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In vitro Gene Mutation Study in Bacteria

In a GLP bacterial reverse mutation assay conducted in accordance with standardised guidelines OECD 471, EU Method B.13/14 and EPA OPPTS 870.5100, the genotoxicity of the test substance was determined. Four strains of S. typhimurium and one strain of E. coli were treated in the absence and presence of metabolic activation. Under the conditions of the test, no evidence of mutagenic activity in the bacterial system was observed and the test material was determined to be negative for genotoxicity.

In vitro Chromosome Aberration

The genotoxicity of the test material was investigated in a GLP study which was conducted in accordance with standardised guidelines OECD 473, EU Method B.10 and EPA OPPTS 870.5375 using Chinese hamster V79 lung cells. The study included two rangefinding cytotoxicity assays and three chomosome aberration assays. As the test material did not show repeatable induction of chromosome aberrations it was considered to be negative in this test.

In vitro Gene Mutation in Mammalian Cells

Dipotassium Heptafluorotantalate was evaluated for its ability to induce thymidine kinase gene mutations using the in vitro mammalian mouse lymphoma assay (MLA). The test laboratory indicated that the study was performed according to OECD Test Guideline TG476 (1997) and using Good Laboratory Practices. The acceptance criteria and the test interpretation criteria were indicated to be based on those of Moore et al, 2006; these criteria result from an international harmonization effort of the Mouse Lymphoma Expert Workgroup of the International Workshop for Genotoxicity Tests (IWGT). The test laboratory conducted several experiments and presented data for (1) two experiments with a 3 hour treatment with metabolic activation, (2) one experiment for a 3 hour treatment without metabolic activation, (3) and one experiment for a 24 hour treatment without metabolic activation.

The test laboratory concluded that Dipotassium Heptafluorotantalate was mutagenic with metabolic activation and not mutagenic in the absence of metabolic activation.  

There are, however, multiple issues that cast serious doubt on the positive results. These issues are summarized in the attached report (Comments on MLA for dipotassium heptafluorotantalate_final.pdf). It is recommended that the MLA study with Dipotassium Heptafluorotantalate be repeated to correct the deficiencies and to provide an appropriate evaluation as to whether it is actually mutagenic. This repeat study will be conducted with and without metabolic activation within 6 month after ECHAs draft decision on conducting an in vivo test was rejected (TPE-D-2114305085-61-01/D).

Justification for selection of genetic toxicity endpoint
As multiple studies are presented to address genetic toxicity, no one study was selected as the key study as they represent different types of genetic toxicity and are therefore not comparable.

Short description of key information:
In vitro Gene Mutation Study in Bacteria
Negative (with and without metabolic activation), OECD 471, EU Method B.13/B.14, EPA OPPTS 870.5100, Kitching (2001)

In vitro Chromosome Aberration
Negative (with and without metabolic activation), OECD 473, EU Method B.10, EPA OPPTS 870.5375, Hargitai (2013)

In vitro Gene Mutation in Mammalian Cells
Negative (without metabolic activation); Positive (with metabolic activation), OECD 476, EU Method B.17, Hargitai (2013)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with with criteria for classification and labelling as defined in Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD), the substance does not require classification for genetic toxicity.