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Key value for chemical safety assessment

Additional information

The genotoxic potential of RDP was investigated in three in vitro study and one in vivo study.

 

To determine the ability for gene mutation in bacteria, the Salmonella/microsome plate (, OECD471) test was performed, in the absence and presence of a metabolic activation system (S9-mix). The test substance did not induce a dose-related increase in the number of revertant (His+) colonies in each of the four test strains (S. typhimurium TA1535, TA1537, TA98, and TA100). These results were confirmed in an independently repeated experiment. The test substance can, therefore, be considered as not mutagenic in this test system.

 

Cytogenicity of the test substance was studied in both an in vitro and an in vivo study. In vitro, the induction of chromosome aberrations in cultured peripheral human lymphocytes was tested in the presence and absence of a metabolic activation system (S9-mix), according to OECD Guideline 473, 1983. None of the tested concentrations induced a statistically and biologically significant increase in the number of cells with chromosome aberrations, neither in the absence nor in the presence of S9-mix. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations. It is concluded that the test substance is not clastogenic in human lymphocytes under the experimental conditions described in this report.

The potential mutagenicity of Fyrolflex RDP on the thymidine kinase TK+/- was assessed according to OECD test guideline 476. The test item did not induce any toxicologically significant dose-related (linear trend) increase in the mutant frequency at any of the dose levels, either with or without metabolic activation, in either the first or second experiment. The vehicle control (DMSO) had mutant frequency values that were considered acceptable for LY5178Y cell line at the TK+/- locus. The positive control treatments induced marked increase in the mutant frequency indicating satisfactory performance of the test and of the activity of the metabolizing system. The test item is therefore considered to be non-mutagenic under the conditions of the test.

In the in vivo Micronucleus Test in mice, which was performed according to OECD guideline 474, the test substance was tested in three groups, each comprising 5 males and 5 females, receiving a single oral dose of 5000 mg/kg bw. Bone marrow was sampled at 24, 48 and 72 hours after dosing. Corresponding vehicle (Corn oil) treated groups served as negative controls. No increase in the frequency of micronuclei was observed, whereas the positive control substance (CP) produced a statistically significant increase in the incidence of micronuclei in polychromatic erythrocytes. It is concluded that RDP can be considered as not mutagenic in the Mouse Micronucleus Test, under the experimental conditions described in this report.


Short description of key information:
In vitro:
In vitro gene mutation in bacteria – Ames test (OECD Guideline 471 with deviations): not mutagenic
In vitro cytogenicity – Mammalian Chromosome aberration test (OECD Guidelines 473): not mutagenic
In vitro mammalian cell gene mutation - Mouse Lymphoma assay (OECD Guidelines 476): not mutagenic

In vivo:
In vitro cytogenicity - Micronucleus Test, mouse, (OECD Guideline 474): not mutagenic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

RDP did not show any genotoxic potential in the available in vitro and in vivo studies. Therefore it can be concluded that the substance is not mutagenic and does not need to be classified for mutagenicityaccording to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC), and outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).