Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

1.     Bacterial Reverse Mutation, Ames test (Hazleton Laboratories America, 2001)

A bacterial reverse mutation test was conducted according to EU test method B13/14. Four mutant strains of Salmonella Typhimurium ( TA98, TA100, TA1535, TA1537, TA 1538) and Escherichia coli WP2uvrA- were exposed to T-1540N (applied as a solution in Dimethylsulphoxide). Concentration levels were 100 to 5000 µg/plate. The test was conducted with and without metabolic activation. No indication of mutagenic potential was seen at any concentration level, with or without metabolic activation, in any of the bacterial strains tested. The test material was cytotoxic >5000 µg/plate.

 

2.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Corning Hazleton Laboratories, 2001)

An assay using Human lymphocyte cells was conducted according to EU test method B10. The test material was applied as a solution in DMSO; the test were conducted between 28.13 micrograms/mL and 50µg/mL with and without metabolic activation. The test material showed signs of cytotoxicity >50µg/mL and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.

 

3.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Safepharm Laboratories Ltd, 2001)

An assay using Chinese Hamster lung cells was conducted according to EU test method B10. The test material was applied as a solution in DMSO; the tests were conducted between: 120.63 and 1930 µg/ml (with metabolic activation) and 1.89 and 30.16 µg/ml (without metabolic activation). The test material showed signs of cytotoxicity > 1930 µg/ml (with metabolic activation) and >30.16 µg/ml (without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.

 

4.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Safepharm Laboratories Ltd, 2001)

An assay using Chinese Hamster lung cells was conducted according to EU test method B10. The test material was applied as a solution in DMSO; the tests were conducted between: 241.25 and 1930 µg/ml (with metabolic activation) and 3.75 and 30 µg/ml (without metabolic activation). The test material showed signs of cytotoxicity > 1930 µg/ml (with metabolic activation) and 20 µg/ml (without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.

 

5.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Safepharm Laboratories Ltd, 2001)

An assay using Chinese Hamster lung cells was conducted according to EU test method B10. The test material was applied as a solution in DMSO; the tests were conducted between: 447.5 and 3580 µg/ml (with metabolic activation) and 55.94 and 1790 µg/ml (without metabolic activation). The test material showed signs of cytotoxicity > 3580 µg/ml (with metabolic activation) and 335.63 µg/ml (without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.

6.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Hita research Laboratories Ltd, 2001)

An assay using Chinese Hamster lung cells was conducted according to EU test method B10. The test material was applied as a solution in DMSO; the tests were conducted between: 50 and 5000 µg/ml (with metabolic activation) and 62.5 and 500 µg/ml (without metabolic activation). The test material showed signs of cytotoxicity 300µg/ml (with metabolic activation) and 200 µg/ml (without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.A dose-related increase in polyploidy was noted during this study in the presence and absence of metabolic activation. However, no aneuploidy or structural aberrations were observed.

 

7.     In vitro mammalian cytogenicity (B10)-Chromosone Aberration test (Corning Hazleton Laboratories Ltd, 2001)

An assay using Human peripheral blood lymphocytes was conducted according to OECD guideline 473, EU test method B10. The test material was applied as a solution in DMSO; the tests were conducted between: 3 and 50 µg/ml (with and without metabolic activation). The test material showed signs of cytotoxicity >50µg/ml (with and without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.

 

8.     Mammalian Cell gene mutation test (B17) (Corning Hazleton Laboratories Ltd, 2001). An assay using Mouse lymphoma L5178Y calls was conducted according to EU test method B17. The test material was applied as a solution in DMSO; the tests were conducted between: 6 and 50 µg/ml (with and without metabolic activation). The test material showed signs of cytotoxicity >50µg/ml (with and without metabolic activation) and did not demonstrate any mutagenic potential under the experimental conditions with and without metabolic activation.


Short description of key information:
Bacterial reverse Mutation, Ames test- negative for genetic mutation, with and without metabolic activation.
In vitro Mammalian Chromosone aberration test-negative for genetic mutation, with and without metabolic activation.
In vitro Mamalian cell gene mutation test-negative for genetic mutation, with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All studies conducted for genetic toxcity included one Ames test, six Chromosone Aberration tests and one In vitro Mamalian cell gene mutation test. As all studies gave a negative result it was concluded that the test material T-1540N showed no signs of mutagenic potential.