zinc glycyniate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

The short-term in vitro mammalian cell chromosome aberration test is used to assess potential genotoxic hazard of the test substance.
The aim was to estimate the cytogenicity of target substance by in vitro mammalian chromosome aberration test.

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 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 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. Four compounds that met this requirement (and were tested according to the recommended OECD 473 guideline)
According to the worst-case scenario and the highest structural similarity, CoSO4 analogue was used as the source compound.
The chromosome aberration for the source compound was performed according to:
Test guideline: OECD 473
Endpoint: chromosome aberration
Test organism: Mammalian cells
“One to one” read-across approach was used to predict the cytogenicity of target substance expressed by in vitro mammalian chromosome aberration test.

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 in vitro cytogenicity 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%. Four compounds met this requirement (and were tested according to the recommended OECD 473 guideline). According to the worst-case scenario and the highest structural similarity, CoSO4 analogue 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 (CoSO4) and the target compound Zn(Gly)SO4x2H2O equals to 42.1%

Species / strain:

mammalian cell line, other:

Metabolic activation:

not specified

Genotoxicity:

other:

Remarks:

QSAR

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The in vitro mammalian chromosome aberration for the target substance is predicted as positive.

Additional information on results:

The in vitro mammalian chromosome aberration for the target substance is predicted as positive.

Remarks on result:

ambiguous mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

The in vitro mammalian chromosome aberration for the target substance is predicted as positive.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Justification for type of information:

The in vitro mammalian gene mutation cells can be used to detect gene mutation induced by chemical substances.
The aim was to estimate the gene mutation (in vitro mammalian cell gene mutation) of target substance.
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 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 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. Five compounds that met this requirement (and were
tested according to the recommended OECD 476 guideline) were found, Table 5. According to the worst-case scenario, the highest structural similarity and the transition metal character, CoSO4 analogue was used as the source compound.
The gene mutation for the source compound was performed according to:
Test guideline: OECD 476
Endpoint: Gene mutation
Test organism: Mammalian cells
The read-across prediction of the gene mutation for the target substance was performed based on the “one to one” approach.

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 in vitro gene mutation 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%. Five compounds met this requirement (and were tested according to the recommended OECD 476 guideline). According to the worst-case scenario and the highest structural similarity, CoSO4 analogue 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 (CoSO4) and the target compound Zn(Gly)SO4x2H2O equals to 42.1%

Species / strain:

mammalian cell line, other:

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

The gene mutation for the target substance is predicted as negative.

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. Cobalt (II) sulphate would have similar dissociation products (H2SO4 and Co(OH)2) as well as the experimental data related to its in vitro gene mutation was available. Therefore, the prediction

is based only on the CoSO4.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Based on the results obtained under the experimental conditions applied, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
In conclusion, the test item ZINC GLYCINATE has no mutagenic activity in the bacterial tester strains under the test conditions used in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

no classified