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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
Mai 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. Analogue (source compound) search based on selected criteria:
a. analogue hydrolysis similarly like the target compound (hydrolysis simulator (nautral))
b. 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 fact that target compound very easily undergoes a hydrolysis reaction, it is expected that this will be one of the first reactions to which our target chemical is exposed. Thus, the prediction is based on toxicological data of the hydrolysis 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 will break easily and favour hydrolysis 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 hydrolysis products (HSO4- and Zn(OH)2). Therefore, the prediction is based only on the ZnSO4.
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”.

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 oral toxicity of the zinc (II) glycine sulphate (VI) 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 (besides glycine) was at least equal to 50%. Therefore, using experimental data of ZnSO4 for predicting biological activity for the target compound was justified.
Besides, the category consistencies, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of n(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%

Test material

Constituent 1
Chemical structure
Reference substance name:
catena-[(μ-glycine)-diaqua-sulfato-zinc(II)]
EC Number:
805-657-4
Cas Number:
7214-08-6
Molecular formula:
(Zn(SO4)(C2H5NO2) · 2H2O
IUPAC Name:
catena-[(μ-glycine)-diaqua-sulfato-zinc(II)]
Test material form:
solid

Results and discussion

Effect levels
Key result
Dose descriptor:
LD50
Effect level:
1 500 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 =1500 MG/KG

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