titanyl (IV) diascrobate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

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. Category (source compounds) search based on selected criteria:
a. analogue is structurally similar to the target compound (similarity >30%)
b. analogue has the same alert according to the Acute Oral Toxicity profiler
c. analogue has the same alert “High level” according to the Cramer profile.
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 2
Toxicity prediction for the target substance:
This read-across is based on the fact that the organism is not exposed to common compounds but rather, as a result of similarity, to chemicals which have similar (eco)toxicological and fate properties.
The target substance is an organometallic compound containing titanium (IV) centres, ascorbate (Asc) ligands. The metallic centres of the substance are linked by oxygen
coordination bonds of the Asc ligands. The target and source chemicals are classified as “High (Class III)” according to the Toxic hazard classification by Cramer profiler and they are not categorized according to the Acute Oral Toxicity profiler. Also, analogues are structurally similar to the target compound in more than 30%. Two compounds that met these requirements were found, but only one was tested with the recommended OECD 402 guideline (D-gluconic acid, CAS 526-95-4) and was chosen as the source compound and taken into account for the prediction.
Table. Identified analogues that met the assumed requirements for acute toxicity by dermal route predictions
Chemicals Acute Toxicity by dermal route [mg/kg bdwt] OECD guideline
Sodium erythorbate
CAS 6381-77-7 2 000 No information
D-gluconic acid
CAS 526-95-4 2 000 OECD 402
The acute dermal toxicity for the source compound was performed according to:
Test guideline: OECD 402
Endpoint: LD50
Test organism: rat
The read-across prediction of the acute dermal toxicity for the target substance was performed based on the approach “one to one”.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

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 acute toxicity by dermal route of the titanyl (IV) diascorbate dihydrate, the read-across hypothesis considers that source and target compounds are classified as “High (Class III)” according to the Toxic hazard classification by
Cramer profiler and they are not categorized according to the Acute Oral Toxicity profiler.
Also, analogues are structurally similar to the target compound in more than 30%.
Besides, the category consistency, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of titanyl (IV) diascorbate dihydrate, 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 (D-gluconic acid) and the target compound (titanyl (IV) diascorbate dihydrate) equals to 34,1 %.

GLP compliance:

no

Remarks:

QSAR

Test material

Test material information

Constituent 1

Reference substance name:

(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2,5-dihydrofuran-2-one titanium

EC Number:

814-615-4

Cas Number:

122958-50-3

Molecular formula:

TiO(Asc)2 x2 H2O

IUPAC Name:

(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2,5-dihydrofuran-2-one titanium

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Clinical signs:

other:

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute dermal toxicity for the target substance is predicted at level LD50 = 2000 mg/kg bdwt

Executive summary:

The source and target compounds are classified as “High (Class III)” according to the Toxic hazard classification by Cramer profiler. Also, analogues are structurally similar to the target compound in more than 30%. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Two chemicals met the assumed requirements, but due to the availability of experimental data obtained with the recommended OECD 402 guideline related to the acute toxicity by dermal route and the worst-case scenario, D-gluconic acid was chosen as the source compound.