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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
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. Analogue (source compound) search based on selected criteria:
a. analogue dissociates similarly like the target compound (dissociation simulator)
b. analogue has similar transformation products as the target compound (metabolism simulator, 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 undergoes dissociation 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 dissociation products of the target chemical.
The target substance is an organometallic compound containing zinc (Zn) centres, glycine (Gly) and zinc (II) 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 dissociation 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 (ZnSO4) would have similar dissociation products (H2SO4 and Zn(OH)2). However, since there were no data available for the ZnSO4, the prediction was performed based on a transformation analogue search assuming at least 50% similarity between dissociation products of source and target substances. The only one CuSO4 analogue has been found according to the assumed requirements; therefore, it was used as the source compound.
The short-term repeated dose toxicity for the source compound was performed according to:
Test guideline: OECD 412
Endpoint: NOAEL
Test organism: rat
Duration: 28 day
The read-across prediction of the short-term repeated dose toxicity for the target substance was performed based on the “one to one” approach.

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 short-term repeated dose 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 dissociation products of source and target substances (besides glycine) was equal to 50%. CuSO4 analogue has been found as the only one compound with the assumed requirements; therefore, it was used as the source compound.
Besides, the category consistencies, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of Zn(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 (CuSO4) and the target compound Zn(Gly)SO4x2H2O equals to 31.6%

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:
NOAEL
Effect level:
2 mg/m³ air
Basis for effect level:
other: not specific (QSAR)

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
The short-term repeated dose toxicity for the target substance is predicted at level NOAEL = 2.00 mg/m3 air
Executive summary:

The target compound undergoes dissociation reaction into its basic products: Gly, H2SO4 and Zn(OH)2. Due to the glycine is an amino acid, which is not considered as toxic compound, the analogues search was performed assuming 50% structural similarity between dissociation products of source and target substances (besides glycine). The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Copper (II) sulphate would have similar dissociation products (H2SO4 and Cu(OH)2) as well as the experimental data related to the short-term repeated dose toxicity was available. Therefore, the prediction is based only on the CuSO4.