Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

AmesTest                                                                                                              

 An Ames test was performed to investigate the mutagenic potential of the test item according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the S. typhimurium strains TA 1535, TA 1537, TA98, and TA 100, and the E. coli strain WP2 uvrA (OECD guideline 471). The assay was performed in two independent experiments both with and without metabolic activation at concentrations of 33; 100; 333; 1000; 2500; and 5000 µg/plate. The test article had no effect on the number of revertant colonies and it is concluded that under the conditions of this test, the substance did not induce gene mutantions.

Chromosome aberrations                                                                                             

 Chinese hamster cells (V79) were used to determine the potential of the test item to induce chromosomal aberrations in presence and absence of a metabolic activation system (OECD guideline 473). The cells were exposed for 4h to dose levels of 18.8 – 300 µg/plate in two parallel cultures. Per culture 100 metaphase plates were scored for aberrations. The number of aberrations was significantly increased at concentrations of 150 µg/plate without S9 mix and at 18.8 and 75 µg/plate with S9 mix. Substance dose level of 75 and 150 µg/plate induced also strong cytotoxicity and a non-genotoxic DNA-damage cannot be excluded.

HPRT assay

The test substance was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro. Three independent experiments were carried out, with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation). According to an initial range-finding cytotoxicity test for the determination of the experimental doses and taking into account the cytotoxicity actually found in the main experiments, a dose range from 3.13 - 300 ug/ml was tested in this study (4h or 24h exposure period). Concentrations from 6.25 - 120 ug/ml maximum were evaluated. Cytotoxicity was observed at the highest dose level. The test item did not cause any relevant increase in the mutant frequencies either without S9 mix or after adding a metabolizing system.

Micronucleus assay in mouse                                                                                 

The test item, dissolved in corn oil, was administrated at concentrations of 200 – 2000 mg/kg bw orally to groups of 5 male and female mice (OECD guideline 474).24 h and 48 h after administration the bone marrow cells were collected for micronuclei analysis; 2000 polychromatic erythrocytes per animal were scored. The frequency of detected micronuclei was not enhanced at any dose level and it is concluded that the test substance did not induce micronuclei in vivo.


Short description of key information:
Valid in vitro and in vivo studies assessing genotoxicity of the test substance are available. In an Ames test conducted according to OECD 471 and in an HPRT assay according OECD guideline 476 no mutagenicity was seen. In an in vitro chromosome aberration assay conducted according to OECD guideline 471 an increase in structural chromosome aberrations was seen only at concentrations which also induced strong cytotoxicity. In an in vivo Micronucleus test according to OECD guideline 474 no increased incidence of micronuclei in bone marrow cells of the mouse was seen. Based on results of these studies the test substance was considered to be not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for genotoxicity under Directive 67/548/EEC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genotoxicity under Regulation (EC) No. 1272/2008.