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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
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 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. Category (source compounds) search based on selected criteria:
a. analogues are aliphatic amines according to US-EPA New Chemical Categories
b. analogues are structurally similar to the target compound (similarity >20%)
c. analogues have 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
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 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 target and source chemicals are classified as “Aliphatic amines” according to US-EPA New Chemical Categories and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. Moreover, analogues are structurally similar to the target compound in more than 20%. The acute dermal toxicity for analogue was measured according to the OECD 402. The prediction was based on the monoethanolamine thioglycolate. 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 dermal toxicity of the zinc (II) glycine sulphate (VI) dihydrate, the read-across hypothesis considers that source and target compounds have the same structural features related to “Aliphatic amines” (US EPA New Chemical Categories) and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. Based on the Dice measure, the structural similarity between analogues and the target compound was equal to 27.3%. The prediction was based on the monoethanolamine thioglycolate.
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. In case of structural similarity and toxic classification the information that “target chemical is out of domain” is caused by different alerts for the main core of the compound (Zn(Gly)SO4) and hydration water. Analogue search was based only on alerts for core of the target compound (Zn(Gly)SO4) which were exact the same as for source compound. Thus, information that “target chemical is out of domain” refers also to the alerts for hydration water and is not critical in this situation.
The structural similarity between the source (monoethanolamine thioglycolate) and the target compound Zn(Gly)SO4x2H2O equals to 27.3%.
GLP compliance:
no
Remarks:
QSAR

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
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw

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 target compound has the same structural features as source compound according to organic functional groups (US EPA) and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. The analogues search was performed assuming at least 20% structural similarity between the source and target substances. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Monoethanolamine thioglycolate would have the similar structural features (organic functional groups) and cause similar toxic effect (“High level” alert in Cramer profile) as well as the experimental data related to its acute dermal toxicity was available. Therefore, the prediction is based only on the monoethanolamine thioglycolate.