74 mg/L

Nominal / measured:

nominal

Details on results:

The target compound undergoes a hydrolysis reaction. 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. Sodium L-ascorbate would have similar hydrolysis products as well
as the experimental data related to its aquatic toxicity was available. Therefore, the prediction is based only on the NaAsc.

Validity criteria fulfilled:

yes

Conclusions:

The aquatic toxicity for the target is predicted at level EC50 = 74 mg/L

Description of key information

The aquatic toxicity for the target is predicted at level EC50 = 74 mg/L

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

74 mg/L