Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a bacterial reverse gene mutation assay (OECD 471) it was not possible to solve the target substance Ytterbium stabilized Zirconium and Hafnium oxide in any of the solvents used (Aqua dest., DMSO, ethanol and acetone). Since the test item could not be prepared in an appropriate solvent and diluted prior to treatment, it was not possible to perform an Ames test with Ytterbium stabilized Zirconium and Hafnium oxide. The insolubility of the target substance was confirmed by a Transformation/dissolution assay (see IUCLID section 4.8). Hafnium and zirconium was not detectable. For ytterbium, an average metal release of 0.069 µg/L was measured after 7 days at 100 mg/L mass loading. To evaluate the bio-accessibility of the target substance a bio-elution test was conducted (see IUCLID section 7.1.1). The highest metal release values were found in artificial lysosomal fluid with a metal release for Yb of 8.314 µg/L, for Zr of 4.30 µg/L and for Hf of 0.02 µg/L (which is actually the limit of quantification). For the oral and dermal route, the metal release of hafnium was below the detection limit, for Yb within the range of 0.485 to 3.24 µg/L and for Zr within 0.01-0.02 µg/mL. Thus, the bioavailability of the target substance can be expected to very low. For the reasons presented and in line with REACH Annex XI, section 2, conducting an in vitro cytogenicity study and mutagenicity study in mammalian cells can be considered as technically not possible due to the very low solubility of the target substance.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-12-11 to 2018-02-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
Adopted 21st July, 1997
Deviations:
yes
Remarks:
Concerning preparation of the test Item
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Name: Ytterbium stabilized Zirconium and Hafnium Oxide
EC No.: 945-888-9
Batch No.: 7170502
Physical State: solid
Colour: white
Purity: > 95%
Expiry Date: 26 October 2022
Storage Conditions: room temperature, in a tightly closed container in a dry place
Target gene:
Histidine locus
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9
Species / strain:
S. typhimurium, other: TA98, TA100, TA102, TA1535 and TA1537
Metabolic activation:
not applicable
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
not examined
Untreated negative controls validity:
not examined
Positive controls validity:
not examined
Additional information on results:
The test item was checked for solubility in Aqua dest., DMSO, ethanol and acetone. Due to the properties of the test item, the material precipitated immediately with all solvents tested. Thus, no suspension, suitable for the dilution series could be obtained. Therefore, due to the insolubility of the test item, it was not possible to perform any further steps with the test item in this study.
Remarks on result:
not measured/tested
Conclusions:
Ytterbium stabilized Zirconium and Hafnium Oxide was not soluble in any of the solvents used. Therefore, it was not possible to perform an Ames test.
Executive summary:

In this study, the test item Ytterbium stabilized Zirconium and Hafnium oxide (target substance) could not be prepared in an appropriate solvent and diluted prior to treatment. Due to the properties of the material, the target substance was not soluble in any of the solvents used (Aqua dest., DMSO, ethanol and acetone). No stable suspension which is suitable for the preparation of the dilution series could be obtained. Therefore, it was not possible to perform any further steps in this study. Since the test item could not be prepared in an appropriate solvent and diluted prior to treatment, it was not possible to perform an Ames test with Ytterbium stabilized Zirconium and Hafnium oxide.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint:
in vitro gene mutation study in mammalian cells
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

In a bacterial reverse gene mutation assay (OECD 471) it was not possible to solve the target substance Ytterbium stabilized Zirconium and Hafnium oxide in any of the solvents used (Aqua dest., DMSO, ethanol and acetone). No stable suspension which is suitable for the preparation of the dilution series could be obtained. Therefore, it was not possible to perform any further steps in this study. Since the test item could not be prepared in an appropriate solvent and diluted prior to treatment, it was not possible to perform an Ames test with Ytterbium stabilized Zirconium and Hafnium oxide. The insolubility of the target substance was confirmed by a Transformation/dissolution assay (see IUCLID section 4.8). Hafnium and zirconium was not detectable. For ytterbium, an average metal release of 0.069 µg/L was measured after 7 days at 100 mg/L mass loading. To evaluate the bio-accessibility of the target substance a bio-elution test was conducted (see IUCLID section 7.1.1). The highest metal release values were found in artificial lysosomal fluid with a metal release for Yb of 8.314 µg/L, for Zr of 4.30 µg/L and for Hf of 0.02 µg/L (which is actually the limit of quantification). For the oral and dermal route, the metal release of hafnium was below the detection limit, for Yb within the range of 0.485 to 3.24 µg/L and for Zr within 0.01-0.02 µg/mL. Thus, the bioavailability of the target substance can be expected to very low. For the reasons presented and in line with REACH Annex XI, section 2, conducting an in vitro cytogenicity study and mutagenicity study in mammalian cells can be considered as technically not possible due to the very low solubility of the target substance. In addition, none of the released metals (Yb, Zr and Hf) are known to have any genotoxic potential (e.g. C&L inventory). Based on the assessment of the available data, no classification for genotoxicity is warranted for the target substance.